Organic Acid Disorders

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Disease Name 2-methylbutyryl-CoA dehydrogenase deficiency
Alternate name(s) Short/branched chain acyl-CoA dehydrogenase deficiency,
Acronym N/A
Disease Classification Organic Acid Disorder
Variants None
Variant name N/A
Symptom onset Variable
Symptoms One patient presented with neonatal onset of hypotonia, lethargy, apnea and hypoglycemia. At four years of age, he has developmental delay, choreoathetoid cerebral palsy and visual deficits. Another patient presented in the second year of life with motor delay, muscular atrophy and strabismus. A sibling identified prenatally and 8 Hmong patients identified by newborn screening remain asymptomatic on treatment. At least 4 asymptomatic relatives of these patients have been described with gene mutations and/or elevated excretion of 2-methylbutyrylglycine.
Natural history without treatment Ranges from asymptomatic to acute neonatal decomposition with neurological deficits. The limited number of patients makes it difficult to determine the natural history of the disorder. However, the disorder is not thought to be benign in that asymptomatic individuals may not have been exposed to the environmental stressors (i.e. fasting) that can cause symptoms.
Natural history with treatment ITreatment in a symptomatic patient resolved episodic hypoglycemia but the neurologic dysfunction remains. Other patients treated from birth are asymptomatic thus far but the efficacy of the treatment remains to be established.
Treatment Protein restriction, carnitine supplementation, avoidance of fasting.
Other N/A
Physical phenotype None reported
Inheritance Autosomal recessive
General population incidence Rare; < than 20 patients identified
Ethnic differences Yes
Population Hmong
Ethnic incidence As high as 1/500
Enzyme location Mitochondria
Enzyme Function Metabolism of L-isoleucine
Missing Enzyme 2-methylbutyryl-CoA dehydrogenase
Metabolite changes Increased 2-methylbutyryl, increased 2-methylbutyrylcarnitine.
Gene location 10q25-q26
DNA testing available Research
DNA testing detail A common mutation has been identified in the Hmong population – M356V which causes skipping of exon 10 in the SBCAD.
Prenatal testing Enzyme analysis in amniocytes or CVS
MS/MS Profile Elevated C5 isovaleryl-carnitine
Genetests Link
Support Group

Organic Acidemia Association

Save Babies through Screening Foundation

Genetic Alliance

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