Lili Liang1, Ruixue Shuai1, Yue Yu1, Wenjuan Qiu1, Linghua Shen2, Shengnan Wu2, Haiyan Wei2, Yongxing Chen2, Chiju Yang3, Peng Xu3, Xigui Chen3, Hui Zou4, Jizhen Feng5, Tingting Niu6, Haili Hu7, Jun Ye1, Huiwen Zhang1, Deyun Lu1, Zhuwen Gong1, Xia Zhan1, Wenjun Ji1, Yongguo Yu1, Xuefan Gu1, Lianshu Han8. 1. Department of Pediatric Endocrinology/Genetics, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Department of Pediatric Endocrinology and Genetics, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China. 3. Center of Neonatal Disease Screening, Jining Maternal and Child Health Care Hospital, Jining, China. 4. Center of Neonatal Disease Screening, Jinan Maternal and Child Health Care Hospital, Jinan, China. 5. Center of Neonatal Disease Screening, Shijiazhuang Maternal and Child Health Care Hospital, Shijiazhuang, China. 6. Center of Neonatal Disease Screening, Shandong Maternal and Child Health Care Hospital, Jinan, China. 7. Center of Neonatal Disease Screening, Hefei Maternal and Child Health Care Hospital, Hefei, China. 8. Department of Pediatric Endocrinology/Genetics, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. hanlianshu@xinhuamed.com.cn.
Abstract
BACKGROUND: Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype. METHODS: Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant. RESULTS: Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients. CONCLUSION: Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.
BACKGROUND: Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype. METHODS: Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant. RESULTS: Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients. CONCLUSION: Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.
Entities:
Keywords:
Genotype; MMUT gene; Methylmalonic acidemia; Mutation; Newborn screening; Tandem mass spectrometry
Authors: Lisa C Worgan; Kirsten Niles; Jamie C Tirone; Adam Hofmann; Andrei Verner; Alya'a Sammak; Terrence Kucic; Pierre Lepage; David S Rosenblatt Journal: Hum Mutat Date: 2006-01 Impact factor: 4.878
Authors: Patrick Forny; Anne-Sophie Schnellmann; Celine Buerer; Seraina Lutz; Brian Fowler; D Sean Froese; Matthias R Baumgartner Journal: Hum Mutat Date: 2016-05-23 Impact factor: 4.878
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