Neonatal-onset hereditary coproporphyria with male pseudohermaphrodism

Abstract

The appearance of hereditary coproporphyria (HCP) before puberty is very rare, and all reported cases of early-onset HCP have been in the homozygous or the compound heterozygous state. Some have been identified as harderoporphyria, which is a rare erythropoietic variant form of HCP. These conditions can be differentiated by molecular analysis because the gene abnormality responsible for harderoporphyria seems to be unique (K404E IntroductionHereditary coproporphyria (HCP) is a hereditary autosomaldominant disease of heme biosynthesis resulting from a partial deficiency of coproporphyrinogen oxidase (CPO). It is clinically characterized by neurologic dysfunction attacks and occasional photosensitivity. 1 HCP is rare before puberty, 2 and all reported early-onset cases have been in the homozygous 3-8 or the compound heterozygous state. 9 Harderoporphyria, a rare erythropoietic variant form of HCP, is characterized by neonatal hyperbilirubinemia and hemolytic anemia, hepatosplenomegaly, and sometimes photosensitivity. 6-9 To date, 3 families with harderoporphyria have been reported. Molecular analysis indicates that a CPO gene abnormality, K404E, was unique for the disease. 9 Therefore, HCP can be differentially diagnosed from harderoporphyria by both clinical and laboratory examinations and molecular analysis. Here, we describe a first case of neonatal-onset HCP in the heterozygous state with male pseudohermaphrodism. Study design Patient historyThe patient was born at term to healthy, nonconsanguineous Japanese parents with no family history of porphyria. Perinatal history was normal. The amniotic fluid and placenta were yellow, as occurred in a patient with congenital erythropoietic porphyria (CEP). 10 Shortly after birth, the infant was admitted to our hospital for tachypnea and severe jaundice. He displayed icteric skin, petechiae, hypotonia, lethargy, and marked hepatosplenomegaly. Laboratory data showed hypoglycemia (22 mg/dL blood sugar), thrombocytopenia (93 000/L platelets), and anemia (9.4 g/dL erythrocytes) with marked erythroblastosis (26 900/L erythroblasts), similar to what was seen in a patient with CEP. 11 Erythrocyte morphology showed some dacryocytes, leptocytes, and echinocytes. Based on these findings, his anemia was concluded to be hemolytic. Total serum bilirubin level was 14.16 mg/dL (indirect, 6.64 mg/dL). Respiratory distress and hypotonia were improved after intravenous glucose loading for hypoglycemia. Phototherapy was performed for hyperbilirubinemia to avert kernicterus on days 1 and 2. Soon afterward, the patient showed partial edema with vesicles and bulla. After his incubator was wrapped with UV cut-off film, no new skin lesions appeared. The severe hemolytic state, erythroblastosis, and morphologic abnormalities of erythrocyte disappeared, and partial regression of hepatosplenomegaly was observed in a few weeks. In the first week after birth, dark-brown urine was observed. Porphyrins were detected using reverse-phase high-performance liquid-chromatography. 12 He also had ambiguous...

Neonatal-Onset Hereditary Coproporphyria: A New Variant of Hereditary Coproporphyria

“…These results are consistent with HCP, but not harderoporphyria. Similar to our patient, another neonatal patient with HCP showed neonatal jaundice and hemolytic anemia with a (Table 3) (Takeuchi et al 2001). This case also did not have a mutation that is found in patients with harderoporphyria and the coproporphyrin III level in the feces was greatly increased.…”

“…Hypospadias and adrenocortical insufficiency were observed in our patient and in the previously reported neonatal patient with HCP (Table 3) (Takeuchi et al 2001). In patients with harderoporphyria and compound heterozygous mutations of p.Lys404Glu and IVS6 + 3A>G (Lamoril et al 1998), which result in exon 6 skipping at the mRNA level, only hypospadias was observed.…”

“…Based on these clinical and biological results, we concluded that our patient was an atypical case of HCP, who showed symptoms of erythropoietic porphyria from the neonatal period, as in a previous case (Takeuchi et al 2001), thus our case is only the second reported case of neonatal-onset HCP twice. We consider that neonatal-onset HCP is a variant of HCP.…”

“…HCP hereditary coproporphyria, CPOX coproporphyrinogen oxidase, COPRO coproporphyrin, HARDERO harderoporphyrin, homo homozygous mutation, hetero heterozygous mutation, ND not determined a Elder et al (1976) b Nordmann et al (1977) c d e Martasek et al (1994) f Kuhnel et al (2000) g Nordmann et al (1983) h Schmitt et al (2005) i Lamoril et al (1998) j Takeuchi et al (2001) …”