Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2022) 81 EP177 | DOI: 10.1530/endoabs.81.EP177

ECE2022 Eposter Presentations Calcium and Bone (114 abstracts)

Identification of GATA3 pathogenic variants in two patients with hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome

Elisa Dinoi 1 , Laura Pierotti 1 , Laura Mazoni 1 , Simona Borsari 1 , Matteo Apicella 1 , Fulvia Baldinotti 2 , Maria Adelaide Caligo 2 , Claudio Marcocci 1 & Filomena Cetani 3

1University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy; 2University Hospital of Pisa, Laboratory of Molecular Genetics, Pisa, Italy; 3University of Pisa, Endocrine 2 Unit, Pisa, Italy.

Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant disease characterized by the triad of hypoparathyroidism (H), deafness (D) and renal abnormalities (R). Its genetic cause is known to be the haploinsufficiency of the zinc finger transcription factor GATA3. This disorder exhibits a great clinical variability and an age-dependent penetrance of each feature. The most frequent manifestation is sensorineural deafness, usually diagnosed during childhood. Symptomatic or asymptomatic hypoparathyroidism affects about 90% of patients. Kidney abnormalities, such as renal cysts, are less common. We report two cases of HDR syndrome due to pathogenic variants in exon 3 of the GATA3 gene. Subject 1 was a 17-years-old boy who was referred to our Department in 2018 for hypocalcemia incidentally detected at routine blood tests. At physical examination Trousseau and Chvostek signs were positive and laboratory evaluation confirmed a severe hypocalcemia (ionized calcium 0.62 mmol/l, n.v. 1.13–1.32), hyperphosphatemia (8.8 mg/dl) with undetectable PTH levels (< 4 pg/ml, n.v. 8–40). At abdomen ultrasound and magnetic resonance multiple renal cysts were detected. Subject 2 was a 16-years-old boy who was referred to our Department in 2005 for hypocalcemia complicated by epileptic seizure. His past clinical history was remarkable for right nephrectomy at 4 months of age for multicystic renal disease. At our first evaluation physical examination was normal and blood tests showed low ionized calcium (0.99 mmol/l, n.v. 1.13–1.32) with undetectable PTH levels (< 10 pg/ml, n.v. 15–75). Computed tomography displayed multiple cerebral calcifications and the audiometric evaluation revealed the presence of bilateral mild sensorineural hearing loss in both patients. On the basis of clinical and biochemical data, HDR syndrome was suspected and genetic analysis of the GATA3 gene revealed the presence of a pathogenetic variant in exon 3, c.404dupC in subject 1, but not in his parents and sister, and c.431dupG in subject 2. These frameshift variants produce a premature stop codon resulting in the synthesis of a non-functional truncated protein (p.Ala136GlyfsTer168 and p.His145ProfsTer159, respectively). A good control of H is achieved in both patient by using rhPTH in subject 1 and oral calcium and active vitamin D in subject 2. HDR syndrome, although rare, is one of the genetic causes of H and must be excluded in all patients with idiophatic H, particularly if young. A correct diagnosis is important for the early detection of other features of the syndrome and for genetic counseling.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

Browse other volumes

Article tools

My recent searches

No recent searches.