BACKGROUND AND PURPOSE: Combined methylmalonic aciduria and homocystinuria
(MMA-HC) is caused by impaired hepatic conversion of dietary cobalamin to m
ethylcobalamin and adenosylcobalamin, resulting in decreased activity of me
thylmalonyl-CoA mutase and methionine synthase. Patients with the early-ons
et variety present within 12 months of age with severe neurologic, hematolo
gic, and gastrointestinal abnormalities. We describe the neuroradiologic fe
atures of early-onset MMA-HC and discuss related pathophysiological mechani
sms.
METHODS: Twelve infants with hypotonia, failure to thrive, poor feeding, an
d hematologic abnormalities were diagnosed with MMA-HC on the basis of a ty
pical plasmatic and urinary metabolic profile and enzyme activity in fibrob
lastic cultures. Complementation studies were performed in two cases, and y
ielded a CMC result. MR imaging was performed at presentation in four cases
and later in the others. All patients showed prompt biochemical improvemen
t with intramuscular hydroxocobalamin administration, and most had moderate
neurologic improvement.
RESULTS: Diffuse supratentorial white matter edema and dysmyelination was t
he typical MR picture at presentation, whereas white matter bulk loss chara
cterized later stages of the disease. Nucleocapsular areas of gliosis were
an additional finding in one case. One patient had tetraventricular hydroce
phalus at presentation.
CONCLUSION: White matter damage is probably caused by reduced methyl group
availability and nonphysiological fatty acids toxicity, whereas focal glios
is results from homocysteine-induced toxicity to the endothelium, Hydroceph
alus may result from diffuse intracranial extracerebral arterial stiffness,
known as reduced arterial pulsation hydrocephalus. MR imaging features at
presentation and at follow-up are nonspecific.