title: Study of patients and carriers with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: difficulties in the diagnosis.
abstract: OBJECTIVE
  To search for biochemical and molecular markers for the diagnosis of patients and carriers with 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency.
  
  
  METHODS
  Organic acids in urine, MHBD activity in fibroblasts, immunoblotting and molecular studies were performed in seven patients. Seven carriers were also studied.
  
  
  RESULTS
  Under low protein diet or poor feeding all the patients showed only a slightly altered organic acid profile. Measurement of 2-methyl-3-hydroxybutyric acid and tiglylglycine after an isoleucine loading test, failed to demonstrate the carrier status of one patient. However, measurement of 2-ethylhydracrylic acid (EHA) was positive in all the carriers tested. MHBD activity was clearly deficient in males and in one female patient. We identified four missense mutations, two of them were novel.
  
  
  CONCLUSIONS
  Quantification of EHA may be of help for the diagnosis of the heterozygous condition. The carrier females showed the classical biochemical variability of X-linked diseases due to random X-chromosome inactivation.
authors.affiliation: Sección de Errores Congénitos del Metabolismo (IBC), Servicio de Bioquímica y Genética Molecular, and CIBER de Enfermedades Raras, Hospital Clínic, Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: García-Villoria
authors.forename: Aleix
authors.initials: A
authors.lastname: Navarro-Sastre
authors.forename: Carme
authors.initials: C
authors.lastname: Fons
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez-Cerdá
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldellou
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Fuentes-Castelló
authors.forename: Inmaculada
authors.initials: I
authors.lastname: González
authors.forename: Arturo
authors.initials: A
authors.lastname: Hernández-Gonzalez
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández
authors.forename: Jaume
authors.initials: J
authors.lastname: Campistol
authors.forename: Carina
authors.initials: C
authors.lastname: Delpiccolo
authors.forename: Nuria
authors.initials: N
authors.lastname: Cortés
authors.forename: Angel
authors.initials: A
authors.lastname: Messeguer
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases; D000429:Alcohol Oxidoreductases / Q000172:deficiency*; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006885:Hydroxybutyrates / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D014631:Valerates / Q000378:metabolism
chemical_list: D006885:Hydroxybutyrates; D014631:Valerates; C003603:tiglylglycine; C007674:2-ethylhydracrylic acid; C016579:2-methyl-3-hydroxybutyric acid; D000429:Alcohol Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C419903:2-methyl-3-hydroxybutyryl-coenzyme A dehydrogenase; D005998:Glycine