David Odeya, Barash Galia, Agur Rotem, Loewenthal Neta, Carmon Lior, Shaki David, Walker Dganit, Novoa Rosa, Haim Alon, Hershkovitz Eli
Pediatric Endocrinology Unit, Soroka University Medical Center, Beer Sheva, Israel.
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
J Clin Endocrinol Metab. 2021 Jan 23;106(2):e907-e916. doi: 10.1210/clinem/dgaa807.
The rare hypoparathyroidism-retardation-dysmorphism (HRD) syndrome (OMIM #241410) is caused by the mutated tubulin chaperone E (TBCE) gene. This gene encodes a critical protein in the microtubule assembly pathway.
To evaluate the endocrine profile of patients with HRD.
The study used a retrospective analysis of a large cohort of patients in a single university medical center. Sixty-three patients were diagnosed with HRD during 1990 to 2019; 58 of them had an endocrine evaluation.
We investigated somatic growth parameters, the prevalence of hypoglycemia, growth hormone deficiency, hypothyroidism, hypogonadism, and cortisol deficiency.
All patients were born small for gestational age, and severe growth retardation was found in all patients with mean height standard deviation score (SDS) of -8.8 (range: -5.1 to -15.1) and weight SDS -18 (range: -5.1 to -61.2). Serum insulin-like growth factor-1 concentrations were very low among the 21 studied patients: -2.32 SDS (range: -0.6 to -2.7). Four out of 14 (28%) investigated patients had growth hormone deficiency, and 55% of patients were hospitalized due to symptomatic hypoglycemia. Adrenal glucocorticoid insufficiency was diagnosed in 22% of those tested. Hypothyroidism was found in 36% of patients. Both hypogonadotrophic and hypergonadotrophic hypogonadism were observed. The main magnetic resonance imaging findings were small anterior pituitary gland, small hippocampus, brain atrophy, thin corpus callosum, Chiari type I malformation, and septo-optic dysplasia.
Multiple endocrine abnormalities are common in patients with HRD syndrome. Periodic screening of thyroid and adrenal functions is recommended.
罕见的甲状旁腺功能减退-发育迟缓-畸形综合征（HRD，在线人类孟德尔遗传数据库编号#241410）由微管蛋白伴侣E（TBCE）基因突变引起。该基因在微管组装途径中编码一种关键蛋白。
评估HRD患者的内分泌特征。
本研究对一所大学医学中心的一大群患者进行回顾性分析。1990年至2019年期间，63例患者被诊断为HRD；其中58例接受了内分泌评估。
我们调查了身体生长参数、低血糖、生长激素缺乏、甲状腺功能减退、性腺功能减退和皮质醇缺乏的患病率。
所有患者出生时均为小于胎龄儿，所有患者均有严重生长迟缓，平均身高标准差评分（SDS）为-8.8（范围：-5.1至-15.1），体重SDS为-18（范围：-5.1至-61.2）。在21例研究患者中，血清胰岛素样生长因子-1浓度非常低：-2.32 SDS（范围：-0.6至-2.7）。14例接受调查的患者中有4例（28%）生长激素缺乏，55%的患者因症状性低血糖住院。22%的受检者被诊断为肾上腺糖皮质激素不足。36%的患者存在甲状腺功能减退。观察到低促性腺激素性和高促性腺激素性性腺功能减退。主要的磁共振成像表现为垂体前叶小、海马体小、脑萎缩、胼胝体薄、Chiari I型畸形和视隔发育不良。
HRD综合征患者常见多种内分泌异常。建议定期筛查甲状腺和肾上腺功能。
