Barakat syndrome revisited

Barakat syndrome also known as HDR syndrome (Online Mendelian Inheritance in Man [OMIM] 146255), was first described by Barakat et al. in 1977 . It is a rare genetic disorder characterized by the triad of hypoparathyroidism “H,” sensorineural deafness “D,” and renal disease “R.” The defect is caused by deletions in chromosome 10p14 or mutations in the GATA3 gene. Although the syndrome has been phenotypically defined by this triad the literature identifies cases with different components with, or without GATA3 defects making the definition of the syndrome confusing. We analyzed 180 cases and attempted to define the phenotype of the syndrome and suggest guidelines for diagnosis. We suggest that the diagnosis could be confirmed in patients who have all three components, and in those who have two components with a positive family history. GATA3 testing is optional to establish the diagnosis in these patients. The syndrome should be considered in patients with isolated “D” where other causes of “D” have been excluded and those with isolated “R,” especially if there is family history of any of these components. In these instances, confirmatory GATA3 testing is indicated to confirm the diagnosis. In patients with nonsurgical “H,” where “D” and “R” have been conclusively ruled out GATA3 studies are not needed as none of these patients were shown to be GATA3 haploinsufficient. Only 64.4% of patients in our review had “HDR.” Some findings might have not been recognized or may could have appeared later in life, but it is evident that this syndrome is genotypically heterogeneous.     

Familial disorders of parathyroid glands

The molecular mechanisms underlying familial parathyroid diseases continue to be elucidated. The mechanisms of familial parathyroid diseases are better understood than many sporadic parathyroid diseases. Familial parathyroid disease is associated with multiple endocrine neoplasia type 1 which is associated with MEN1 mutation, multiple endocrine neoplasia type 2A caused by RET mutation, and multiple endocrine neoplasia type 4 is caused with CDKN1B mutation. Sporadic parathyroid tumours are identified with mutations of MEN1 but generally not of RET. CDKN1B mutations are also identified in sporadic forms of primary hyperparathyroidism, although very rarely. Calcium sensing receptor gene mutations are involved in familial hyperparathyroidism and hypoparathyroidism, but are generally not identified in sporadic parathyroid tumours. However, the HPRT2 (CDC73) gene, which is mutated in hyperparathyroidism jaw-tumour syndrome and a subset of cases of familial isolated hyperparathyroidism, is frequently mutated in sporadic parathyroid carcinomas. Germline activating GCM2 mutations were recently found associated with a subset of familial isolated hyperparathyroidism. Parafibromin, a protein encoded by HPRT2, has been used in the diagnostic setting. The understanding and pathogenesis of parathyroid disease continues to evolve.     

特发性甲状旁腺功能减退症25例临床分析

目的探讨特发性甲状旁腺功能减退症（IHP）的临床特点、诊断及治疗。方法对华西医院内分泌科收治的IHP病例25例进行回顾性分析。结果本组IHP患者的常见症状为：手足抽搐发生率为84%,癫痫发生率为32%,肢端麻木发生率为44%,乏力发生率为44%,晕厥发生率为16%,锥体外系症状为16%。20例行头颅CT检查,75%（15例）发现颅内钙化。误诊率为44%。主要误诊为：原发性癫痫、缺钙、肌炎、风湿。结论本病临床表现复杂,易被误诊。为减少误诊,临床医生应警惕低钙血症的临床表现。长期治疗包括钙剂和维生素D或其衍生物。