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Rare anaemia v3.13 CPOX Ida Ertmanska Tag Q3_25_expert_review was removed from gene: CPOX.
Rare anaemia v3.13 CPOX Ida Ertmanska Tag Q3_25_expert_review tag was added to gene: CPOX.
Rare anaemia v3.13 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia.

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12 - transient. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G p.(Asp233Gly) & c.1207_1218del12, p.(Thr403_Gly406del).

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Schmitt et al., 2005). The presentation does not usually include anaemia.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G p.(Asp233Gly) & c.1207_1218del12, p.(Thr403_Gly406del).

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).
Rare anaemia v3.13 CPOX Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: CPOX.
Rare anaemia v3.13 CPOX Achchuthan Shanmugasundram Classified gene: CPOX as Amber List (moderate evidence)
Rare anaemia v3.13 CPOX Achchuthan Shanmugasundram Gene: cpox has been classified as Amber List (Moderate Evidence).
Rare anaemia v3.12 CPOX Achchuthan Shanmugasundram 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
Rare anaemia v3.10 PPOX Ida Ertmanska changed review comment from: The review by Sharon Whatley (International Porphyria Network) was resubmitted on the Rare anaemia panel with CPOX as the gene name.; to: The review by Sharon Whatley (International Porphyria Network) was resubmitted on the Rare anaemia panel with CPOX as the gene name. PPOX variants do not appear to cause anaemia.
Rare anaemia v3.10 PPOX Ida Ertmanska changed review comment from: The review by Sharon Whatley (International Porphyria Network) was resubmitted with CPOX as the gene name.; to: The review by Sharon Whatley (International Porphyria Network) was resubmitted on the Rare anaemia panel with CPOX as the gene name.
Rare anaemia v3.10 CPOX Ida Ertmanska edited their review of gene: CPOX: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Comment on list classification: There at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance and it does not usually present with anaemia. Based on the available evidence, CPOX should be rated Green for Rare anaemia.; to: Comment on list classification: There at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance and it does not usually present with anaemia. Based on the available evidence, CPOX should be rated Green for Rare anaemia, with Mode of Inheritance set to BIALLELIC, autosomal or pseudoautosomal.
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia.

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G p.(Asp233Gly) & c.1207_1218del12, p.(Thr403_Gly406del).

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia.

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12 - transient. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G p.(Asp233Gly) & c.1207_1218del12, p.(Thr403_Gly406del).

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Comment on list classification: There at least 2 unrelated individuals with Coproporphyria harbouring monoallelic variants in CPOX, and at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance. Based on the available evidence, CPOX should be rated Green for Rare anaemia.; to: Comment on list classification: There at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance and it does not usually present with anaemia. Based on the available evidence, CPOX should be rated Green for Rare anaemia.
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia. 2 cases of Coproporphyria with anaemia have been reported:

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G p.(Asp233Gly) & c.1207_1218del12, p.(Thr403_Gly406del).

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia.

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G p.(Asp233Gly) & c.1207_1218del12, p.(Thr403_Gly406del).

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia. 2 cases of Coproporphyria with anaemia have been reported:

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia. 2 cases of Coproporphyria with anaemia have been reported:

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G p.(Asp233Gly) & c.1207_1218del12, p.(Thr403_Gly406del).

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia. 2 cases of Coproporphyria with anaemia have been reported:

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with symptoms of erythropoietic harderoporphyria (photosensitivity of the skin, hemolytic anemia, and jaundice). However, the pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. We found a heterozygous, novel, four-base pair deletion in exon 7 of the CPOX gene. patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia. 2 cases of Coproporphyria with anaemia have been reported:

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with photosensitivity of the skin, hemolytic anemia, and jaundice. Became anemic on day 9, but recovered spontaneously by day 12. The pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. Heterozygous for a deletion in exon 7 of the CPOX gene. Patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Comment on list classification: There at least 17 unrelated individuals with Coproporphyria harbouring monoallelic variants in CPOX, and at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance. Based on the available evidence, CPOX should be rated Green for Rare anaemia.; to: Comment on list classification: There at least 2 unrelated individuals with Coproporphyria harbouring monoallelic variants in CPOX, and at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance. Based on the available evidence, CPOX should be rated Green for Rare anaemia.
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005).
PMID: 11309681 Lamoril et al., 2001: 17 apparently unrelated patients diagnosed with Coproporphyria, of which 15 had reported heterozygous variants in CPOX. 13 patients have experienced acute attacks (with or without skin lesions), 4 patients have had no attacks- diagnosis was established by measurement of fecal porphyrin. Missense variants are the most common.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005). The presentation does not usually include anaemia. 2 cases of Coproporphyria with anaemia have been reported:

