An italian case of red cell triosephosphate isomerase deficiency caused by mutation at codon104gag→gac (Gl104→Asp)

Triosephosphate isomerase (TPI) deficiency is a rare autosomal recessive disease (fewer than 35 cases reported), characterized by non spherocytic hemolytic anemia, severe and progressive neurological and muscular disorders and increased susceptibility to infections The gene, localized at 12pl3 chromosome, encodes for 247 amino acids, and is expressed in all tissues Seven different mutations have been so far reported (codons 41TGT+TAT 17()ATTGTT [Q4GAG+GAC 122°°+°. IgUCGA+TGA 231GTGAIG. 240Trc-K~Tc) The mutation 104 is the most frequent, having been found in 30/40 alkies from various countries (USA. UK. Greece. Bulgary. Turkey and Australia). We describe the first Italian case of TPI deficiency characterized at the molecular level. The clinical history and results of biochemical characterization have already been reported (Zanella et al. Scand J Haematol. 34:417.1985) The mutant enzyme showed normal K, for GAP and increased 1 for DHAP. decreased thermal stability and abnormal electrophorettc pattern. Since the patient was dead at the age of two vrs for respiratory failure, die study was performed on the parents. The genomic DNA was extracted from pheripheral blood and exon 3 amplified by Porymerase Chain Reaction using intronic primers (Schneider A et al. Am J Hcmatol 50:263.1999) to verify the presence of mutation 104. The PCR products were digested with restriction enzyme Dde I. Both parents carried the mutation at heterozygous level The clinical course of the disease and the enzyme biochemical abnormalities in our patient are similar to those of other cases homozygote for this mutation The finding of mutation 104 also in Italy confirms its worldwide spreading and may be useful for prenatal diagnosis.