Methylmalonic acidaemia (MMA)

3 year old female child came with developmental delay, lethargy, seizures and hypoglycemia, MRI brain T2 weighted image at the level of basal ganglia showing bilateral symmetrical hyperintensities in globi pallidi.

MMA encompasses a heterogeneous group of disorders characterized by accumulation of methylmalonic acid and its by-products in biological fluids. These disorders are due to a deficiency of the adenosylcobalamin-dependent enzyme methylmalonyl-CoA mutase (apoenzyme deficiency), a defect in intracellular cobalamin metabolism (coenzyme deficiency), transcobalamin II deficiency, intrinsic factor deficiency, or dietary cobalamin deficiency, which is found in vegetarians. The incidence, as derived form a neonatal screening program, is one in 48,000 live births (6). The actual occurrence, however, is estimated to be one in 25,000 live births.

CT and MR imaging of the brain typically reveal atrophy, delay in myelination, and abnormalities in the basal ganglia, predominantly in the globi pallidi. The globi pallidi are particularly sensitive to mitochondrial dysfunction, and are thus prime targets for injury. MR Spectroscopy may show elevated lactate levels either in CSF or in brain parenchyma i.e regions of infarcts. Differential diagnosis for bilateral globi pallidi lesions are HIE (hypoxic ischemic encephalopathy), kernicterus, mitochondrial encephalopathy etc.