The clinical picture has a high variability, and
asymptomatic children with mutase apoenzyme deficiency have been identified
through newborn screening. Although the signs in symptomatic children are
basically similar to those of Propionic Acidemia, complications and
prognosis are worse in MAA. In 80%, manifestation of mut0 patients
occurs in the first week of life and the remainder by 6 months of life. In
contrast, mut- and cobalamin disorder patients most often
present after the first month of life. The most common signs and symptoms at
onset after a period of normal feeding are lethargy or coma, poor feeding
with failure to thrive, recurrent vomiting with dehydration,
hepatosplenomegaly, respiratory distress, and muscular hypotonia. MMA caused
by a cobalamin-related defect usually has onset later in childhood or
adolescence, starting with decreased lower leg sensitivity, thrombosis
secondary to persistent homocystinuria, and progressive myopathy leading to
chronic gait disturbances, which may not be irreversible. The majority of
patients present with metabolic acidosis with a blood pH less than 6.9 and
bicarbonate concentrations as low as 5 mmol/l. Ketonemia and ketonuria,
hyperammonemia, anemia, leukopenia, and thrombocytopenia are found in more
than 50% and hypoglycemia in 40% of the patients at presentation.
Hyperglycinemia has been reported in some patients. All patients with
isolated MMA have in common the high plasma and urine concentrations of MMA,
with urine concentrations up to 1000 times higher than normal. Infections
and high-protein diet are known triggers for acute exacerbation, and many
children with MMA may die in the first weeks of life, often before a
diagnosis has been established secondary to ketoacidosis and/or
hyperammonemia. The risk is significantly lower in MMA resulting from
cobalamin deficiency. The median life expectancy for mut0 patients is
approximately 6 years. Mental retardation, seizures, and stroke are common
features in MMA. The reasons for increased risk for stroke remain to be
determined, but several hypotheses exist: severe acidosis may result in
reduced cerebral blood flow secondary to hypocapnia or direct toxicity to
the brain (glial and neuronal cells) from MMA and odd-chain fatty acids, or
iatrogenic by treatment with high doses of cyanocobalamin, which is
metabolized to the highly toxic cyanide. A stroke should always be excluded
in MMA patients with acute onset of dystonia, dysarthria, dysphagia, or
choreoathetosis. Acute exacerbation requires symptomatic treatment
(rehydration, acid-base correction) and parenteral hyperalimentation with
minimal amounts of proteins and high doses of vitamin B12
and l-carnitine. Hemoor peritoneal dialysis may be required to correct
hyperammonemia effectively. Long-term treatment consists of a low-protein
diet and supplements of vitamin B12 and l-carnitine. Often
chronic bicarbonate supplements are required to correct the metabolic
acidosis. High forehead, epicanthal folds, broad nasal bridge, long
philtrum, and a triangular mouth are the features responsible for facial
dysmorphism. Skin lesions similar to acrodermatitis enteropathica have been
described repeatedly. Chronic tubulointerstitial nephritis with progressive
decline of renal function is a frequent long-term complication (20-60%
of adolescents with MMA) and may require either hemodialysis or kidney
transplantation.