title: [Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency in Argentina].
abstract: From the description of two pairs of siblings belonging to unrelated families, one Argentine family with a history of consanguinity and Irish ancestry and the other family native of Paraguay, in whom mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency, commonly known as beta-ketothiolase deficiency (beta-KTD, McKusick 203750; EC 2.3.1.9) was recognized. We tried to outline through this experience the clinical and biochemical consequences of this genetic defect in the 6th step of the isoleucine catabolism. The phenotyoic expression presented by the patients belonged to the classical form of beta-KTD. Seven to 15 months was the age at onset of the uniform clinical pattern this being essentially an association of one or several severe ketoacidotic episodes and hyperglycemia which was observed in two patients. The thin-layer chromatography of the tiglylglycine, and dinitrophenylhydrazone of the butanone were positive; aminoacidemia and aminoaciduria revealed normal levels. The organic acids having a unique profile obtained through gaschromatography and mass-spectrometry (GC/MS) showed excretion of large quantities of metabolites characteristic of the disease: 2-methyl-3-hydroxybutirate, 2-methylacetoacetic acid, tiglylglycine and 2-ethylhydracrilic acid which led us to establish the biochemical diagnosis of beta-KTD. The assay of the beta-ketothiolase in lymphocytes and polymorphonuclear leukocytes of the only surviving patient (VT) showed absence of activation by the K+ ion when the acetoacetyl-CoA was used as a substrate. This first Argentine report about beta-KTD leads us to mention three amplifying aspects with regards to previous literature: it adds other different ethnic ancestries of patients, points out a morphological analysis of autopsy material with unchanged structures in the brain, liver and kidneys and marks in the patient VT a dissociation between a symptom-free clinical pattern since age 7 and the persistent biochemical abnormality until the present age, 15 years. The knowledge of the existence of these diseases in our country together with the availability and access to GC/MS of high precision and speed, will allow early diagnosis and better therapeutic results.
authors.affiliation: Centro de Estudios de las Metabolopatías Congénitas, CEMECO, Hospital de Niños, Córdoba, Argentina.
authors.forename: R D
authors.initials: RD
authors.lastname: de Kremer
authors.forename: C D
authors.initials: CD
authors.lastname: de Boldini
authors.forename: R I
authors.initials: RI
authors.lastname: Kelley
authors.forename: G E
authors.initials: GE
authors.lastname: Civallero
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency*; D001118:Argentina; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis; D008928:Mitochondria / Q000201:enzymology*
chemical_list: D007657:Ketone Bodies; D007532:Isoleucine; D000102:Acetyl-CoA C-Acyltransferase