ESPE Abstracts

Introduction: Barakat syndrome, also known as HDR syndrome (OMIM 146255), is a clinically heterogeneous, rare, autosomal dominant genetic disorder, characterized by the triad of hypoparathyroidism (H), deafness (D), and renal disease (R). The phenotypic features are attributed to mutations of the GATA3 gene, which encodes a transcription factor essential for embryonic development of the parathyroid glands, auditory system, and kidneys. Here, we report the case of a boy who presented with symptomatic hypocalcemia and was subsequently diagnosed with Barakat Syndrome.

Case: A 4.75 year-old male patient, who had a pre-existing diagnosis of Fanconi aplastic anemia, presented with generalized tonic-clonic, afebrile convulsions. The parents were first-degree cousins. Laboratory investigations showed: serum calcium 4.25 mg/dL (8.8-10.6); ionized calcium 0.55 mmol/L (1.15 - 1.29); phosphorus 12.2 mg/dL (3.8- 6.5); magnesium 2.5 mg/dL (1.6-2.6); alkaline phosphatase (ALP) 226 U/L (55-377); 25-hydroxy vitamin D (25OHD3) 20.0 ng/mL (20-100); and parathyroid hormone (PTH) <1.2 pg/mL (12-88) indicating hypoparathyroidism. He had normal renal functions on biochemical testing, but urinary system ultrasonography revealed a decrease in the size of the left kidney. He had bilateral sensorineural hearing loss, detected by audiometry. While his seizures were controlled with intravenous calcium gluconate and calcitriol treatment, serum calcium and phosphorus returned to normal. Fluorescence in situ hybridization studies excluded DiGeorge Syndrome as the etiology of his hypoparathyroidism. Next-generation sequencing of the patient, who was clinically considered to have Barakat Syndrome, revealed a c.480C>G (p.Asp160Glu) heterozygous, missense, variant of uncertain significance (VUS) in GATA3. Since no abnormality was found in his parents when examined for the components of Barakat Syndrome, the detected variant was thought to be de novo. The patient, who is in the first year of follow-up, is being treated with 30 ng/kg/day calcitriol and 50 mg/kg/day elemental calcium and has had a normocalcemic course.

Conclusion: Although Barakat syndrome is rare, it should be kept in mind in the differential diagnosis of hypoparathyroidism, and urinary system imaging, hearing evaluation and GATA3 gene analysis should be performed in suspected cases.