title: Metabolic studies in twin brothers with 2-methylacetoacetyl-CoA thiolase deficiency.
abstract: We report clinical and biological investigations in two patients (twin brothers) with 2-methylacetoacetyl-CoA thiolase deficiency. Main clinical features included important staturo-ponderal delay, frequent infectious rhinopharyngitis episodes and an acute metabolic acidosis at the age of 4 years, this metabolic decompensation being adequately halted by bicarbonate supplementation. Since that age, patients developed rather favorably, however, with persistence of the staturo-ponderal delay. Organicaciduria typical of 2-methylacetoacetyl-CoA thiolase deficiency 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 concentrations and enhanced acyl/free carnitine ratios. Determination of acylcarnitine profiles showed that patients excreted excessive amounts of several acylcarnitines in urine including propionyl, butyryl, isobutyryl, isovaleryl, 2-methylbutyryl and tiglyl-carnitine, the latter acylcarnitine being prominent with, in one of the patients, occurrence of a previously undescribed isomer of this carnitine ester, possibly 2-ethylacrylyl-carnitine. Excretion of these acylcarnitines in urine was increased in response to L-carnitine although, as a whole, this therapy resulted in a less important stimulation of esterified carnitine removal in urine from patients than in the case of supplemented controls. Biochemical investigations on cultured skin fibroblasts confirmed 2-methylacetoacetyl-CoA thiolase deficiency. Through the present report on this rare disease in two siblings, we would like to underline that acylcarnitines can be used in the diagnosis of 2-methylacetoacetyl-CoA thiolase deficiency, a view supported by acylcarnitine profiles further determined in another patient with proven oxothiolase deficiency, adding this pathology to the list of beta-oxidation disorders that may be screened successfully through determination of acylcarnitine profiles in body fluids.
authors.affiliation: Laboratoire de Biochimie, Hôpital Huriez, Centre Hospitalo-Universitaire de Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Fontaine
authors.forename: G
authors.initials: G
authors.lastname: Briand
authors.forename: N
authors.initials: N
authors.lastname: Ser
authors.forename: I
authors.initials: I
authors.lastname: Armelin
authors.forename: M O
authors.initials: MO
authors.lastname: Rolland
authors.forename: P
authors.initials: P
authors.lastname: Degand
authors.forename: J
authors.initials: J
authors.lastname: Vamecq
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency*; D000138:Acidosis / Q000378:metabolism* / Q000628:therapy / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine*; D002478:Cells, Cultured; D002675:Child, Preschool; D004200:Diseases in Twins; D005227:Fatty Acids / Q000378:metabolism; D006128:Growth; D006801:Humans; D010084:Oxidation-Reduction; D012867:Skin / Q000201:enzymology*
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; C104275:tiglylcarnitine; D000102:Acetyl-CoA C-Acyltransferase; D002331:Carnitine