Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
33 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.80 | PPOX |
Achchuthan Shanmugasundram changed review comment from: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with disease onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions, along with neurologic and/ or neurodevelopmental symptoms: nystagmus, epileptic seizures, developmental delay, intellectual disability, and sensory neuropathy (PMIDs: 8290408; 9811936; 2004012; 35164799; 37879139; 40114189). PPOX is associated with AD Variegate porphyria (176200) and AR Variegate porphyria, childhood onset (620483) in OMIM - accessed 13th October 2025. Hence, the mode of inheritance should be set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' on this panel.; to: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with disease onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions, along with neurologic and/ or neurodevelopmental symptoms: nystagmus, epileptic seizures, developmental delay, intellectual disability, and sensory neuropathy (PMIDs: 8290408; 9811936; 2004012; 35164799; 37879139; 40114189). PPOX is associated with AD Variegate porphyria (176200) and AR Variegate porphyria, childhood onset (620483) in OMIM - accessed 28th October 2025. Hence, the mode of inheritance should be set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' on this panel. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: Comment on list classification: There are at least 7 unrelated individuals with biallelic variants in ACOX2, presenting with persistent elevation of transaminase levels and C27 intermediate bile acids. 2 patients had liver fibrosis and developmental delay. Based on the available evidence, this gene should be rated Green for Likely inborn error of metabolism.; to: Comment on list classification: There are at least 7 unrelated individuals with biallelic variants in ACOX2, presenting with persistent elevation of transaminase levels and C27 intermediate bile acids. 2 patients had liver fibrosis and developmental delay. The association is supported by a mouse model, where Acox2 knockout resulted in elevated hepatic transaminases, liver fibrosis and hepatic inflammation. Based on the available evidence, this gene should be rated Green for Likely inborn error of metabolism. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 | Ida Ertmanska commented on gene: ACOX2: Comment on list classification: There are at least 7 unrelated individuals with biallelic variants in ACOX2, presenting with persistent elevation of transaminase levels and C27 intermediate bile acids. 2 patients had liver fibrosis and developmental delay. Based on the available evidence, this gene should be rated Green for Likely inborn error of metabolism. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This variants seems to be associated with a mild phenotype. PMID: 29287774 Ferdinandusse et al., 2018 Report of a girl of Pakistani origin, consanguineous parents. Homozygous for a 4-nucleotide deletion in ACOX2: c.461-464delTCTG (p.Thr154Serfs*25). Presented at birth with thoracolumbar scoliosis, arthrogryposis, neuropathy and myopathy. Patient died at around 6 months, after intensive support was withdrawn. Disproportionate increase of the peroxisomal C27-bile acid intermediates was observed. Absence of ACOX2 protein in patient's fibroblast homogenate was shown by immunoblot. Seq method: panel 26 peroxisomal genes - other variants likely contributed to the severity of the phenotype in this patient. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This variants seems to be associated with a mild phenotype. PMID: 29287774 Ferdinandusse et al., 2018 Report of a girl of Pakistani origin, consanguineous parents. Homozygous for a 4-nucleotide deletion in ACOX2: c.461-464delTCTG (p.Thr154Serfs*25). Presented at birth with thoracolumbar scoliosis, arthrogryposis, neuropathy and myopathy. Patient died at around 6 months, after intensive support was withdrawn. Disproportionate increase of the peroxisomal C27-bile acid intermediates was observed. Absence of ACOX2 protein in patient's fibroblast homogenate was shown by immunoblot. Seq method: panel 26 peroxisomal genes - other variants likely contributed to the severity of the phenotype in this patient. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This variants seems to be associated with a mild phenotype. PMID: 29287774 Ferdinandusse et al., 2018 Report of a girl of Pakistani origin, consanguineous parents. Homozygous for a 4-nucleotide deletion in ACOX2: c.461-464delTCTG (p.Thr154Serfs*25). Presented at birth with thoracolumbar scoliosis, arthrogryposis, neuropathy and myopathy. Patient died at around 6 months, after intensive support was withdrawn. Disproportionate increase of the peroxisomal C27-bile acid intermediates was observed. Absence of ACOX2 protein in patient's fibroblast homogenate was shown by immunoblot. Seq method: panel 26 peroxisomal genes - other variants likely contributed to the severity of the phenotype in this patient. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This variants seems to be associated with a mild phenotype. PMID: 29287774 Ferdinandusse et al., 2018 Report of a girl of Pakistani origin, consanguineous parents. Homozygous for a 4-nucleotide deletion in ACOX2: c.461-464delTCTG (p.Thr154Serfs*25). Presented at birth with thoracolumbar scoliosis, arthrogryposis, neuropathy and myopathy. Patient died at around 6 months, after intensive support was withdrawn. Disproportionate increase of the peroxisomal C27-bile acid intermediates was observed. Absence of ACOX2 protein in patient's fibroblast homogenate was shown by immunoblot. Seq method: panel 26 peroxisomal genes - other variants likely contributed to the severity of the phenotype in this patient. