Organic Acid Disorders

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Disease Name Methylmalonic acidemia, Vitamin B-12 responsive
Alternate name(s) Methylmalonic acidemia, Vitamin B-12 responsive, due to defect in adenosylcobalamin, cblA complementation type; Methylmalonic acidemia, cblA type; Methylmalonic acidemia, Vitamin B-12 responsive, due to defect in synthesis of adenosylcobalamin, cbl B complementation type
Disease Classification Organic Acid Disorder
Variants Yes
Variant name Methylmalonic acidemia, Vitamin B-12 non-responsive; Combined deficiency of methylmalonyl-CoA mutase and homocysteine
Symptom onset Variable. Ranges from the first days of life to completely asymptomatic.
Symptoms Episodic ketoacidosis with vomiting accompanied by lethargy and coma which can lead to death. Survivors can have developmental delays, growth retardation, spastic quadriparesis, dystonia and seizures. Neutropenia, thrombocytopenia and osteoporosis are common complications.
Natural history without treatment Variable depending on the enzyme defect. Some will die in the newborn period, others will survive with deficits and others will be asymptomatic.
Natural history with treatment

CblA: Good prognosis with injections of hydroxy-cobalamin (OH-cbl) which reverses biochemical and clinical abnormalities in about 90% of patients.

CblB: Equal fractions of affected patients are alive and well, alive and impaired, or deceased. The age of onset of symptoms can help prognosticate outcome – those patients with a later onset of symptoms have a more benign course. Approximately 40% of patients will respond with a drop in MMA level when given OH-cbl injections.

Treatment Protein restricted diet, OH-cbl injections, carnitine supplementation, oral antibiotic therapy to decrease proprionate and medical foods. Liver transplant or combined liver/kidney transplant may increase metabolic control, but may not prevent neurologic complications.
Other N/A
Physical phenotype Minor facial dysmorphisms including high forehead, broad nasal bridge, epicanthal folds, long, smooth philtrum and triangular mouth. A variety of skin lesions can be seen in patients due to moniliasis.
Inheritance Autosomal recessive
General population incidence 1:48,000
Ethnic differences No known population at increased risk
Population N/A
Ethnic incidence N/A
Enzyme location Mitochondria
Enzyme Function Production of adenosylcobalamin
Missing Enzyme Cobalamin A (cblA) deficiency: cobalamin reductase
Cobalamin B (cblB) deficiency: cobalamin adenosyltransferase
Metabolite changes Elevated glycine in urine
Gene MMAA (cobalamin A disease)
MMAB (cobalamin B disease)
Gene location MMAA: 4q31.1-q31.2
MMAB: 12q24
DNA testing available Sequencing available internationally
DNA testing detail N/A
Prenatal testing Possible via enzyme assay on amniocytes or CVS..
MS/MS Profile Elevated C3 propionyl carnitine, elevated C4 DC methylmalonyl carnitine.
Genetests Link
Support Group

Organic Acidemia Association

Save Babies through Screening Foundation

Genetic Alliance

Fatty Oxidation Disorder (FOD) Family Support Group

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