2-Methylbutyryl-coenzyme a dehydrogenase deficiency: A new inborn error of L-isoleucine metabolism

K. Michael Gibson; Terry G. Burlingame; Boris Hogema; Cornelis Jakobs; Ruud B.H. Schutgens; David Millington; Charles R. Roe; Diane S. Roe; Lawrence Sweetman; Robert D. Steiner; Leesa Linck; Parhawa Pohowalla; Martine Sacks; Doreen Kiss; Piero Rinaldo; Jerry Vockley

doi:10.1203/00006450-200006000-00025

2-Methylbutyryl-coenzyme a dehydrogenase deficiency: A new inborn error of L-isoleucine metabolism

K. Michael Gibson, Terry G. Burlingame, Boris Hogema, Cornelis Jakobs, Ruud B.H. Schutgens, David Millington, Charles R. Roe, Diane S. Roe, Lawrence Sweetman, Robert D. Steiner, Leesa Linck, Parhawa Pohowalla, Martine Sacks, Doreen Kiss, Piero Rinaldo, Jerry Vockley

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Abstract

An 4-mo-old male was found to have an isolated increase in 2- methylbutyrylglycine (2-MBG) and 2-methylbutyrylcarnitine (2MBC) in physiologic fluids. In vitro oxidation studies in cultured fibroblasts using ¹³C- and ¹⁴C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in Escherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female ferns, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.

Original language	English (US)
Pages (from-to)	830-833
Number of pages	4
Journal	Pediatric Research
Volume	47
Issue number	6
DOIs	https://doi.org/10.1203/00006450-200006000-00025
State	Published - Jun 2000
Externally published	Yes

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health

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10.1203/00006450-200006000-00025

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Gibson, K. M., Burlingame, T. G., Hogema, B., Jakobs, C., Schutgens, R. B. H., Millington, D., Roe, C. R., Roe, D. S., Sweetman, L., Steiner, R. D., Linck, L., Pohowalla, P., Sacks, M., Kiss, D., Rinaldo, P., & Vockley, J. (2000). 2-Methylbutyryl-coenzyme a dehydrogenase deficiency: A new inborn error of L-isoleucine metabolism. Pediatric Research, 47(6), 830-833. https://doi.org/10.1203/00006450-200006000-00025

Gibson, KM, Burlingame, TG, Hogema, B, Jakobs, C, Schutgens, RBH, Millington, D, Roe, CR, Roe, DS, Sweetman, L, Steiner, RD, Linck, L, Pohowalla, P, Sacks, M, Kiss, D, Rinaldo, P & Vockley, J 2000, '2-Methylbutyryl-coenzyme a dehydrogenase deficiency: A new inborn error of L-isoleucine metabolism', Pediatric Research, vol. 47, no. 6, pp. 830-833. https://doi.org/10.1203/00006450-200006000-00025

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title = "2-Methylbutyryl-coenzyme a dehydrogenase deficiency: A new inborn error of L-isoleucine metabolism",

abstract = "An 4-mo-old male was found to have an isolated increase in 2- methylbutyrylglycine (2-MBG) and 2-methylbutyrylcarnitine (2MBC) in physiologic fluids. In vitro oxidation studies in cultured fibroblasts using 13C- and 14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in Escherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female ferns, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.",

author = "Gibson, {K. Michael} and Burlingame, {Terry G.} and Boris Hogema and Cornelis Jakobs and Schutgens, {Ruud B.H.} and David Millington and Roe, {Charles R.} and Roe, {Diane S.} and Lawrence Sweetman and Steiner, {Robert D.} and Leesa Linck and Parhawa Pohowalla and Martine Sacks and Doreen Kiss and Piero Rinaldo and Jerry Vockley",

year = "2000",

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doi = "10.1203/00006450-200006000-00025",

language = "English (US)",

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AU - Burlingame, Terry G.

AU - Hogema, Boris

AU - Jakobs, Cornelis

AU - Schutgens, Ruud B.H.

AU - Millington, David

AU - Roe, Charles R.

AU - Roe, Diane S.

AU - Sweetman, Lawrence

AU - Steiner, Robert D.

AU - Linck, Leesa

AU - Pohowalla, Parhawa

AU - Sacks, Martine

AU - Kiss, Doreen

AU - Rinaldo, Piero

AU - Vockley, Jerry

PY - 2000/6

Y1 - 2000/6

N2 - An 4-mo-old male was found to have an isolated increase in 2- methylbutyrylglycine (2-MBG) and 2-methylbutyrylcarnitine (2MBC) in physiologic fluids. In vitro oxidation studies in cultured fibroblasts using 13C- and 14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in Escherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female ferns, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.

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2-Methylbutyryl-coenzyme a dehydrogenase deficiency: A new inborn error of L-isoleucine metabolism

Abstract

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