PMID: 28349448 Hasegawa et al., 2017
Report of a neonate with symptoms of erythropoietic harderoporphyria (photosensitivity of the skin, hemolytic anemia, and jaundice). However, the pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. We found a heterozygous, novel, four-base pair deletion in exon 7 of the CPOX gene. patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005).
PMID: 11309681 Lamoril et al., 2001: 17 apparently unrelated patients diagnosed with Coproporphyria, of which 15 had reported heterozygous variants in CPOX. 13 patients have experienced acute attacks (with or without skin lesions), 4 patients have had no attacks- diagnosis was established by measurement of fecal porphyrin. Missense variants are the most common.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005).
PMID: 11309681 Lamoril et al., 2001: 17 apparently unrelated patients diagnosed with Coproporphyria, of which 15 had reported heterozygous variants in CPOX. 13 patients have experienced acute attacks (with or without skin lesions), 4 patients have had no attacks- diagnosis was established by measurement of fecal porphyrin. Missense variants are the most common.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.

CPOX is associated with Coproporphyria 121300 (AR and AD) and Harderoporphyria 618892 (AR) in OMIM (accessed 14th Oct 2025).
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Comment on list classification: There at least 17 unrelated individuals with Coproporphyria harbouring monoallelic variants in CPOX, and at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance.
Based on the available evidence, CPOX should be rated Green for Rare anaemia.; to: Comment on list classification: There at least 17 unrelated individuals with Coproporphyria harbouring monoallelic variants in CPOX, and at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance. Based on the available evidence, CPOX should be rated Green for Rare anaemia.
Rare anaemia v3.10 CPOX Ida Ertmanska commented on gene: CPOX: Comment on list classification: There at least 17 unrelated individuals with Coproporphyria harbouring monoallelic variants in CPOX, and at least 5 unrelated families affected by Coproporphyria (AR) / Harderoporphyria (AR), with affected individuals harbouring biallelic variants in CPOX. Importantly, autosomal dominant Coproporphyria has low clinical penetrance.
Based on the available evidence, CPOX should be rated Green for Rare anaemia.
Rare anaemia v3.10 CPOX Ida Ertmanska changed review comment from: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005).
PMID: 11309681 Lamoril et al., 2001: 17 apparently unrelated patients diagnosed with Coproporphyria, of which 15 had reported heterozygous variants in CPOX. 13 patients have experienced acute attacks with or without skin lesions), 4 patients have had no attacks- diagnosis was established by measurement of fecal porphyrin. Missense variants are the most common.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.; to: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005).
PMID: 11309681 Lamoril et al., 2001: 17 apparently unrelated patients diagnosed with Coproporphyria, of which 15 had reported heterozygous variants in CPOX. 13 patients have experienced acute attacks (with or without skin lesions), 4 patients have had no attacks- diagnosis was established by measurement of fecal porphyrin. Missense variants are the most common.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.
Rare anaemia v3.10 CPOX Ida Ertmanska edited their review of gene: CPOX: Added comment: Coproporphyria (AD) is characterized by acute attacks of neurologic dysfunction. The attacks can be brought on by drugs, fasting, menstrual cycle, or infectious diseases. Disorder shows incomplete penetrance (PMID:16159891 Shmitt et al., 2005).
PMID: 11309681 Lamoril et al., 2001: 17 apparently unrelated patients diagnosed with Coproporphyria, of which 15 had reported heterozygous variants in CPOX. 13 patients have experienced acute attacks with or without skin lesions), 4 patients have had no attacks- diagnosis was established by measurement of fecal porphyrin. Missense variants are the most common.

Coproporphyria (AR) / Harderoporphyria (AR)
Harderoporphyria arises due to specific CPOX mutations that alter enzyme residues D400-K404; most patients described to date having at least one K404E allele.
As reviewed by Sharon Whatley, there are at least eight patients from five unrelated families with biallelic pathogenic CPOX variants, diagnosed with either Coproporphyria or Harderoporphyria (PMIDs: 9454777, 7757079, 21103937, 30828546, 40296768).

