Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation
硫胺素治疗可恢复溶质载体家族19成员2(SLC19A2)基因突变所致的永久性新生儿糖尿病患儿的胰岛素分泌
Chengjun Sun
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorZhou Pei
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorMiaoying Zhang
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorBijun Sun
The Molecular Genetic Diagnosis Center, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorLin Yang
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
The Molecular Genetic Diagnosis Center, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorZhuhui Zhao
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorRuoqian Cheng
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorCorresponding Author
Feihong Luo
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Correspondence
Feihong Luo, Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, 399 Wanyuan Road, Minghang, Shanghai 201102, China.
Tel: +86 21 64931226
Fax: +86 21 64931901
Email: [email protected]
Search for more papers by this authorChengjun Sun
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorZhou Pei
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorMiaoying Zhang
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorBijun Sun
The Molecular Genetic Diagnosis Center, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorLin Yang
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
The Molecular Genetic Diagnosis Center, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorZhuhui Zhao
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorRuoqian Cheng
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorCorresponding Author
Feihong Luo
Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China
Correspondence
Feihong Luo, Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, 399 Wanyuan Road, Minghang, Shanghai 201102, China.
Tel: +86 21 64931226
Fax: +86 21 64931901
Email: [email protected]
Search for more papers by this authorAbstract
enBackground
Solute carrier family 19 member 2 (SLC19A2) gene deficiency is one of the causes of permanent neonatal diabetes mellitus (PNDM) and can be effectively managed by thiamine supplementation. Herein we report on a male patient with a novel SLC19A2 mutation and summarize the clinical characteristics of patients with SLC19A2 deficiency.
Methods
The genetic diagnosis of the patient with PNDM was made by sequencing and quantitative polymerase chain reaction. The clinical characteristics of PNDM were summarized on the basis of a systematic review of the literature.
Results
The patient with PNDM had c.848G>A (p.W283X) homozygous mutation in SLC19A2. His father had a wild-type SLC19A2 (c.848G) and his mother was c.848G/A heterozygous. The patient and his father both had a diploid genotype (c.848A/A and c.848G/G). After oral thiamine administration, the patient's fasting C-peptide levels increased gradually, and there was a marked decrease in insulin requirements. A search of the literature revealed that thiamine treatment was effective and improved diabetes in 63% of patients with SLC19A2 deficiency.
Conclusions
A novel SLC19A2 mutation (c.848G>A; p.W283X) was identified, which was most likely inherited as segmental uniparental isodisomy. Insulin insufficiency in PNDM caused by SLC19A2 deficiency can be corrected by thiamine supplementation. The differential diagnosis of SLC19A2 deficiency should be considered in children with PNDM accompanied by anemia or hearing defects to allow for early treatment.
摘要
zh背景
溶质运载蛋白家族19成员2(solute carrier family 19 member 2, SLC19A2)基因缺陷是永久性新生儿糖尿病(permanent neonatal diabetes mellitus, PNDM)的病因之一, 通过补充维生素硫胺素(维生素B1)能够有效治疗该病。本研究报道一例携带SLC19A2新突变的男性患者并对同类患者的临床表现进行总结。
方法
通过测序和荧光定量PCR对该例PNDM患儿进行遗传学诊断。通过系统性文献复习总结此类PNDM患者的临床表现。
结果
该PNDM患儿携带SLC19A2基因的c.848G > A(p.W283X)纯合突变。其父亲的SLC19A2基因该位点(c.848G)为正常的野生型, 其母亲为c.848G/A杂合携带者。患儿及其父亲的基因都是二倍体基因型(c.848A/A and c.848G/G)。该患者的空腹C肽在接受了维生素B1口服治疗后逐渐提高、同时胰岛素需要量显著下降。文献复习发现维生素B1可在63%的SLC19A2基因缺陷患者中有效治疗糖尿病。
结论
本研究发现了一个以节段单亲同源二倍体为遗传方式的SLC19A2新突变c.848G > A (p.W283X)。在SLC19A2缺陷所致的永久性新生儿糖尿病中, 维生素B1的治疗多有显著疗效。在临床上发现PNDM合并贫血或听力损害应着重鉴别SLC19A2缺陷并及时治疗。
Supporting Information
| Filename | Description |
|---|---|
| Supportinginformation.xlsxExcel 2007 spreadsheet , 26.5 KB | Table S1. Primer sequences. Table S2. Clinical information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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