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PEDIATRICS Vol. 112 No. 1 July 2003, pp. 74-78

Prospective Diagnosis of 2-Methylbutyryl-CoA Dehydrogenase Deficiency in the Hmong Population by Newborn Screening Using Tandem Mass Spectrometry

Dietrich Matern, MD*,{ddagger}, Miao He, PhD{ddagger}, Susan A. Berry, MD§, Piero Rinaldo, MD, PhD*,{ddagger}, Chester B. Whitley, PhD, MD§, Pia P. Madsen||, Sandra C. van Calcar, MS, Richard C. Lussky, MD#, Brage S. Andresen, PhD||, Jon A. Wolff, MD and Jerry Vockley, MD, PhD{ddagger}

* Departments of Laboratory Medicine & Pathology
{ddagger} Medical Genetics, Mayo Clinic & Foundation, Rochester, Minnesota
§ Department of Pediatrics and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota
|| Research Unit for Molecular Medicine and Institute of Human Genetics, Aarhus University, Aarhus, Denmark
Waisman Center and Department of Pediatrics, University of Wisconsin, Madison, Wisconsin
# Hennepin County Medical Center, Minneapolis, Minnesota

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.

Key Words: 2-methylbutyryl-CoA dehydrogenase deficiency • short/branched-chain acyl-CoA dehydrogenase deficiency • SBCAD • ACADSB • L-isoleucine • newborn screening • tandem mass spectrometry • Hmong • founder effect

Abbreviations: SBCAD, short/branched-chain acyl-CoA dehydrogenase • MS/MS, tandem mass spectrometry

Received for publication Jul 2, 2002; Accepted Nov 12, 2002.




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