PMID: 21103937 Hasanoglu 2011
Male infant from a Turkish consanguineous family presented with the Harderoporphyria phenotype: neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. Heterozygous for c.980A>G (p.His327Arg) The patient died at 5 months old due to an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site.

PMID: 30828546 Moghe et al., 2019
A 78-year-old man with a history of neonatal anaemia and jaundice, and life-long photosensitivity; found to have harderoporphyria: increased porphyrins in urine, plasma, erythrocytes and feces, including large amounts of harderoporphyrin in feces and erythrocytes. CPOX variants: c.698A>G ( p.Asp233Gly) & c.1207_1218del12, p.Thr403_Gly406del.

PMID: 40296768 Kelestemur et al., 2025
2 siblings with harderoporphyria, homozygous for c.83_85del, p.S28* variant (WGS). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. Primary adrenal insufficiency.; Changed publications to: 7757079, 9454777, 11309681, 16159891, 21103937, 30828546, 38940544, 40296768
Rare anaemia v3.10 CPOX Ida Ertmanska gene: CPOX was added
gene: CPOX was added to Rare anaemia. Sources: Other
Mode of inheritance for gene: CPOX was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CPOX were set to 7757079; 9454777; 21103937; 30828546; 38940544; 40296768
Phenotypes for gene: CPOX were set to Coproporphyria, OMIM:121300; Harderoporphyria, OMIM:618892
Review for gene: CPOX was set to GREEN
Added comment: Review added on behalf of Sharon Whatley (International Porphyria Network):

Relevant metabolic investigation: Plasma porphyrin fluorescence emission and faecal coproporphyrin isomer (III:I) ratio (for hereditary coproporphyria) and faecal harderoporphyrin (for harderoporphyria)

PMID: 38940544 Aarsand reports that porphyrias are a group of rare inborn errors of metabolism caused by abnormal functioning of haem biosynthesis enzymes. Defects in the CPOX gene cause hereditary coproporphyria.

PMID: 16159891 Schmitt reports that there are two very rare, homozygous forms of HCP one of which is characterised by the faecal excretion of harderoporphyrin. Harderoporphyria has predominantly haematological manifestations such as neonatal jaundice, haemolytic anaemia and hepatosplenomegaly.

PMID: 30828546 Moghe, 9454777 Lamoril, 7757079 Lamoril, 40296768 Kelestemur, 21103937 Hasanoglu report eight patients (from five families) with biallelic pathogenic CPOX variants. They presented with neonatal jaundice, haemolytic anaemia and hepatosplenomegaly.

PMID: 16159891 Schmitt reports that during childhood and adulthood, a mild residual anaemia is chronically observed in harderoporphyria patients.

Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the CPOX gene, due to its low clinical penetrance (~0.4%).
Sources: Other
Rare anaemia v3.10 PPOX Sharon Whatley gene: PPOX was added
gene: PPOX was added to Rare anaemia. Sources: Other
Mode of inheritance for gene: PPOX was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PPOX were set to 38940544; 30828546; 9454777; 7757079; 40296768; 21103937
Phenotypes for gene: PPOX were set to 121300; 618892
Penetrance for gene: PPOX were set to Incomplete
Review for gene: PPOX was set to GREEN
Added comment: Relevant metabolic investigation: Plasma porphyrin fluorescence emission and faecal coproporphyrin isomer (III:I) ratio (for hereditary coproporphyria) and faecal harderoporphyrin (for harderoporphyria)

PMID: 38940544 Aarsand reports that porphyrias are a group of rare inborn errors of metabolism caused by abnormal functioning of haem biosynthesis enzymes. Defects in the CPOX gene cause hereditary coproporphyria.

PMID: 16159891 Schmitt reports that there are two very rare, homozygous forms of HCP one of which is characterised by the faecal excretion of harderoporphyrin. Harderoporphyria has predominantly haematological manifestations such as neonatal jaundice, haemolytic anaemia and hepatosplenomegaly.

PMID: 30828546 Moghe, 9454777 Lamoril, 7757079 Lamoril, 40296768 Kelestemur, 21103937 Hasanoglu report eight patients (from five families) with biallelic pathogenic CPOX variants. They presented with neonatal jaundice, haemolytic anaemia and hepatosplenomegaly.

PMID: 16159891 Schmitt reports that during childhood and adulthood, a mild residual anaemia is chronically observed in harderoporphyria patients.

Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the CPOX gene, due to its low clinical penetrance (~0.4%).
Sources: Other