Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry.
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.
Matern
Dietrich
D
Department of Laboratory Medicine & Pathology, Mayo Clinic & Foundation, Rochester, Minnesota 55905, USA. matern@mayo.edu
He
Miao
M
Berry
Susan A
SA
Rinaldo
Piero
P
Whitley
Chester B
CB
Madsen
Pia P
PP
van Calcar
Sandra C
SC
Lussky
Richard C
RC
Andresen
Brage S
BS
Wolff
Jon A
JA
Vockley
Jerry
J
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
C116917:acylcarnitine; D007532:Isoleucine; C027333:3-methylbutyrylcarnitine; D044925:Oxidoreductases Acting on CH-CH Group Donors; C038808:2-methylacyl-CoA dehydrogenase; D002331:Carnitine