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Undiagnosed metabolic disorders v1.640 CPOX Ida Ertmanska Mode of inheritance for gene: CPOX was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.637 CPOX Ida Ertmanska changed review comment from: Comment on mode of inheritance: As reviewed by Sharon Whatley, variants in CPOX may cause autosomal dominant or autosomal recessive porphyria. Biallelic variants tend to cause earlier onset and more severe symptoms. Hence, the MOI should be changed from 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal'.
CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 20th Oct 2025).; to: Comment on mode of inheritance: As reviewed by Sharon Whatley, variants in CPOX may cause autosomal dominant or autosomal recessive porphyria. Monoallelic variants in CPOX have very low clinical penetrance (<1%) and may be challenging to report as diagnostic. Hence, BIALLELIC, autosomal or pseudoautosomal MOI would be more appropriate.
CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 20th Oct 2025).
Undiagnosed metabolic disorders v1.637 CPOX Ida Ertmanska edited their review of gene: CPOX: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.637 CPOX Ida Ertmanska Mode of inheritance for gene CPOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.636 CPOX Ida Ertmanska Tag Q3_25_MOI was removed from CPOX.
Undiagnosed metabolic disorders v1.635 CPOX Ida Ertmanska Phenotypes for gene: CPOX were changed from Hereditary coproporphyria (Acute neuropathic porphyrias); Coproporphyria 121300; Harderoporphyria 121300 to Coproporphyria, OMIM:121300; Harderoporphyria, OMIM:618892
Publications for gene: CPOX were updated from 27604308 to 6886003; 7757079; 8012360; 9454777; 10505225; 11074238; 11309681; 16159891; 21103937; 23236641; 23605133; 30828546; 33008663; 37540847; 38940544; 40296768
Tag Q3_25_MOI tag was added to CPOX.
Undiagnosed metabolic disorders v1.634 CPOX Ida Ertmanska reviewed gene: CPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 6886003, 7757079, 8012360, 9454777, 10505225, 11074238, 11309681, 16159891, 21103937, 23236641, 23605133, 30828546, 33008663, 37540847, 38940544, 40296768; Phenotypes: Coproporphyria, OMIM:121300, Harderoporphyria, OMIM:618892; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.632 CPOX Sharon Whatley reviewed gene: CPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38940544, 11309681, 37540847, 23236641, 11074238, 23605133, 16159891, 40296768, 33008663, 30828546, 21103937, 16159891, 10505225, 9454777, 7757079, 8012360, 6886003; Phenotypes: 121300, 618892; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.631 PPOX Sharon Whatley changed review comment from: Relevant metabolic investigation: urine porphobilinogen and plasma porphyrin fluorescence emission
PMID: 38940544 Aarsand reports that the acute porphyrias are a group of rare inborn errors of metabolism caused by abnormal functioning of haem biosynthesis enzymes and are associated with acute neurovisceral attacks characterized by severe abdominal pain and neuropsychiatric symptoms that may require highly specialized intensive care. The acute porphyrias, acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP), usually become symptomatic in early adulthood.
PMID: 10486317 Whatley found that skin lesions were the only manifestation of VP in 59% of patients whereas 21% of patients had acute attacks and skin lesions. The remainder having only acute attacks.
