Department of General Paediatrics, Neonatology and Paediatric Cardiology, Medical Faculty, University Children's Hospital Düsseldorf, Düsseldorf, Germany.
Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Eur J Endocrinol. 2019 Aug;181(2):121-128. doi: 10.1530/EJE-19-0119.
Genetic aetiology remains unknown in up to 50% of patients with persistent hyperinsulinaemic hypoglycaemia (HH). Several syndromes are associated with HH. We report Rubinstein-Taybi syndrome (RSTS) as one of the possible causes of persistent HH. Early diagnosis and treatment of HH is crucial to prevent hypoglycaemic brain injury.
Four RSTS patients with HH were retrospectively analysed.
Genetic investigations included next-generation sequencing-based gene panels and exome sequencing. Clinical characteristics, metabolic profile during hypoglycaemia and treatment were reviewed.
Disease-related EP300 or CREBBP variants were found in all patients, no pathogenic variants were found in a panel of genes associated with non-syndromic HH. Two patients had classic manifestations of RSTS, three had choanal atresia or stenosis. Diagnosis of HH varied from 1 day to 18 months of age. One patient was unresponsive to treatment with diazoxide, octreotide and nifedipine, but responded to sirolimus. All required gastrostomy feeding.
Given the rarity of RSTS (1:125 000) and HH (1:50 000), our observations indicate an association between these two conditions. We therefore recommend that clinicians should be vigilant in screening for HH in symptomatic infants with RSTS. In children with an apparent syndromic form of HH, RSTS should be considered in the differential diagnosis.
在持续高胰岛素血症性低血糖症（HH）患者中，高达 50%的患者病因仍未知。一些综合征与 HH 相关。我们报告 Rubinstein-Taybi 综合征（RSTS）是 HH 持续存在的可能原因之一。早期诊断和治疗 HH 对于预防低血糖性脑损伤至关重要。
回顾性分析了 4 例 HH 的 RSTS 患者。
遗传研究包括基于下一代测序的基因面板和外显子组测序。回顾了临床特征、低血糖期间的代谢谱和治疗情况。
所有患者均发现与疾病相关的 EP300 或 CREBBP 变异，在与非综合征性 HH 相关的基因面板中未发现致病性变异。2 例患者有典型的 RSTS 表现，3 例患者有后鼻孔闭锁或狭窄。HH 的诊断年龄从 1 天至 18 个月不等。1 例患者对二氮嗪、奥曲肽和硝苯地平治疗无反应，但对西罗莫司有反应。所有患者均需要胃造口喂养。
鉴于 RSTS（1:125 000）和 HH（1:50 000）的罕见性，我们的观察结果表明这两种情况之间存在关联。因此，我们建议临床医生应警惕在有 RSTS 症状的婴儿中筛查 HH。对于表现出明显综合征形式 HH 的儿童，应考虑 RSTS 作为鉴别诊断。
