title: [Phenotypic expression variation of isovaleric acidemia in Argentinian patients. A long term follow-up].
abstract: In this paper we discuss the first five Argentinean patients presenting isovaleric acidemia (IVA), an alteration of leucine catabolism due to a genetic defect of isovaleryl-CoA dehydrogenase. Belonging to unrelated families, one from native (H. Fam.) and the other from Italian ancestry (M. Fam.); the patients presented the clinical pattern highly suggestive of the disease: they were siblings, had disease-free intervals, vomiting, ketoacidosis crises, "sweaty feet" odor and progression of the neurologic involvement from somnolence and stupor to profound coma. In the four children of H. Fam. the disease had a late but severe beginning; one of the girls died (N.H.). The boy from M. Fam. presented a neonatal form of clearly benign course. The disease was confirmed by gas-chromatography (GC) of volatile acids in serum and also by the typical urinary acid GC-profiles (Fig. 1, A and B); the isovalerylglycine quantitative evaluation in urinary samples collected during crises is shown in Table 1. The morphological findings in liver and brain of N.H. showed at the ultrastructural study, an extensive fatty degeneration and greatly marked mitochondrial alterations in the liver and edema, neuronal karyorrhexis and karyolysis in the brain (Fig. 2). The therapeutic protocol based on a low leucine or low protein diet and use of glycine is described. The evolutionary follow up, more than 10 years for the first case, showed a normal mental development in three of them and retardation in the first child of H. Fam., who had a late diagnosis. IVA is still valuable as a paradigm in the acquisition of a highly clinical suspicion and for its introduction in the study of genetic organic acidemias.
authors.affiliation: Centro de Estudio de las Metabolopatías Congénitas, CEMECO, Facultad de Ciencias Médicas, Hospital de Niños de Córdoba, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Dodelson de Kremer
authors.forename: C
authors.initials: C
authors.lastname: Depetris de Boldini
authors.forename: A
authors.initials: A
authors.lastname: Paschini de Capra
authors.forename: E
authors.initials: E
authors.lastname: Hliba
authors.forename: L
authors.initials: L
authors.lastname: Corbella
mesh_terms: D000138:Acidosis / Q000235:genetics*; D001921:Brain / Q000648:ultrastructure; D002675:Child, Preschool; D002855:Chromatography, Thin Layer; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D005998:Glycine / Q000031:analogs & derivatives*; D045782:Hemiterpenes; D006801:Humans; D007223:Infant; D050769:Isovaleryl-CoA Dehydrogenase; D008099:Liver / Q000648:ultrastructure; D008297:Male; D010088:Oxidoreductases / Q000172:deficiency*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010421:Pentanoic Acids / Q000097:blood*; D010641:Phenotype
chemical_list: D045782:Hemiterpenes; D010421:Pentanoic Acids; C008216:isovaleric acid; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050769:Isovaleryl-CoA Dehydrogenase; D005998:Glycine
vernacular_title: Variación en la expresión fenotípica de la acidemia isovalérica en pacientes argentinos. Observaciones de un prolongado seguimiento.