National Institute of Child Health, Karachi, Pakistan.
Institute of Biomedical and Clinical Science, University of Exeter College of Medicine and Health, Exeter, UK.
J Pediatr Endocrinol Metab. 2021 Jun 30;34(9):1095-1103. doi: 10.1515/jpem-2020-0669. Print 2021 Sep 27.
To review the data of infants and children with suspected monogenic diabetes who underwent genetic testing.
Monogenic diabetes is a rare form of diabetes resulting from mutations in a single gene. It can be caused by dominant as well as recessive modes of inheritance. In a country like Pakistan where interfamily marriages are common the incidence of genetic disorders is increased. As Pakistan a resource-poor country, the diagnosis of insulin-dependent diabetes is often delayed and a genetic diagnosis of monogenic diabetes is extremely difficult. Children with clinical diagnosis of monogenic and syndromic diabates were recruited and blood samples were sent for genetic analysis.
One thousand sixty four new cases diagnosed with type 1 diabetes were registered at the National Institute of Child Health, Karachi, in the last 10 years. Of these 39 patients were selected for genetic testing who were diagnosed with diabetes/had a sibling diagnosed with diabetes before the age of nine months (n = 27) or had extra pancreatic features ( n= 12). We identified mutations in 18/27 cases diagnosed with diabetes before nine months of age. The most common genetic subtype was WolcottRallison syndrome caused by mutations (seven cases). mutations were identified in two cases, mutations were identified in four cases from three families, and mutations were each identified in two cases, and one mutation was identified in one case. A genetic diagnosis was made in 12/12 children from six families with diabetes diagnosed after the age of nine months who had extrapancreatic features. Six patients had genetically confirmed Wolfram syndrome (), three had thiamine-responsive megaloblastic anemia () and three were diagnosed with histocytosis lymphadenopathy plus syndrome ().
Genetic testing is essential to confirm a diagnosis of monogenic diabetes which guides clinical management and future counselling. Our study highlights the importance of diagnosing monogenic diabetes in the largely consanguineously-married population of Pakistan.
回顾接受基因检测的疑似单基因糖尿病婴儿和儿童的数据。
单基因糖尿病是一种由单个基因突变引起的罕见糖尿病形式。它可以由显性和隐性遗传方式引起。在巴基斯坦这样一个跨国婚姻常见的国家，遗传疾病的发病率增加。由于巴基斯坦是一个资源匮乏的国家，胰岛素依赖型糖尿病的诊断常常被延迟，单基因糖尿病的基因诊断极其困难。对具有单基因和综合征性糖尿病临床诊断的儿童进行招募，并将血液样本送检进行基因分析。
在过去 10 年里，卡拉奇国家儿童健康研究所共登记了 1064 例新诊断的 1 型糖尿病患者。在这些患者中，有 39 例被选择进行基因检测，这些患者被诊断为糖尿病/在 9 个月前兄弟姐妹被诊断为糖尿病（n=27）或有胰腺外特征（n=12）。我们在 27 例 9 个月前被诊断为糖尿病的患者中发现了突变。最常见的遗传亚型是沃科特-拉利森综合征，由突变引起（7 例）。在 2 例患者中发现了突变，在来自 3 个家庭的 4 例患者中发现了突变，在 2 例患者中发现了突变和突变，在 1 例患者中发现了突变。在 6 个有胰腺外特征且在 9 个月后被诊断为糖尿病的家庭的 12 例儿童中做出了基因诊断。6 例患者患有遗传证实的沃尔弗拉姆综合征（），3 例患有硫胺素反应性巨幼细胞性贫血（），3 例患有组织细胞增多症伴淋巴结病综合征（）。
基因检测对于确认单基因糖尿病的诊断至关重要，这可以指导临床管理和未来的咨询。我们的研究强调了在巴基斯坦这个主要是近亲结婚的人群中诊断单基因糖尿病的重要性。
