A case of methemoglobinemia type II due to NADH-cytochrome b5 reductase deficiency: Determination of the molecular basis

Recessive congenital methemoglobinemia type II: Hypoplastic basal ganglia in two siblings with a novel mutation of the cytochrome b5 reductase gene

“…4 Although hypoplasia of the basal ganglia would correlate with the dystonia and abnormal movements seen in RCM type II patients, there is only one reported case in the literature. 2 Our patients had bilateral symmetrical basal ganglia hypoplasia, with associated hypomyelination in patient 2. Frontotemporal brain atrophy was also noted, similar to previously reported cases.…”

Recessive congenital methemoglobinemia type II: Hypoplastic basal ganglia in two siblings with a novel mutation of the cytochrome b5 reductase gene

“…4 Although hypoplasia of the basal ganglia would correlate with the dystonia and abnormal movements seen in RCM type II patients, there is only one reported case in the literature. 2 Our patients had bilateral symmetrical basal ganglia hypoplasia, with associated hypomyelination in patient 2. Frontotemporal brain atrophy was also noted, similar to previously reported cases.…”

Congenital methemoglobinemia type II in a 5‐year‐old boy

“…Although these patients have many common clinical features, it seems that the proband that we report has a more severe phenotype than the patient reported by Aalfs et al in 2000. We propose that the novel deletion in combination with the p.R160X pathogenic variant in our proband may have contributed to this increased severity compared to the patient, who had two missense mutations. Deletions, splice site, and terminations appear to create the most severe methemoglobinemia phenotypes leading to type II rather than type I because of the significantly reduced methemoglobin reductase activity.…”

Compound heterozygosity of two missense mutations in the NADH‐cytochrome b5 reductase gene of a Polish patient with type I recessive congenital methaemoglobinaemia

“…The mutations have been found in all exons but in exon 1 and 1s. Type II is more often associated with stop codons or deletions, whereas type I is more likely caused by missense mutations leading to amino acid substitutions (19). Using the model of human b5R build on the basis of porcine b5R crystal structure it has been deduced (5) that b5R mutations causing methaemoglobinaemia type I are mainly localised in the surface of the protein leading to enzyme instability while mutations affecting active centre result in type II of the disease.…”

Recessive congenital methemoglobinemia type II: Hypoplastic basal ganglia in two siblings with a novel mutation of the cytochrome b5 reductase gene

“…4 Although hypoplasia of the basal ganglia would correlate with the dystonia and abnormal movements seen in RCM type II patients, there is only one reported case in the literature. 2 Our patients had bilateral symmetrical basal ganglia hypoplasia, with associated hypomyelination in patient 2. Frontotemporal brain atrophy was also noted, similar to previously reported cases.…”

Congenital methemoglobinemia type II in a 5‐year‐old boy

“…Although these patients have many common clinical features, it seems that the proband that we report has a more severe phenotype than the patient reported by Aalfs et al in 2000. We propose that the novel deletion in combination with the p.R160X pathogenic variant in our proband may have contributed to this increased severity compared to the patient, who had two missense mutations. Deletions, splice site, and terminations appear to create the most severe methemoglobinemia phenotypes leading to type II rather than type I because of the significantly reduced methemoglobin reductase activity.…”

Compound heterozygosity of two missense mutations in the NADH‐cytochrome b5 reductase gene of a Polish patient with type I recessive congenital methaemoglobinaemia

“…The mutations have been found in all exons but in exon 1 and 1s. Type II is more often associated with stop codons or deletions, whereas type I is more likely caused by missense mutations leading to amino acid substitutions (19). Using the model of human b5R build on the basis of porcine b5R crystal structure it has been deduced (5) that b5R mutations causing methaemoglobinaemia type I are mainly localised in the surface of the protein leading to enzyme instability while mutations affecting active centre result in type II of the disease.…”

Recessive congenital methemoglobinemia type II: Hypoplastic basal ganglia in two siblings with a novel mutation of the cytochrome b5 reductase gene

“…4 Although hypoplasia of the basal ganglia would correlate with the dystonia and abnormal movements seen in RCM type II patients, there is only one reported case in the literature. 2 Our patients had bilateral symmetrical basal ganglia hypoplasia, with associated hypomyelination in patient 2. Frontotemporal brain atrophy was also noted, similar to previously reported cases.…”

Congenital methemoglobinemia type II in a 5‐year‐old boy

“…Although these patients have many common clinical features, it seems that the proband that we report has a more severe phenotype than the patient reported by Aalfs et al in 2000. We propose that the novel deletion in combination with the p.R160X pathogenic variant in our proband may have contributed to this increased severity compared to the patient, who had two missense mutations. Deletions, splice site, and terminations appear to create the most severe methemoglobinemia phenotypes leading to type II rather than type I because of the significantly reduced methemoglobin reductase activity.…”

Compound heterozygosity of two missense mutations in the NADH‐cytochrome b5 reductase gene of a Polish patient with type I recessive congenital methaemoglobinaemia

“…The mutations have been found in all exons but in exon 1 and 1s. Type II is more often associated with stop codons or deletions, whereas type I is more likely caused by missense mutations leading to amino acid substitutions (19). Using the model of human b5R build on the basis of porcine b5R crystal structure it has been deduced (5) that b5R mutations causing methaemoglobinaemia type I are mainly localised in the surface of the protein leading to enzyme instability while mutations affecting active centre result in type II of the disease.…”