PMID: 8290408 Hift reports that the cutaneous VP presents with photosensitivity which may result in blistering, erosions, a fragile skin with chronic scarring and pigmentary changes
PMID: 38940544 Aarsand reports that VP is an autosomal dominant disorder and estimates that individuals with a predisposition for VP in the general population is 1/3,000 (except where founder effects occur e.g. South Africa). A rough estimate of the penetrance of pathogenic variants in this gene is given as 1%. Due to this low penetrance, genetic testing alone may be misleading and cause misdiagnosis. IPNET advises that VP is diagnosed using biochemical tests (urine porphobilinogen during an acute attack followed by plasma porphyrin fluorescence emission or if the patient only has cutaneous symptoms plasma porphyrin fluorescence emission) as the penetrance of variegate porphyria is so low
PMID: 37879139 Assaleh reports that biallelic VP is rare. To the best of our knowledge there are 25 patients (in 21 families) reported with homozygous VP (PMID: 40114189 Kaiser, 37879139 Assaleh, 33159949 Cho and references therein). It usually presents in infancy with severe cutaneous manifestations. In some cases, patients may have hand deformities, nystagmus, growth delay and intellectual disability.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the PPOX gene, due to its low clinical penetrance.; to: Relevant metabolic investigation: urine porphobilinogen and plasma porphyrin fluorescence emission
PMID: 38940544 Aarsand reports that the acute porphyrias are a group of rare inborn errors of metabolism caused by abnormal functioning of haem biosynthesis enzymes and are associated with acute neurovisceral attacks characterized by severe abdominal pain and neuropsychiatric symptoms that may require highly specialized intensive care. The acute porphyrias, acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP), usually become symptomatic in early adulthood.
PMID: 10486317 Whatley found that skin lesions were the only manifestation of VP in 59% of patients whereas 21% of patients had acute attacks and skin lesions. The remainder having only acute attacks.
PMID: 8290408 Hift reports that the cutaneous VP presents with photosensitivity which may result in blistering, erosions, a fragile skin with chronic scarring and pigmentary changes
PMID: 38940544 Aarsand reports that VP is an autosomal dominant disorder and estimates that individuals with a predisposition for VP in the general population is 1/3,000 (except where founder effects occur e.g. South Africa). A rough estimate of the penetrance of pathogenic variants in this gene is given as 1%. Due to this low penetrance, genetic testing alone may be misleading and cause misdiagnosis. IPNET advises that VP is diagnosed using biochemical tests (urine porphobilinogen during an acute attack followed by plasma porphyrin fluorescence emission or if the patient only has cutaneous symptoms plasma porphyrin fluorescence emission) as the penetrance of VP is so low
PMID: 37879139 Assaleh reports that biallelic VP is rare. To the best of our knowledge there are 25 patients (in 21 families) reported with homozygous VP (PMID: 40114189 Kaiser, 37879139 Assaleh, 33159949 Cho and references therein). It usually presents in infancy with severe cutaneous manifestations. In some cases, patients may have hand deformities, nystagmus, growth delay and intellectual disability.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the PPOX gene, due to its low clinical penetrance.
Undiagnosed metabolic disorders v1.508 CPT2 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI was updated from 'Biallelic' to 'Both mono- and biallelic'. Although most cases are associated with biallelic variants, symptomatic heterozygous patients have also been described (PMID: 15622536; 21913903; 23184072; 24843804). Severity of symptoms tends to correlate with residual CPT enzyme activity but it is plausible that heterozygotes may still be tested under this panel. Both MOIs are listed in OMIM for this phenotype (MIM# 255110)
Undiagnosed metabolic disorders v1.508 CPT2 Arina Puzriakova Mode of inheritance for gene: CPT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.507 CPT2 Arina Puzriakova Publications for gene: CPT2 were set to 27604308; 24816252
Undiagnosed metabolic disorders v1.506 CPT2 Arina Puzriakova Phenotypes for gene: CPT2 were changed from Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle); CPT deficiency, hepatic, type II 600649; CPT II deficiency, lethal neonatal 608836 to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836; CPT II deficiency, myopathic, stress-induced, OMIM:255110; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle)
Undiagnosed metabolic disorders CP Sarah Leigh marked CP as ready
Undiagnosed metabolic disorders CP Sarah Leigh classified CP as green
Undiagnosed metabolic disorders CPOX Ellen McDonagh reviewed CPOX
Undiagnosed metabolic disorders CPT2 Arianna Tucci reviewed CPT2
Undiagnosed metabolic disorders CP Sarah Leigh edited their review of CP
Undiagnosed metabolic disorders CP Sarah Leigh edited their review of CP
Undiagnosed metabolic disorders CP Sarah Leigh edited their review of CP
Undiagnosed metabolic disorders CP Sarah Leigh reviewed CP