RESUMO
Objective:To analyze the disease spectrum of lysosomal storage disorders(LSDs) and explore the prevalent distributions of different LSD types in one center in Shanghai.Methods:A retrospective analysis was made.A total of 5 476 suspected LSD patients, including 3 415 males and 2 061 females, with a median age of 4 years(1 day to 72 years), were collected from Xinhua Hospital, Shanghai Jiaotong University School of Medicine from August 2008 to May 2022.The activity of different lysosomal enzymes was detected by fluorescent and biochemical methods.Results:A total of 1 520 patients were diagnosed with LSDs, including 972 males and 548 females, with a median age of 4 years(1 day to 59 years), involving 19 different subtypes.Mucopolysaccharidosis(MPS) was the most common type among LSDs, with a frequency of 45.46%(691/1 520), followed by sphingolipidoses [33.88%(515/1 520)] and glycogen storage disease type Ⅱ [16.05%(244/1 520)] successively.MPS Ⅱ was the most common type in MPS, with a frequency of 45.73%(316/691), followed by MPS ⅣA [22.87%(158/691)]. Niemann-Pick A/B, Gaucher, and Krabbe diseases were common in Sphingolipidoses patients, with frequencies of 37.09%(191/515), 34.37%(177/515), and 10.29%(53/515), respectively.Conclusions:LSDs are common genetic metabolic diseases, especially MPS and sphingolipidoses.Newborn screening for LSDs should be carried out timely so that the patients can be treated early and their prognosis can be improved.
RESUMO
Objective:Nuclear magnetic resonance spectroscopy (NMR) was used to detect the species and content of metabolites in urine of patients with inherited metabolic diseases, and to explore the application value of NMR technology in the diagnosis of inherited metabolic diseases.Methods:Urine samples were collected from 20 patients with inherited metabolic diseases diagnosed in Xinhua Hospital, Shanghai Jiaotong University School of Medicine from March to June 2019, including 9 cases of methylmalonic acidemia (MMA). NMR pulse length-based concentration determination and Gas chromatography mass spectrometry (GC/MS) semi-quantitative method were used to detect the composition of metabolites in urine samples of patients with inherited metabolic diseases, and the levels of abnormal metabolites in the two methods were analyzed.Results:NMR technology can detect the levels of characteristic metabolites significantly increased in the urine of patients with MMA, isovalerinemia, glutaric acidemia, propionic acidemia, 3-methylcrotonyl-CoA carboxylase deficiency, ornithine carbamyltransferase deficiency, Citrin deficiency, Canavan disease, tyrosinemia and lysinuria protein intolerance. The average is 8 times of the upper limit of the reference value, and the highest is 545 times. Compared to GC/MS, NMR technology can detect the levels of various metabolites such as organic acids, amino acids and sugars. In 9 cases of untreated MMA,the median levels of methylmalonic acid and 3-hydroxypropionic acid in NMR [1 800 (180-12 000) and 50 (0-270) mmol/mol Cr] were higher than the reference values (0-31, 0-35). The median levels of methylmalonic acid and methylmalonic acid in GC/MS [136.56 (43.79-518.67) and 4.87 (1.52-7.52)] were higher than the reference values (0-4 and 0-0.7).Conclusions:NMR and GC/MS technologies are specific for the diagnosis of organic acidemia. The primary component detected by GC/MS is organic acid. NMR technology can break through this limitation and measure the level of various metabolites in urine, which provides a more theoretical basis for the diagnosis and research of inherited metabolic disease.