Vuralli Dogus, Kosukcu Can, Taskiran Ekim, Simsek-Kiper Pelin Ozlem, Utine Gulen Eda, Boduroglu Koray, Alikasifoglu Ayfer, Alikasifoglu Mehmet
Division of Pediatric Endocrinology, Department of Pediatrics, Hacettepe University Medical School, Ankara, Turkey.
Department of Medical Genetics, Hacettepe University Medical School, Ankara, Turkey.
Mol Syndromol. 2020 Nov;11(4):207-216. doi: 10.1159/000510171. Epub 2020 Sep 16.
Several endocrine disorders have been defined in patients with Costello syndrome (CS). In this report, we describe a patient with CS accompanied by a clinical picture of hyperinsulinemic hypoglycemia responsive to diazoxide treatment. A 41-day-old female patient with a birth weight of 3,600 g was referred for atypical facial features and swallowing dysfunction. She had a weight of 4,000 g (-0.8 SDS), a length of 50 cm (-2.4 SDS), and a head circumference of 38 cm (0.2 SDS). The clinical findings were suggestive of a genetic syndrome, mainly a RASopathy or Beckwith-Wiedemann syndrome. Whole exome sequencing revealed a de novo heterozygous missense variant in the (NM_001130442) gene in exon 2: c.35G>C; p.(Gly12Ala), establishing the molecular diagnosis of CS. The patient developed symptomatic hypoglycemia (jitteriness and sweating) at the age of 13 months. The patient's serum glucose was 38 mg/dL with simultaneous serum insulin and C-peptide levels, 2.8 μIU/mL and 1.8 ng/mL, respectively. Hyperinsulinism was suspected, and an exaggerated glucose response was detected in a glucagon test. Blood glucose monitoring indicated episodes of fasting hypoglycemia and postprandial hyperglycemia. Diazoxide of 10 mg/kg/day was initiated in 3 doses for hyperinsulinemic hypoglycemia, which resolved without new episodes of postprandial hyperglycemia. The patient deceased at the age of 17 months due to cardiorespiratory failure in the course of severe pneumonia complicated with pulmonary hypertension and hypertrophic cardiomyopathy. Several genetic syndromes including CS are associated with endocrinologic manifestations including abnormal glucose homeostasis. Although the frequency and underlying mechanisms leading to hyperinsulinemic hypoglycemia are yet unknown, hypoglycemia in CS responds well to diazoxide.
科斯特洛综合征（CS）患者中已发现几种内分泌紊乱情况。在本报告中，我们描述了一名患有CS的患者，伴有对二氮嗪治疗有反应的高胰岛素血症性低血糖的临床表现。一名出生体重3600g的41日龄女性患者因非典型面部特征和吞咽功能障碍前来就诊。她体重4000g（-0.8 SDS），身长50cm（-2.4 SDS），头围38cm（0.2 SDS）。临床检查结果提示为一种遗传综合征，主要是RAS病或贝克威思-维德曼综合征。全外显子组测序显示在第2外显子的 （NM_001130442）基因中有一个新发杂合错义变异：c.35G>C；p.（Gly12Ala），从而确立了CS的分子诊断。该患者在13个月大时出现症状性低血糖（震颤和出汗）。患者血清葡萄糖为38mg/dL，同时血清胰岛素和C肽水平分别为2.8μIU/mL和1.8ng/mL。怀疑有高胰岛素血症，在胰高血糖素试验中检测到葡萄糖反应增强。血糖监测显示有空腹低血糖和餐后高血糖发作。开始以10mg/kg/天的剂量分3次给予二氮嗪治疗高胰岛素血症性低血糖，低血糖得到缓解，且未出现新的餐后高血糖发作。该患者在17个月大时因严重肺炎并发肺动脉高压和肥厚型心肌病导致心肺衰竭而死亡。包括CS在内 的几种遗传综合征与内分泌表现有关，包括葡萄糖稳态异常。虽然导致高胰岛素血症性低血糖的频率和潜在机制尚不清楚，但CS中的低血糖对二氮嗪反应良好。
