Abstract
Hereditary coproporphyria (HCP) is an autosomal dominant acute hepatic porphyria due to the half-normal activity of the heme biosynthetic enzyme, coproporphyrinogen oxidase (CPOX). The enzyme catalyzes the step-wise oxidative decarboxylation of the heme precursor, coproporphyrinogen III, to protoporphyrinogen IX via a tricarboxylic intermediate, harderoporphyrinogen. In autosomal dominant HCP, the deficient enzymatic activity results primarily in the accumulation of coproporphyrin III. To date, only a few homozygous HCP patients have been described, most having Harderoporphyria, a rare variant due to specific CPOX mutations that alter enzyme residues D400–K404, most patients described to date having at least one K404E allele. Here, we describe a Turkish male infant, the product of a consanguineous union, who presented with the Harderoporphyria phenotype including neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. He was homoallelic for the CPOX missense mutation, c.980A>G (p.H327R), and had massively increased urinary uroporphyrins I and III (9,250 and 2,910 μM, respectively) and coproporphyrins I and III (895 and 19,400 μM, respectively). The patient expired at 5 months of age from an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site, thereby accounting for the Harderoporphyria phenotype.
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This research was supported in part by grants from the National Institutes of Health (NIH) including a research grant (5 R01 DK026824) and a grant (1 U54 DK083909) for the Porphyria Consortium of the NIH Rare Diseases Clinical Research Network (RDCRN). Funding and /or programmatic support for this project has been provided by NIH Office of Rare Disease Clinical Research Network (ORDR). The views expressed in written materials or publications do not necessarily reflect the official policies of the Department of Health and Human Services.
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Communicated by: Georg Hoffmann
Competing interest: None declared.
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Hasanoglu, A., Balwani, M., Kasapkara, Ç.S. et al. Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R. J Inherit Metab Dis 34, 225–231 (2011). https://doi.org/10.1007/s10545-010-9237-9
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DOI: https://doi.org/10.1007/s10545-010-9237-9