RT Journal Article
SR Electronic
T1 Early-onset Combined Methylmalonic Aciduria and Homocystinuria: Neuroradiologic Findings
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
SP 554
OP 563
VO 22
IS 3
A1 Rossi, Andrea
A1 Cerone, Roberto
A1 Biancheri, Roberta
A1 Gatti, Rosanna
A1 Schiaffino, Maria Cristina
A1 Fonda, Claudio
A1 Zammarchi, Enrico
A1 Tortori-Donati, Paolo
YR 2001
UL http://www.ajnr.org/content/22/3/554.abstract
AB BACKGROUND AND PURPOSE: Combined methylmalonic aciduria and homocystinuria (MMA-HC) is caused by impaired hepatic conversion of dietary cobalamin to methylcobalamin and adenosylcobalamin, resulting in decreased activity of methylmalonyl-CoA mutase and methionine synthase. Patients with the early-onset variety present within 12 months of age with severe neurologic, hematologic, and gastrointestinal abnormalities. We describe the neuroradiologic features of early-onset MMA-HC and discuss related pathophysiological mechanisms.METHODS: Twelve infants with hypotonia, failure to thrive, poor feeding, and hematologic abnormalities were diagnosed with MMA-HC on the basis of a typical plasmatic and urinary metabolic profile and enzyme activity in fibroblastic cultures. Complementation studies were performed in two cases, and yielded a CblC result. MR imaging was performed at presentation in four cases and later in the others. All patients showed prompt biochemical improvement with intramuscular hydroxocobalamin administration, and most had moderate neurologic improvement.RESULTS: Diffuse supratentorial white matter edema and dysmyelination was the typical MR picture at presentation, whereas white matter bulk loss characterized later stages of the disease. Nucleocapsular areas of gliosis were an additional finding in one case. One patient had tetraventricular hydrocephalus at presentation.CONCLUSION: White matter damage is probably caused by reduced methyl group availability and nonphysiological fatty acids toxicity, whereas focal gliosis results from homocysteine-induced toxicity to the endothelium. Hydrocephalus 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.