Endocrine Abstracts

Case history: A 54-year-old lady was diagnosed with primary hypoparathyroidism in 2006, after being referred by her Rheumatologist as her father and brother had familial hypoparathyroidism and sensorineural deafness. She was followed up in endocrine clinic for management of primary hypoparathyroidism. Her hypocalcaemia is well managed with calcium supplementation, with no specific symptoms of hypocalcaemia. She has recurrent urinary tract infections with known borderline chronic kidney disease. Other notable past medical history includes familial sensorineural deafness from childhood and psoriatic arthritis with enthesitis. After discussion on an internet hypoparathyroidism support group in 2015, she questioned the possibility of her having “Barakat syndrome”.

Investigations: In 2005, adjusted calcium level was 2.12 (normal range 2.2-2.6 nmol/l) and PTH level was 21 (normal 7-53 range pg/ml). With treatment, adjusted calcium and phosphate levels remain within normal limits. Known chronic mild anaemia. Twenty-four-hour urinary calcium output performed in February 2022 was < 2.548 mmol/24h (2.7-7.5 mmol/24hr) in 3185ml urine. Urea 5.7 (normal range 3-7.6 mmol/l), creatinine 99 (normal range 55-87 mmol/l) and eGFR 56 ml/min. Sequencing GATA3 analysis for this patient in 2015 showed heterozygous mutations of c.291 303delins6p(Asp98fs). An MRI brain in 2019 was negative for basal ganglia calcification, excluding Fahr”s syndrome. Renal USS 2020 showed slightly atrophic right kidney measuring 8.5 cm, normal left kidney. Microalbuminuria was confirmed in 2021, with urinary microalbumin of 140mg/l (normal range < 30mg/l).

Management: Barakat syndrome was diagnosed in this patient due to the classical triad of diagnoses, confirmed by genetic analysis showing heterozygous GATA3 mutation. Her hypocalcaemia is well managed with 250nanograms 1-alfacalcidiol three times daily. Her seronegative arthritis is managed with analgesia and anti-rheumatic agents. Her chronic anaemia is managed by iron and blood transfusions as required.

Conclusions and discussion: Barakat syndrome is an autosomal dominant genetic disorder caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene. There are currently no formal guidelines for diagnosis. In this case, the patient presented with classical triad of renal disease, sensorineural deafness, and hypoparathyroidism, with diagnosis being confirmed via genetic analysis. From those with Barakat syndrome confirmed on genetic testing, 60% have all three classical manifestations, with 27% not having renal disease. The most common individual phenotypic presentation was deafness (93%), then hypoparathyroidism (87%), with least common being renal disease (61%). Therefore, Barakat syndrome should be considered in those presenting with any of sensorineural deafness, hypoparathyroidism or renal disease. Genetic testing could be used as a means for earlier diagnosis.