Clinical and Biochemical Studies on Chinese Patients With Methylmalonic Aciduria

Abstract

Methylmalonic aciduria is a common organic aciduria disease. Recently, gas chromatography-mass spectrometry has been used to diagnose methylmalonic aciduria in China. Often, however, the diagnosis of methylmalonic aciduria is delayed because of a lack of technical expertise and the limited experience of general clinicians in China. In this study, the natural history, clinical features, and outcome of 77 Chinese patients with methylmalonic aciduria were investigated. Of the 77 patients, 31 (40.3%) had isolated methylmalonic aciduria and 46 (59.7%) had methylmalonic aciduria combined with homocystinemia. Thus, we observed a higher rate of the combined disease than studies conducted in other countries, suggesting that it might be more common in China. Total plasma homocysteine measurement might enable differential diagnoses of methylmalonic aciduria to be distinguished. The clinical spectrum of these 77 patients with methylmalonic aciduria ranged from neonatal death and severe symptoms to benign asymptomatic organic aciduria. Neonatal and infantile onset, which was a characteristic of the majority of cases, was associated with a greater severity relative to later-onset cases. Among the 17 cases who had onset after 3 years of age, only 1 patient had isolated methylmalonic aciduria and 16 had combined methylmalonic aciduria and homocystinemia. Nine of the patients with combined methylmalonic aciduria and homocystinemia completely recovered and exhibited normal intelligence, whereas seven improved, with a mild handicap.

Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria

“…However, after treatment, five of them recovered and showed normal levels of intelligence, whereas the remaining three improved significantly, but with some residual handicap. 16 Among these eight late-onset cblC patients, seven patients (87.5%) were compound heterozygous for the c.482G4A mutation and the remaining one was compound heterozygous for the c.452A4G and c.609G4A mutations. Although one patient, who was homozygous for the c.482G4A mutation, presented with early-onset clinical symptoms (Table 4), the c.482G4A mutation was in general associated with the late-onset phenotype and a milder clinical presentation.…”

“…16,18 Among the 71 patients, 55 early-onset patients presented with the disease in the first year of life, eight late-onset patients showed symptoms after 4 years of age and the other eight patients presented with symptoms at an age between 1 and 4 years. 16,18 Information about age onset for 15 patients homozygous for the c.609G4A mutation was available (Table 4), including 12 early-onset patients and 3 patients presenting before the age of 4 years. The results suggest that the c.609G4A mutation may be associated with the early-onset phenotype.…”

“…The patients were from Beijing (n¼75), 16,[18][19] Taiwan (n¼2) and Shanghai (n¼2). Most patients (75 of 79) were Northern Chinese.…”

“…7 MMA is the most common symptomatic organic acidurias in China, 15 but the precise incidence of Chinese population remains unclear. In 2006, Yang et al 16 reported that the incidence of patients with combined MMA and HC among MMA patients was higher in China than in other countries, suggesting that combined MMA and HC might be more common in Chinese populations. However, in Taiwan, 14 MMA patients were detected in the expanded newborn screening program from 1321123 newborns, including 13 mut-type MMA and 1 cblC-type MMA, 17 which indicates that the mut-type MMA is more common than the cblC-type MMA in Southern Chinese.…”

Inborn Errors of Metabolism and Brain Involvement - 5 Years Experience from a Tertiary Care Center in South India

“…Chandler et al (2007) reports successful use of adenoviral mediated gene therapy for methylmalonic aciduria in murine models and human patients with MUT gene mutation. Yang et al (2006) and other authors report that in China methylmalonic acidurias is more commonly associated with homocysteinemia. Filippi et al (2010) (2003) and Rossi et al (2001) also describe neurological damage in MMA.…”