Homocystinuria-megaloblastic anemia cblD type (HMAD) is an autosomal recessive metabolic disorder of cobalamin (cbl; vitamin B12) metabolism. Affected individuals present in infancy or early childhood with neurologic abnormalities, including developmental delay, impaired gross motor skills, dystonia or spastic ataxia, poor speech, and cerebral or cerebellar atrophy on brain imaging. Additional more variable features may include nystagmus, poor eye contact, hypotonia, and seizures. Laboratory studies show elevated plasma homocystine, low methionine, and megaloblastic anemia; methylmalonic acid levels are normal. Treatment with betaine, folic acid, and OH-cobalamin results in some improvement of the clinical and biochemical abnormalities (Suormala et al., 2004).
See also HMAE (236270) and HMAG (250940). [from
OMIM]