title: Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr).
abstract: Aldolase (E.C. 4.1.2.13), a homotetrameric protein encoded by the ALDOA gene, converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Three isozymes are encoded by distinct genes. The sole aldolase present in red blood cells and skeletal muscle is the A isozyme. We report here the case of a girl of Sicilian descent with aldolase A deficiency. Clinical manifestations included transfusion-dependent anemia until splenectomy at age 3 and increasing muscle weakness, with death at age 4 associated with rhabdomyolysis and hyperkalemia. Sequence analysis of the ALDOA coding regions revealed 2 novel heterozygous ALDOA mutations in conserved regions of the protein. The paternal allele encoded a nonsense mutation, Arg303X, in the enzyme-active site. The maternal allele encoded a missense mutation, Cys338Tyr, predicted to cause enzyme instability. This is the most severely affected patient reported to date and only the second with both rhabdomyolysis and hemolysis.
authors: Division of Genetics, Department of Neurology, Children's Hospital Boston, Dana Farber Cancer Institute and Harvard Medical School, MA 02115, USA.
authors: David C
authors: DC
authors: Yao
authors: Dean R
authors: DR
authors: Tolan
authors: Michael F
authors: MF
authors: Murray
authors: David J
authors: DJ
authors: Harris
authors: Basil T
authors: BT
authors: Darras
authors: Alon
authors: A
authors: Geva
authors: Ellis J
authors: EJ
authors: Neufeld
mesh_terms: D000595:Amino Acid Sequence; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics*; D002675:Child, Preschool; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology; D012206:Rhabdomyolysis / Q000235:genetics*
chemical_list: D005634:Fructose-Bisphosphate Aldolase