晚发型甲基丙二酸尿症cblC型三例临床特点和基因分析

Abstract

Objective To investigate the gene mutations, clinical manifestations, imaging features, treatments and pathophysiologic mechanisms of the patients with late-onset methylmalonic aciduria, cblC type. Methods Two boys and one girl were diagnosed as late-onset combined methylmalonic aciduria and homocystinuria cblC type by MMCHC gene sequencing at their 13, 12 and 17 years old, respectively. Their clinical manifestations, imaging features, laboratory findings and responses of treatment were reviewed. Results The MMACHC gene mutations in case 1 were c.482G>A and c.609G>A. For case 2, they were c.482G>A and c.658_660delAAG. And for case 3, they were c.482G>A and IVS1,+1G>A. The three patients presented with heterogeneous clinical pictures, including mental disorder, cognitive impairment, epilepsy, ataxia and signs of pyramidal damage and peripheral nerve injuries. Personal histories of all these 3 patients showed dislike for high-protein foods, such as meat, eggs, milk and tofu. Cerebral atrophy was visible in magnetic resonance imaging (MRI) scans of three cases. In addition, bilateral cerebellar cortex abnormalities were also found in one patient. Conclusions The cerebral cortex, pyramidal system, extrapyramidal system, peripheral nerve (including motor nerve, sensory nerve and autonomic nerve) can be widely involved in this disease. This disease should be suspected when the young patients present with abnormal gait, epilepsy, rapidly progressive dementia or mental disorder and dislike for high-protein food, such as meat, eggs, tofu. Brain MRI showing encephalatrophy prompts the diagnosis. Key words: Amino acid metabolism, inborn errors; Homocystinuria; Carrier proteins; Magnetic resonance imaging