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This variants seems to be associated with a mild phenotype. PMID: 29287774 Ferdinandusse et al., 2018 PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This variants seems to be associated with a mild phenotype. PMID: 29287774 Ferdinandusse et al., 2018 Report of a girl of Pakistani origin, consanguineous parents. Homozygous for a 4-nucleotide deletion in ACOX2: c.461-464delTCTG (p.Thr154Serfs*25). Presented at birth with thoracolumbar scoliosis, arthrogryposis, neuropathy and myopathy. Patient died at around 6 months, after intensive support was withdrawn. Disproportionate increase of the peroxisomal C27-bile acid intermediates was observed. Absence of ACOX2 protein in patient's fibroblast homogenate was shown by immunoblot. Seq method: panel 26 peroxisomal genes - other variants likely contributed to the severity of the phenotype in this patient. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This variants seems to be associated with a mild phenotype. PMID: 29287774 Ferdinandusse et al., 2018 PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. Case 3: 15yo male, Spanish; presented with abdominal distension, steatorrhea, and hypertransaminasemia with childhood onset; liver biopsy showed slight fibrosis. Compound het for c.673C>T, p.(Arg225Trp) and c.456_459del, p.(Thr154Serfs*25). Het parents unaffected. Case 4: 7yo boy; presented with congenital heart disease (mild mitral stenosis, and moderate‐severe aortic insufficiency) with slight developmental delay and oscillating hypertransaminasemia. Compound het: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). Elevated C27‐BA proportion, treated with UDCA. Zhang Y, et al., 2021, PMID: 33340570: ACOX2 KO mice had elevated hepatic transaminases, liver fibrosis and hepatic inflammation. The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. PMID: 35395098 Alonso-Pena et al., 2022 c.673C>T (p.Arg225Trp) was found in homozygosity in two patients (Case 1 & Case 2) with unexplained hypertransaminasemia. Impaired liver expression of ACOX2 was found by immunohistochemistry. Hypertransaminasemia was successfully treated with UDCA. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Method: Exome sequencing. Patient presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025).; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 The clinical presentation may be variable, but all reported probands to date have had elevated serum C27 bile acid intermediates, consistent with loss of ACOX2 enzyme activity Three variants (missense, nonsense, frameshift) that have been reported in six probands in three publications (PMID: 27647924, 27884763, 35395098) are included in this publication. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). Based on the available genetic and experimental evidence, the association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). ; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 16yo male with persistent hypertransaminasemia, homozygous for c.673C>T; R225W. Patient's serum and urine showed negligible amounts of C24 bile acids, but augmented levels of C27 intermediates. Liver histology was normal. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). The association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). The gene is also associated with Bile acid synthesis defect, congenital, 6, 617308 in OMIM (accessed 15th Oct 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. The clinical presentation may be variable, but all reported probands to date have had elevated serum C27 bile acid intermediates, consistent with loss of ACOX2 enzyme activity. Three variants (missense, nonsense, frameshift) that have been reported in six probands in three publications (PMID: 27647924, 27884763, 35395098) are included in this publication. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). Based on the available genetic and experimental evidence, the association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). ; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. PMID:27884763 Monte et al., 2017 The clinical presentation may be variable, but all reported probands to date have had elevated serum C27 bile acid intermediates, consistent with loss of ACOX2 enzyme activity Three variants (missense, nonsense, frameshift) that have been reported in six probands in three publications (PMID: 27647924, 27884763, 35395098) are included in this publication. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). Based on the available genetic and experimental evidence, the association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v8.62 | ACOX2 |
