A clinical and gene analysis of late-onset combined methylmalonic aciduria and homocystinuria, cblC type, in China.

BACKGROUND: Combined methylmalonic aciduria and homocystinuria, cblC type (cblC disease), is the most common inborn disorder of cobalamin metabolism. This disorder is caused by MMACHC gene mutations, and it is usually diagnosed in the early neonatal period. Late-onset cblC is rare and difficult to recognize due to a wide diversity of symptoms.
METHODS: Three cases with late-onset combined methylmalonic aciduria and homocystinuria, cblC type, are reported; patients' clinical presentation, imaging and MMACHC gene mutations were analyzed.
RESULTS: The age of onset in the three patients was 22 years, 40 years and 7 years of age. Two of the patients had MMACHC gene mutations heterozygous for c.609G>A and c.482G>A (case 1 and case 3). The other patient (case 2) presented with gene mutations heterozygous for c.609G>A and c.1A>G. The three patients presented with a heterogeneous clinical picture, including cognitive impairment, epilepsy, ataxia, pyramidal and peripheral nerve symptoms. Cerebral atrophy and bilateral hyperintensity in the deep white matter were visible in MRI scans of the patients' brains; those were significant findings in the three patients with late-onset cblC disease. In contrast with previous reports, bilateral cerebellar cortex abnormalities were also found in one patient (case 2).
CONCLUSION: Although its occurrence is rare, late-onset combined methylmalonic aciduria and homocystinuria, cblC type, should be considered in making a differential diagnosis in patients who present with neurological symptoms that are not consistent with common neurological diseases, especially when cognition, the pyramidal tract and peripheral nerves are involved.