title: Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry.
abstract: OBJECTIVE
  2-methylbutyryl-CoA dehydrogenase deficiency, also known as short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency, is a recently described autosomal recessive disorder of L-isoleucine metabolism. Only 4 affected individuals in 2 families have been described. One patient developed athetoid cerebral palsy, and another had severe motor developmental delay with muscle atrophy. A sibling of the first patient is asymptomatic after prenatal diagnosis and early treatment. Family investigations in the second family revealed that the patient's mother was also affected but asymptomatic.
  
  
  METHODS
  We report 8 additional patients identified by prospective newborn screening using tandem mass spectrometry.
  
  
  RESULTS
  Molecular genetic analysis performed for 3 of these patients revealed that all are homozygous for an 1165A>G mutation that causes skipping of exon 10 of the SBCAD gene. Although there was no obvious consanguinity, all patients belong to the Hmong, an ancient ethnic group that originated in China and constitutes only 0.8% and 0.6% of the Minnesota and Wisconsin population, respectively. Dietary treatment was initiated in the neonatal period. Except for 1 patient who developed mild muscle hypotonia, all patients remain asymptomatic at ages ranging from 3 to 14 months of age.
  
  
  CONCLUSIONS
  These cases suggest that SBCAD deficiency is another inborn error of metabolism detectable by newborn screening using tandem mass spectrometry. The continued efficacy of long-term dietary therapy instituted presymptomatically remains to be established.
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic & Foundation, Rochester, Minnesota 55905, USA. matern@mayo.edu
authors.forename: Dietrich
authors.initials: D
authors.lastname: Matern
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Susan A
authors.initials: SA
authors.lastname: Berry
authors.forename: Piero
authors.initials: P
authors.lastname: Rinaldo
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
authors.forename: Pia P
authors.initials: PP
authors.lastname: Madsen
authors.forename: Sandra C
authors.initials: SC
authors.lastname: van Calcar
authors.forename: Richard C
authors.initials: RC
authors.lastname: Lussky
authors.forename: Brage S
authors.initials: BS
authors.lastname: Andresen
authors.forename: Jon A
authors.initials: JA
authors.lastname: Wolff
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000178:diet therapy / Q000201:enzymology / Q000208:ethnology / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D018753:Diet, Protein-Restricted; D005006:Ethnicity / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics / Q000517:prevention & control; D007532:Isoleucine / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D015997:Neonatal Screening / Q000379:methods; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency* / Q000235:genetics; D017384:Sequence Deletion; D016896:Treatment Outcome
chemical_list: C116917:acylcarnitine; D007532:Isoleucine; C027333:3-methylbutyrylcarnitine; D044925:Oxidoreductases Acting on CH-CH Group Donors; C038808:2-methylacyl-CoA dehydrogenase; D002331:Carnitine