Ida Ertmanska changed review comment from: The clinical presentation may be variable, but all reported probands to date have had elevated serum C27 bile acid intermediates, consistent with loss of ACOX2 enzyme activity. Three variants (missense, nonsense, frameshift) that have been reported in six probands in three publications (PMID: 27647924, 27884763, 35395098) are included in this publication. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). Based on the available genetic and experimental evidence, the association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). Sources: Other, ClinGen; to: PMID: 27647924 Vilarinho et al., 2016 8-y-old Turkish male from a consanguineous family. Homozygous for NM_003500.4(ACOX2):c.207T>A (p.Tyr69Ter). Presented with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Proband’s plasma and urine had strikingly elevated levels of the C27 intermediate bile acids. Absence of ACOX2 in the proband’s liver demonstrated using immunohistochemistry. The clinical presentation may be variable, but all reported probands to date have had elevated serum C27 bile acid intermediates, consistent with loss of ACOX2 enzyme activity. Three variants (missense, nonsense, frameshift) that have been reported in six probands in three publications (PMID: 27647924, 27884763, 35395098) are included in this publication. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by in vitro functional assays, biochemical function, and an animal model (PMID: 8387517, 8943006, 29287774, 33736801, 31533369, 33340570, 35395098). Based on the available genetic and experimental evidence, the association between ACOX2 and autosomal recessive congenital bile acid synthesis defect 6 has been classified as Definitive in ClinGen (July 2024). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v4.114 | VPS16 |
Sarah Leigh gene: VPS16 was added gene: VPS16 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Other Q4_23_promote_green tags were added to gene: VPS16. Mode of inheritance for gene: VPS16 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS16 were set to 33938619; 34013567 Phenotypes for gene: VPS16 were set to Mucopolysaccharidosis-like syndrome (biallelic); Dystonia Associated with Lysosomal Abnormalities (monoallelic); Dystonia 30, OMIM:619291 Review for gene: VPS16 was set to GREEN Added comment: Copied from Lysosomal storage disorder panel: Four individuals from three families were identified (PMIDs: 33938619; 34013567) exhibiting a mucopolysaccharidosis (MPS)-like lysosomal storage phenotype with short stature, coarse facies, DD or regression, peripheral neuropathy, skeletal dysplasia, neutropenia, and high-normal glycosaminoglycan excretion. All harboured homozygous variants in VPS16 which segregated with disease, including a missense variant in a sib pair (c.540G>T; p.Trp180Cys) and a recurrent intronic variant (c.2272‐18C>A) in two supposedly unrelated patients (although both of Middle Eastern descent). Fibroblasts of the two patients with the intronic variant showed accumulation of lysosomal compartments and autophagosomes with significantly decreased VPS16 mRNA and protein levels, as well as HOPS/CORVET complexes. Cellular phenotypes were rescued upon re-expression of wild-type VPS16. ----- Heterozygous variants, as well as a homozygous missense variant (c.156C>A) found in a consanguineous Chinese family (PMID:27174565), have been found to cause dystonia with variable onset (OMIM:619291). It has been suggested that the discrepancies in patient phenotypes are due to different mechanisms of pathogenicity, where variants causing dystonia do not affect the levels of endolysosomal tethering (HOPS/CORVET) complexes. More research is needed to clarify the mechanisms underlying VPS16-related dystonia as only limited functional data is currently available - Steel et al. 2020 (PMID:32808683) did perform electron microscopic studies of lymphocytes and fibroblasts derived from 2 unrelated patients, which showed vacuolar abnormalities suggestive of impaired lysosomal function. Sources: Literature Arina Puzriakova (Genomics England Curator), 14 Jun 2021 Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v4.2 | SPG7 | Sarah Leigh edited their review of gene: SPG7: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.315 | UQCRC1 | Arina Puzriakova Added comment: Comment on list classification: Rating Amber based on current evidence - three unrelated individuals with Parkinson's disease and heterozygous variants identified by one group (PMID: 33141179) but results have failed to be replicated in large European and Chinese cohorts (PMIDs: 33779694; 33248804) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.262 | STT3A | Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from 'biallelic' to 'both mono- and biallelic' - congenital disorder of glycosylation due to STT3A has been identified in at least 3 families with biallelic variants (PMIDs: 23842455; 30701557; 28424003) and 9 families with monoallelic variants (PMID: 34653363) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.186 | EHHADH | Arina Puzriakova Phenotypes for gene: EHHADH were changed from L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine to ?Fanconi renotubular syndrome 3, OMIM:615605; L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.181 | ACAT2 | Arina Puzriakova Added comment: Comment on list classification: New gene added by Andžela Lazdāne. Currently associated with a provisional phenotype in OMIM (?ACAT2 deficiency, OMIM:614055) and not yet listed in G2P. In the 2 cases reported to date (PMIDs: 20597, 6150136), diagnoses were made based on molecular rather than genetic findings. Rating Red as at present there is no published evidence of deleterious variants in the ACAT2 gene leading to this phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.174 | SERAC1 | Arina Puzriakova Phenotypes for gene: SERAC1 were changed from Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome (MEGDEL) (Organic acidurias); 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739 to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739; Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.154 | EHHADH |
