METABOLIC STUDIES IN TWIN BROTHERS WITH 2-METHYLACETOACETYL-COA THIOLASE DEFICIENCY

We report clinical and biological investigations in two patients (twin brothers) with 2-methylacetoacetyl-CoA thiolase deficiency. Main clin ical features included important stature-ponderal delay, frequent infe ctious rhinopharyngitis episodes and an acute metabolic acidosis at th e age of 4 years, this metabolic decompensation being adequately halte d by bicarbonate supplementation. Since that age, patients developed r ather favorably, however, with persistence of the stature-ponderal del ay. Organicaciduria typical of 2-methylacetoacetyl-CoA thiolase defici ency was recorded consisting of excessive excretion of tiglylglycine, 2-methyl-3-hydroxybutyrate, 3-hydroxyisovalerate, 2-methylglutaconate, adipate and 2-methylacetoacetate. Blood carnitine levels were altered in patients with increased total and esterified carnitine concentrati ons and enhanced acyl/free carnitine ratios. Determination of acylcarn itine profiles showed that patients excreted excessive amounts of seve ral acylcarnitines in urine including propionyl, butyryl, isobutyryl, isovaleryl, 2-methylbutyryl and tiglyl-carnitine, the latter acylcarni tine being prominent with, in one of the patients, occurrence of a pre viously undescribed isomer of this carnitine ester, possibly 2-ethylac rylylcarnitine. Excretion of these acylcarnitines in urine was increas ed in response to L-carnitine although, as a whole, this therapy resul ted in a less important stimulation of esterified carnitine removal in urine from patients than in the case of supplemented controls. Bioche mical investigations on cultured skin fibroblasts confirmed 2-methylac etoacetyl-CoA thiolase deficiency. Through the present report on this rare disease in two siblings, we would like to underline that acylcarn itines can be used in the diagnosis of 2-methylacetoacetyl-CoA thiolas e deficiency, a view supported by acylcarnitine profiles further deter mined in another patient with proven oxothiolase deficiency, adding th is pathology to the list of beta-oxidation disorders that may be scree ned successfully through determination of acylcarnitine profiles in bo dy fluids.