Gaucher disease (GD) is an inherited metabolic disorder that involves accumulation of glycolipid glucocerebroside in monocyte–macrophage cells, which can result in multiple organ damage. Enzyme replacement and substrate reduction therapies have improved the potential for early diagnosis and treatment. Determining the true incidence of this rare disease is critical for relevant policy establishment. Newborn screening allows for early diagnosis and an comparatively accurate incidence of GD. A fluorometric method to detect acid β-glucocerebrosidase (GBA) activity on a dried blood spot punch was developed. Validity and feasibility of the fluorometric method was demonstrated by examining 116 healthy controls, 19 confirmed GD patients and 19 obligate carriers. GBA activity was measured on dried blood spots of 80 855 newborns. Samples from positively screened newborns were reanalyzed by a leukocyte GBA activity test and GBA gene analysis. Plasma glucosylsphingosine level was determined as a biomarker of the pathophysiology of GD. GD patients were distinguished from healthy controls and obligate carriers using the fluorometric method. Mean GBA activity in newborn screening specimens was 145.69±44.76 μmol l−1 h−1 (n=80 844). Three children had low GBA activity, of which one child had low GBA activity on the second dried blood spot specimen. Leukocyte, genetic and biomarker analysis confirmed the diagnosis and indicated that this child was in the early stages of GD. In conclusion, the incidence of GD in Shanghai of China is approximately 1 in 80 855. Screening for GD by fluorometric analysis of GBA activity is an efficient and feasible technology in newborns.

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

Background: Cobalamin C deficiency (cblC) caused by the MMACHC mutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in Chinese cblC patients, its correlation with phenotype has not been delineated. Here we aim to investigate the factors affecting variable phenotypes and outcomes associated with the MMACHC c.609G > A homologous mutation in 149 Chinese cases to have implications for treatment and prevention. Methods: We assessed 149 cblC patients caused by MMACHC c.609G > A homozygous mutation. The clinical manifestations, complications, treatment, and outcomes were evaluated; 120 patients were followed-up till December 2019.

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