Andžela Lazdāne gene: EHHADH was added gene: EHHADH was added to Inborn errors of metabolism. Sources: Literature Mode of inheritance for gene: EHHADH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EHHADH were set to PMID: 33340416 Phenotypes for gene: EHHADH were set to L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine Review for gene: EHHADH was set to AMBER Added comment: Fanconi renotubular syndrome type 3. The EHHADH gene is included in international classification of inherited metabolic disorders (ICIMD), Disorders of peroxisomal fatty acid oxidation. IEM Nosology Group (IEMbase): Disorders of peroxisomal β-oxidation. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.147 | ALDH18A1 | Sarah Leigh commented on gene: ALDH18A1: The mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal, as reduced levels of proline, ornithine, arginine, and citrulline have been reported in cases with both monoallelic and biallelic ALDH18A1 variants (PMIDs 11092761; 22170564; 26320891). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v2.22 | AHCY | Arina Puzriakova Phenotypes for gene: AHCY were changed from S-adenosylhomocysteine hydrolase deficiency (Disorders of the metabolism of sulphur amino acids) to Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase, 613752; Disorders of the metabolism of sulphur amino acids | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.286 | SPTLC1 |
Catherine Snow changed review comment from: Promoted from Amber to Green. This gene is associated with a relevant disease in OMIM and there is enough evidence to support a gene-disease association. SPTLC1, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID 20097765 reports that mutations in SPTLC1 cause a gain of function mechanism, which results in the formation of two atypical and neurotoxic sphingolipid metabolites. Confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/) and in sufficient publications.; to: Promoted from Amber to Green. This gene is associated with a relevant disease in OMIM and there is enough evidence to support a gene-disease association. SPTLC1, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID 20097765 reports that mutations in SPTLC1 cause a gain of function mechanism, which results in the formation of two atypical and neurotoxic sphingolipid metabolites. Confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/) and in sufficient publications. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.281 | SPTLC2 |
Catherine Snow changed review comment from: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. SPTLC2, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID: 20920666 reports on three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families and also confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/). This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.; to: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. SPTLC2, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID: 20920666 reports on three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families and also confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/). This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.47 | IDS |
Ivone Leong Source NHS GMS was added to IDS. Source London North GLH was added to IDS. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v0.4 | TAZ |
Ellen McDonagh Added phenotypes Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Barth syndrome, 302060; Methylglutaconic aciduria type II, Barth syndrome (Organic acidurias); Disorders of mitochondrial lipid metabolism for gene: TAZ Publications for gene TAZ were changed from to 27604308 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v0.4 | IDS |
Ellen McDonagh gene: IDS was added gene: IDS was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: IDS were set to 27604308 Phenotypes for gene: IDS were set to MUCOPOLYSACCHARIDOSIS TYPE 2; MPS II, Hunter disease (Mucopolysaccharidoses); Mucopolysaccharidosis II, 309900; Mucopolysaccharidosis Type II |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v0.4 | ATAD3B |
Ellen McDonagh gene: ATAD3B was added gene: ATAD3B was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: ATAD3B was set to Unknown Phenotypes for gene: ATAD3B were set to Influence on AIDS progression; No OMIM phenotype |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v0.4 | SERAC1 |
Ellen McDonagh Added phenotypes Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome (MEGDEL) (Organic acidurias); 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739 for gene: SERAC1 Publications for gene SERAC1 were changed from 29205472 to 27604308 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v0.4 | AHCY |
Ellen McDonagh gene: AHCY was added gene: AHCY was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: AHCY was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AHCY were set to 27604308 Phenotypes for gene: AHCY were set to S-adenosylhomocysteine hydrolase deficiency (Disorders of the metabolism of sulphur amino acids) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v0.4 | AGK |
Ellen McDonagh Added phenotypes Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Mitochondrial DNA depletion syndrome 10; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Acylglycerol kinase deficiency (Senger syndrome) (Disorders of complex lipid synthesis); Sengers syndrome, 212350; Sengers syndrome 212350; Disorders of mitochondrial lipid metabolism; Cataract 38, autosomal recessive, 614691 for gene: AGK Publications for gene AGK were changed from to 27604308 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||