Pediatric Endocrinology Division, Children's Hospital, University of Bonn, Bonn, Germany.
Department of Neonatology, St. Marien-Hospital, Bonn, Germany.
Front Endocrinol (Lausanne). 2021 Apr 16;12:665336. doi: 10.3389/fendo.2021.665336. eCollection 2021.
Neonatal diabetes with congenital hypothyroidism (NDH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLI-similar 3 coding gene . Almost 20 patients have been reported to date, with significant phenotypic variability.
We describe a boy with a homozygous deletion (exons 5-9) in the gene, who presents novel clinical aspects not reported previously. In addition to neonatal diabetes, congenital hypothyroidism and other known multi-organ manifestations such as cholestasis and renal cysts, he suffered from hyporegenerative anemia during the first four months of life and presents megalocornea in the absence of elevated intraocular pressure. Compensation of partial exocrine pancreatic insufficiency and deficiencies in antioxidative vitamins seemed to have exerted marked beneficial impact on several disease symptoms including cholestasis and TSH resistance, although a causal relation is difficult to prove. Considering reports on persistent fetal hemoglobin detected in a few children with mutations, the transient anemia seen in our patient may represent a further symptom associated with either the defect itself or, secondarily, micronutrient deficiency related to exocrine pancreatic deficiency or cholestasis.
Our report expands the phenotypic spectrum of patients with mutations and adds important information on the clinical course, highlighting the possible beneficial effects of pancreatic enzyme and antioxidative vitamin substitutions on characteristic NDH syndrome manifestations such as TSH resistance and cholestasis. We recommend to carefully screen infants with mutations for subtle biochemical signs of partial exocrine pancreatic deficiency or to discuss exploratory administration of pancreatic enzymes and antioxidative vitamins, even in case of good weight gain and fecal elastase concentrations in the low-to-normal range.
伴先天性甲状腺功能减退的新生儿糖尿病（NDH）综合征是一种由 GLI-相似 3 编码基因突变引起的罕见疾病，几乎有 20 例患者被报道，具有显著的表型变异性。
我们描述了一个男孩，携带 GLI-相似 3 基因的纯合缺失（外显子 5-9），他表现出以前未报道过的新的临床特征。除了新生儿糖尿病、先天性甲状腺功能减退症和其他已知的多器官表现，如胆汁淤积和肾囊肿外，他在生命的前四个月患有再生障碍性贫血，并且在没有眼压升高的情况下出现巨角膜。部分外分泌胰腺功能不全和抗氧化维生素缺乏的代偿似乎对包括胆汁淤积和 TSH 抵抗在内的几种疾病症状产生了显著的有益影响，尽管很难证明因果关系。考虑到一些携带 GLI-相似 3 基因突变的儿童中存在持续胎儿血红蛋白的报道，我们患者的短暂性贫血可能代表与 GLI-相似 3 缺陷本身或继发于与外分泌胰腺缺乏或胆汁淤积相关的微量营养素缺乏相关的另一种症状。
我们的报告扩展了 GLI-相似 3 基因突变患者的表型谱，并提供了关于临床过程的重要信息，突出了胰腺酶和抗氧化维生素替代对 TSH 抵抗和胆汁淤积等特征性 NDH 综合征表现的可能有益影响。我们建议仔细筛查携带 GLI-相似 3 基因突变的婴儿是否存在轻微的外分泌胰腺缺乏的生化迹象，或者讨论探索性使用胰腺酶和抗氧化维生素，即使在体重增加良好且粪便弹性蛋白酶浓度处于低至正常范围内的情况下。
