Dinoi E, Pierotti L, Mazoni L, Citro F, Della Valentina S, Sardella C, Borsari S, Michelucci A, Caligo M A, Marcocci C, Cetani F
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Endocrine Unit 2, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
J Endocrinol Invest. 2024 Feb;47(2):469-478. doi: 10.1007/s40618-023-02171-8. Epub 2023 Aug 10.
Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant disease characterized by the triad of hypoparathyroidism, deafness, and renal abnormalities. The disorder is caused by the haploinsufficiency of the zinc finger transcription factor GATA3 and exhibits a great clinical variability with an age-dependent penetrance of each feature. We report two unrelated kindreds whose probands were referred to our outpatient clinic for further evaluation of hypoparathyroidism.
The proband of family 1, a 17-year-old boy, was referred for severe hypocalcemia (5.9 mg/dL) incidentally detected at routine blood tests. Abdomen ultrasound showed bilateral renal cysts. The audiometric evaluation revealed the presence of bilateral moderate hearing loss although the patient could communicate without any problem. Conversely, the proband of family 2, a 19-year-old man, had severe symptomatic hypocalcemia complicated by epileptic seizure at the age of 14 years; his past medical history was remarkable for right nephrectomy at the age of 4 months due to multicystic renal disease and bilateral hearing loss diagnosed at the age of 18 years.
Based on clinical, biochemical, and radiologic data, HDR syndrome was suspected and genetic analysis of the GATA3 gene revealed the presence of two pathogenetic variants in exon 3, c.404dupC and c.431dupG, in the proband of family 1 and 2, respectively.
HDR syndrome is a rare cause of hypoparathyroidism and must be excluded in all patients with apparently idiopathic hypoparathyroidism. A correct diagnosis is of great importance for early detection of other HDR-related features and genetic counseling.
甲状旁腺功能减退、耳聋和肾发育不良（HDR）综合征，也称为巴拉卡特综合征，是一种罕见的常染色体显性疾病，其特征为甲状旁腺功能减退、耳聋和肾脏异常三联征。该疾病由锌指转录因子GATA3单倍剂量不足引起，且各特征的发病具有年龄依赖性，临床表现差异很大。我们报告了两个无血缘关系的家系，其先证者因甲状旁腺功能减退被转诊至我们的门诊进行进一步评估。
家系1的先证者是一名17岁男孩，因常规血液检查偶然发现严重低钙血症（5.9mg/dL）而被转诊。腹部超声显示双侧肾囊肿。听力评估显示存在双侧中度听力损失，不过患者沟通没有任何问题。相反，家系2的先证者是一名19岁男性，14岁时出现严重的症状性低钙血症并伴有癫痫发作；他既往病史中值得注意的是，因多囊肾病在4个月大时进行了右肾切除术，18岁时被诊断为双侧听力损失。
根据临床、生化和放射学数据，怀疑为先证者患有HDR综合征，对GATA3基因进行遗传分析后发现，家系1和家系2的先证者分别在外显子3中存在两个致病变异，即c.404dupC和c.431dupG。
HDR综合征是甲状旁腺功能减退的罕见病因，所有明显特发性甲状旁腺功能减退的患者均须排除该病因。正确诊断对于早期发现其他HDR相关特征和遗传咨询非常重要。
