Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目标：甲状旁腺功能减退，耳聋,和肾发育不良（HDR）综合征，也被称为巴拉卡特综合征，是一种罕见的常染色体显性疾病，其特征是甲状旁腺功能减退三联症，耳聋,和肾脏异常。该疾病是由锌指转录因子GATA3的单倍体不足引起的，并且表现出很大的临床变异性，每个特征都具有年龄依赖性。我们报告了两个无关的家族，他们的先证者被转诊到我们的门诊，以进一步评估甲状旁腺功能减退症。
方法：家庭1的先证者，一个17岁的男孩，在常规血液检查中偶然发现严重的低钙血症（5.9mg/dL）。腹部超声显示双侧肾囊肿。听力测量评估显示存在双侧中度听力损失，尽管患者可以毫无问题地进行交流。相反，家庭2的先证者，一名19岁的男子，在14岁时患有严重的症状性低钙血症并伴有癫痫发作;由于在18岁时诊断出的多囊性肾病和双侧听力损失，他的既往病史在4个月大时进行了右肾切除术。
结果：基于临床，生物化学，和放射学数据，怀疑HDR综合征，对GATA3基因的遗传分析显示，外显子3中存在两个致病变异，c.404dupC和c.431dupG，分别在家庭1和2的先证者中。
结论：HDR综合征是甲状旁腺功能减退症的罕见原因，在所有明显特发性甲状旁腺功能减退症患者中必须排除。正确的诊断对于早期发现其他HDR相关特征和遗传咨询非常重要。
方法：家庭1的先证者，一个17岁的男孩，在常规血液检查中偶然发现严重的低钙血症（5.9mg/dL）。腹部超声显示双侧肾囊肿。听力测量评估显示存在双侧中度听力损失，尽管患者可以毫无问题地进行交流。相反，家庭2的先证者，一名19岁的男子，在14岁时患有严重的症状性低钙血症并伴有癫痫发作;由于在18岁时诊断出的多囊性肾病和双侧听力损失，他的既往病史在4个月大时进行了右肾切除术。
结果：基于临床，生物化学，和放射学数据，怀疑HDR综合征，对GATA3基因的遗传分析显示，外显子3中存在两个致病变异，c.404dupC和c.431dupG，分别在家庭1和2的先证者中。
结论：HDR综合征是甲状旁腺功能减退症的罕见原因，在所有明显特发性甲状旁腺功能减退症患者中必须排除。正确的诊断对于早期发现其他HDR相关特征和遗传咨询非常重要。
