Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a known INS gene mutation.
Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a known INS gene mutation.
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DOI：
10.1111/pedi.12335
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发表时间：
2016-11
影响因子：
3.4
通讯作者：
Crimmins NA
中科院分区：
文献类型：
--
作者：
Wasserman H;Hufnagel RB;Miraldi Utz V;Zhang K;Valencia CA;Leslie ND;Crimmins NA
儿童期糖尿病相关白内障的患病率低于 1%。当白内障发生时，通常发生在青春期女性身上，并伴有长期症状和严重高血糖。白内障不是单基因糖尿病的典型特征。我们报告了一例先前健康的六岁白人男性，他患有双侧获得性白内障，随后被诊断患有新发糖尿病。就诊时的其他症状包括数年多尿和烦渴病史、轻度肝肿大和身材矮小。相关的负面影响包括黑棘皮症、脂肪萎缩、耳聋、肌肉无力或神经病。诊断时 HbA1c 显着升高（>14%，129.5mmol/mol），但没有酮症证据。自身抗体检测呈阴性。莫里亚克综合征（身材矮小、肝肿大）以及获得性白内障的特征表明，长期存在高血糖，并有足够的胰岛素产生来防止酮的产生和糖尿病酮症酸中毒的发展。进行了全外显子组测序，并鉴定了 INS 基因的从头杂合突变（c.94G>A；p.Gly32Ser）。 INS 基因突变是永久性新生儿糖尿病的常见原因，但儿童抗体阴性糖尿病的罕见原因。重要的是，INS 基因突变此前并未与获得性白内障相关。了解糖尿病的单基因病因使临床医生能够针对糖尿病相关合并症进行定制咨询和筛查。总之，该病例强调需要考虑对抗体阴性糖尿病儿科患者进行单基因糖尿病检测，特别是 INS 基因突变，特别是在诊断时存在长期高血糖并发症的情况下。
The prevalence of diabetes-related cataracts during childhood is less than 1%. When cataracts occur, it is often in adolescent females with prolonged symptoms and significant hyperglycemia. Cataracts are not a classic feature of monogenic diabetes. We report a case of a six year old previously healthy Caucasian male who presented with bilateral acquired cataracts and was subsequently diagnosed with new onset diabetes. Additional symptoms at presentation included a several year history of polyuria and polydipsia, mild hepatomegaly, and short stature. Pertinent negatives include acanthosis nigricans, lipoatrophy, deafness, muscle weakness, or neuropathy. HbA1c was significantly elevated at diagnosis (>14%, 129.5mmol/mol) without evidence of ketosis. Autoantibody testing was negative. Features of Mauriac Syndrome (short stature, hepatomegaly) as well as acquired cataracts indicated long standing hyperglycemia with sufficient insulin production to prevent ketone production and development of diabetic ketoacidosis. Whole exome sequencing was conducted and a de novo heterozygous mutation in the INS gene (c.94G>A; p.Gly32Ser) was identified. INS gene mutations are common causes of permanent neonatal diabetes but rare causes of antibody-negative diabetes in children. Importantly, INS gene mutations have not been previous associated with acquired cataracts. Knowledge of a monogenic cause of diabetes allows clinicians to tailor counseling and screening of diabetes related co-morbidities. In summary, this case highlights the need to consider testing for monogenic diabetes, specifically INS gene mutations, in pediatric patients with antibody-negative diabetes, especially if complications of prolonged hyperglycemia are present at diagnosis.