Prospective diagnosis of 2-Methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry

Dietrich Matern, Miao He, Susan A. Berry, Piero Rinaldo, Chester B. Whitley, Pia P. Madsen, Sandra C. Van Calcar, Richard C. Lussky, Brage S. Andresen, Jon A. Wolff, Jerry Vockley

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)74-78
Number of pages5
JournalPediatrics
Volume112
Issue number1 I
DOIs
StatePublished - Jul 1 2003

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Tandem Mass Spectrometry
Newborn Infant
Population
Butyryl-CoA Dehydrogenase
Consanguinity
Inborn Errors Metabolism
Muscle Hypotonia
Muscular Atrophy
2-Methylbutyryl-CoA Dehydrogenase Deficiency
Isoleucine
Cerebral Palsy
Prenatal Diagnosis
Ethnic Groups
Siblings
Molecular Biology
Exons
China
Therapeutics
Mothers
Mutation

Keywords

  • 2-Methylbutyryl-CoA dehydrogenase deficiency
  • ACADSB
  • Founder effect
  • Hmong
  • L-isoleucine
  • Newborn screening
  • SBCAD
  • Short/branched-chain acyl-CoA dehydrogenase deficiency
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Prospective diagnosis of 2-Methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry. / Matern, Dietrich; He, Miao; Berry, Susan A.; Rinaldo, Piero; Whitley, Chester B.; Madsen, Pia P.; Van Calcar, Sandra C.; Lussky, Richard C.; Andresen, Brage S.; Wolff, Jon A.; Vockley, Jerry.

In: Pediatrics, Vol. 112, No. 1 I, 01.07.2003, p. 74-78.

Research output: Contribution to journalArticle

Matern, D, He, M, Berry, SA, Rinaldo, P, Whitley, CB, Madsen, PP, Van Calcar, SC, Lussky, RC, Andresen, BS, Wolff, JA & Vockley, J 2003, 'Prospective diagnosis of 2-Methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry', Pediatrics, vol. 112, no. 1 I, pp. 74-78. https://doi.org/10.1542/peds.112.1.74
Matern, Dietrich ; He, Miao ; Berry, Susan A. ; Rinaldo, Piero ; Whitley, Chester B. ; Madsen, Pia P. ; Van Calcar, Sandra C. ; Lussky, Richard C. ; Andresen, Brage S. ; Wolff, Jon A. ; Vockley, Jerry. / Prospective diagnosis of 2-Methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry. In: Pediatrics. 2003 ; Vol. 112, No. 1 I. pp. 74-78.
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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.",
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AU - Matern, Dietrich

AU - He, Miao

AU - Berry, Susan A.

AU - Rinaldo, Piero

AU - Whitley, Chester B.

AU - Madsen, Pia P.

AU - Van Calcar, Sandra C.

AU - Lussky, Richard C.

AU - Andresen, Brage S.

AU - Wolff, Jon A.

AU - Vockley, Jerry

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

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KW - Short/branched-chain acyl-CoA dehydrogenase deficiency

KW - Tandem mass spectrometry

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