||Methylmalonic acidemia, Vitamin B-12 non-responsive
|| Methylmalonic aciduria due to methylmalonic CoA mutase deficiency,
Complementation group mut0, Methylmalonyl-CoA mutase
||Organic Acid Disorder
||Vitamin B12 metabolic defect with methylmalonic acidemia and homocystinuria
||Eighty percent of infants become ill during the first week or life
and 90% will present by the end of the first month. Infants with the
less severe mut- may present later than the first month.
A few may remain asymptomatic or present much later in life depending
on the residual enzyme activity and the metabolic stressors.
||Most common signs and symptoms are lethargy, failure to thrive,
recurrent vomiting, dehydration which leads to profound metabolic
acidosis, respiratory distress, hypotonia and death if not recognized.
Complications of acute episodes can include metabolic stroke, extrapyramidal
signs, dystonia and bilateral lucencies of globus pallidus. Survivors
may have significant neurological damage. Renal failure may appear
during childhood. Clinical spectrum is wide, ranging from fatal neonatal
disease to asymptomatic individuals. Patients do not have to have
clinical crises in order to have neurological or other organ compromise.
|Natural history without treatment
||Variable depending on the enzyme defect and the patient. Some will
die as a neonate, others will survive with deficits and a few others
will remain asymptomatic.
|Natural history with treatment
|| About 60% of patients die within the first year of
life and of those that survive, 40% are distinctly developmentally
impaired. Age of onset of symptoms can help prognosticate –
those with later onset tend to have a more benign course. Liver and
liver/kidney transplant are one treatment option. However, liver transplants
have significant preoperative risk and there is documentation of neurological
problems after transplant despite improved biochemical values. Renal
transplants have shown good response with drops in methylmalonic acid
levels, normalization of the diet and absence of acute episodes of
metabolic decompensation. However, the effect of any type of transplant
is limited because the MMA enzyme is in all tissues and the transplants
do not affect the levels made in the cerebro-spinal fluid and brain.
|| Protein restricted diet, OH-Cbl injections, carnitine supplementation
and oral antibiotic therapy to decrease gut production of propionate.
Special medical foods (formula) deficient in methionine, threonine,
valine, isoleucine, odd chain fatty acids and cholesterol. Liver transplant
and liver/kidney transplant.
||Most patients have no obvious dysmorphic features. Some patients,
in whom there is known consanguinity, have had associated birth defects,
congenital heart defects, hydronephrosis and facial dysmorphisms.
|| Autosomal recessive
|General population incidence
||Liver, kidneys, cerebrospinal fluid, brain
|| Catalyzes methylmalonyl-CoA to succinyl-CoA
||Increased methylmalonic acid in blood and urine.
|DNA testing available
||Sequencing available internationally
|DNA testing detail
|| Possible via enzyme assay on amniocytes or CVS..
|| Elevated C3 propionyl carnitine, elevated C4 DC methylmalonyl carnitine.
Organic Acidemia Association
Save Babies through Screening Foundation