A study on a cohort of 301 Chinese patients with isolated methylmalonic acidemia

Abstract

Methylmalonic acidemia (MMA) is the most common organic acidemia in China. This study aimed to characterise the genotypic and phenotypic variabilities, and the molecular epidemiology of Chinese patients with isolated MMA. Patients (n = 301) with isolated MMA were diagnosed by clinical examination, biochemical assays, and genetic analysis. Fifty-eight patients (19.3%) were detected by newborn screening and 243 patients (80.7%) were clinically diagnosed after onset. Clinical onset ranged from the age of 3 days to 23 years (mean age = 1.01 ± 0.15 years). Among 234 MMA patients whose detailed clinical data were available, 170 (72.6%) had early onset disease (before the age of 1 year), and 64 (27.4%) had late-onset disease. The 234 MMA patients manifested with neuropsychiatric impairment (65.4%), haematological abnormality (31.6%), renal damage (8.5%), and metabolic crises (67.1%). Haematological abnormality was significantly more common in early-onset patients than that in late-onset patients. The incidence of metabolic crises was significantly high (P < 0.001) in patients with mut type than those with other types of isolated MMA. Variations (n = 122) were identified in MMUT, MMAA, MMAB, MMADHC, SUCLG1, and SUCLA2, of which 45 were novel. c.729_730insTT was the most frequent MMUT mutation, with a significantly higher frequency in our patients than that in 151 reported European patients. The frequency of c.914T>C in MMUT in our cohort was also higher than that in 151 European patients. MMUT mutations

Spectrum analysis of inborn errors of metabolism for expanded newborn screening in a northwestern Chinese population

“…Similar to the report by Hu et al 28 , in our population, c.323G>A was the most prevalent mutation in the MMUT gene. However, previous other studies have suggested that c.729_730insTT is the most common MMUT mutation in China 29,30 . This difference should be taken into account the small number of cases in this study and the impact of geographical differences.…”

A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients

“…Han et al described two patients, compound heterozygous condition with missense variants in combination with the c.1663G > A, one of which had mild hyperammonemia at presentation [17]. Kang et al also mentioned this mutation, however, without detailed description of the clinical information of the carrying patient [18]. Liu et al presented yet another case of compound heterozygous condition with a different mutation, who had a late symptomatic presentation at age 38 months with acute brain stem encephalitis and myelitis, a devastating complication of mut MMA [15].…”

“…In China, the most common mutations include c.729_730insTT(p.D244Lfs*39), c.1106G > A (p.R369H), c.323G > A (p.R108H), and c.1107dupT (p.T370Yfs*22) [8,14]. The c.1663G > A (p.A555T) mutation in the MMUT gene is relatively rare, which is so far reported only in a few cases [7,[15][16][17][18]. Limited information is available on the clinical and biochemical characteristics of patients carrying this mutation.…”

Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia

“…Metabolic therapy, including a high-calorie diet with special formula supplementation (no isoleucine, threonine, methionine, and valine), stopping protein intake and intramuscular cobalamin were provided to most patients. Treatment for the patients was then adjusted according to their response to vitamin B12 and other individual conditions 7 , 10 – 12 .…”