Hegesh et al. (1986) described the highly instructive case of a female Yemenite Jewish baby who turned blue at 7 days of age and was persistently cyanotic for her 26 years to the time of report. There were ... Hegesh et al. (1986) described the highly instructive case of a female Yemenite Jewish baby who turned blue at 7 days of age and was persistently cyanotic for her 26 years to the time of report. There were no neurologic symptoms. Giordano et al. (1994) reported in full on the findings in this patient, who was said to be the only example of type IV methemoglobinemia described. Hegesh et al. (1986) had reported that the parents and 6 sibs had normal methemoglobin levels, whereas those in the patient varied between 12% and 19%. The patient's erythrocyte cytochrome b5 levels were about 25% of those found in other family members. Polyacrylamide gel electrophoresis of cytochrome b5 from the patient and family members demonstrated no differences in mobility. The patient exhibited female genitalia at birth but was subsequently determined to be a male pseudohermaphrodite. Giordano et al. (1994) suggested that the pseudohermaphroditism was also caused by the cytochrome b5 defect. Androgen deficiencies due to defects in 17-alpha-hydroxylase activity are a known cause of pseudohermaphroditism in males (202110), and cytochrome b5 has been shown to participate in 17-alpha hydroxylation in adrenal steroidogenesis by serving as an electron donor.
In a patient with type IV hereditary methemoglobinemia originally reported by Hegesh et al. (1986), Steggles et al. (1992) identified a homozygous splice site mutation in the CYB5A gene (613218.0001), resulting in premature termination of the protein. ... In a patient with type IV hereditary methemoglobinemia originally reported by Hegesh et al. (1986), Steggles et al. (1992) identified a homozygous splice site mutation in the CYB5A gene (613218.0001), resulting in premature termination of the protein. Steggles et al. (1992) indicated that whereas more than 300 patients had been reported with hereditary methemoglobinemia types I or II (250800), only 1 case of type IV had been reported. The rarity may be due to lethality of most type IV mutations.