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We report the first case of a child with recessive hereditary methemoglobinemia type II with demonstrated cerebellar atrophy. This very rare blood disorder results in mild cyanosis, profound mental and motor impairment, and movement disorders in infancy and childhood. We suggest that children with unexplained severe encephalopathy and cerebellar atrophy should also be tested for hereditary methemoglobinemia type II.

We report the hematological, biochemical, and molecular characteristics of a new defective adenylate kinase (AK) variant associated with chronic hemolytic anemia. The propositus was a 3-year-old girl of southern Italian origin with a history of severe anemia and occasional need for blood transfusion. The study of the most important red cell enzymes revealed low AK activity (22% of normal) in the propositus and intermediate values in the parents. The sequence of erythrocyte AK-1 gene showed a new homozygous mutation (delG138) determining a frameshift and a premature stop at codon 91.

ABSTRACT We evaluated the iron status and searched for mutations C282Y and H63D in the hereditary hemochromatosis gene ( HFE ) in 34 pyruvate kinase (PK)-deficient patients from 29 unrelated families. Nine had received multiple transfusions. Thirteen of the 25 nontransfused patients displayed increased serum ferritin concentration, in the absence of conditions known to raise this parameter. HFE genotype was abnormal in 9 of 34 patients. The allele frequency was 1.8% for mutation 845G→ (C282Y) and 16.1% for mutation 187C→:G (H63D). Nontransfused subjects with abnormal genotype had serum ferritin and transferrin saturation values significantly higher than those with wild-type genotype. Of the 12 adult nontransfused patients with increased iron status parameters, 1 was C282Y homozygous, 1 compound heterozygous for C282Y and H63D, 3 H63D heterozygous, and 7 had a normal HFE genotype. Serum ferritin and transferrin saturation were not related to hemoglobin, reticulocytes, and bilirubin concentration. At multivariate analysis serum ferritin was independently associated with age and gender, but not with splenectomy and HFE genotypes. The retrospective evaluation of the iron status profile of 10 patients (3 with abnormal and 7 with wild-type HFE genotype) with at least 10 years follow-up showed that overt iron accumulation requiring iron chelation had occurred only in the 3 patients (2 of whom were splenectomized) with the mutated HFE gene.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder characterized by an acquired PIG-A gene mutation. The clinical symptoms are intravascular hemolysis and hemoglobinuria. A variety of mutations in PIG-A gene have been so far reported. The aim of the study was to investigate the molecular defect in 8 patients with hemolytic PNH and in a 51 years old female who spontaneously recovered from severe hemolytic PNH (SL). The study of the entire codifying region and flanking intronic sequences of PIG-A gene was done by SSCP analysis and sequencing. 8 new and one known mutations were detected. Results are reported in the table. Mutation C55T has been already described in 5 PNH patients, but its nature was controversial. C55T was the only mutation found in patient SL. It was also detected in patient DTI, in association with T728C. To exclude the somatic origin of this variant, the mucous membrane cells were analyzed and found to be positive. C55T was also present in 1/100 normal alleles investigated, thus confirming its polymorphic nature. Mutations so far identified could be useful as molecular markers for monitoring the course of the disease during therapy.