A rare cause of hypocalcemia: Hypoparathyroidism, sensorineural deafness, and renal disease syndrome :Sufyan Benamer, Paul Jennings, Libyan Journal of Medical Sciences

CASE REPORT
Year : 2020 | Volume : 4 | Issue : 4 | Page : 196--197

A rare cause of hypocalcemia: Hypoparathyroidism, sensorineural deafness, and renal disease syndrome

Sufyan Benamer¹, Paul Jennings²,
¹ Diabetes and Endocrinology Consultant, York Hospital, York, UK
² Diabetes and Endocrinology Centre, York Hospital, York, UK

Correspondence Address:
Dr. Sufyan Benamer
Diabetes and endocrinology centre, York Hospital, Wigginton Road, YO31 8HE
UK

Abstract

Hypocalcemia is a common electrolyte disturbance with a variety of causes. Hypoparathyroidism, sensorineural deafness, and renal disease (HDR) syndrome is a rare autosomal-dominant genetic disorder characterized by hypoparathyroidism, sensorineural deafness, and renal disease. This is a case presentation of HDR syndrome that had been referred to a hospital with hypocalcemia. This case has a unique feature as it has been diagnosed in adult age because usually HDR syndrome is diagnosed in pediatric age group.

How to cite this article:
Benamer S, Jennings P. A rare cause of hypocalcemia: Hypoparathyroidism, sensorineural deafness, and renal disease syndrome.Libyan J Med Sci 2020;4:196-197

How to cite this URL:
Benamer S, Jennings P. A rare cause of hypocalcemia: Hypoparathyroidism, sensorineural deafness, and renal disease syndrome. Libyan J Med Sci [serial online] 2020 [cited 2023 Mar 28 ];4:196-197
Available from: https://www.ljmsonline.com/text.asp?2020/4/4/196/305247

Full Text

Introduction

Hypocalcemia is a common presentation to acute medical departments, ambulatory care units, and endocrinology services. Calcium concentration is influenced by parathyroid hormone (PTH), Vitamin D, calcium ions, and phosphate.[1] Hypocalcemia is often caused by disorders in PTH or Vitamin D. Low calcium level with low PTH could be due to destruction of the parathyroid gland (postsurgery or autoimmune), altered development of parathyroid gland, or abnormal regulation of PTH production or secretion. Postsurgical hypocalcemia is the most common cause. Hypocalcemia, sensorineural deafness, and renal disease (HDR syndrome) is a rare, genetic syndrome characterized by hypoparathyroidism, sensorineural deafness, and renal disease.[2],[3] Mutations in GATA-binding protein 3 (GATA3), a gene localized to the chromosome region 10p14-15, have been detected in families affected by the syndrome. GATA3 is involved in the development of PTH, kidneys and inner ear, thymus, and central nervous system.[4],[5]

Case Report

A 30-year-old female patient was referred to the hospital with symptoms of generalized fatigue, mouth numbness, and tingling. Her past medical history included bilateral sensorineural deafness with hearing aids since childhood. In addition, she had inborn unilateral renal agenesis. There was no previous history of calcium metabolism disorder with any history of previous hospital admission. Her father had bilateral sensorineural deafness.

Biochemical evaluation showed low adjusted calcium level at 1.85 mmol/L (normal level 2.2–2.6 mmol/L), high phosphate level at 1.7 mmol/L (normal value 0.8–1.5 mmol/L), low PTH level at 1.2 pmol/L (normal level 1.6–6.9 pmol/L), normal Vitamin D at 55 nmol/L (normal level 40–60 pmol/L), normal magnesium at 1 mmol/L (normal level at 0.85–1.1 mmol/L), and mild renal impairment with urea at 8 mmol/L and creatinine at 110 μmol/L (normal urea 2.5–7 mmol/L and normal creatinine 60–100 μmol/L) [Table 1]. Her ultrasound showed right renal agenesis. There were no electrocardiogram changes.{Table 1}

Based on her clinical presentation with hypocalcemia, sensorineural deafness, and renal impairment, HDR syndrome was suspected and genetic analysis was undertaken which showed mutations in GATA3, which confirmed HDR syndrome.

She was treated with calcium supplement, alfacalcidol, and is under regular follow-up with endocrinology services. This is an uncommon presentation of HDR syndrome as it usually presents at younger age group.

Discussion

Hypoparathyroidism “H,” sensorineural deafness “D,” and renal disease “R” (HDR syndrome), also known as Barakat syndrome, is an autosomal-dominant disorder caused by germline inactivating mutations of the GATA3 gene.[1],[2] GATA3 encodes a transcription factor that is involved in embryonic development of the parathyroid glands, inner ear, and kidneys.[2],[3],[4] HDR syndrome has a wide phenotypic variability. The triad of HDR syndrome is found in 64.5% of patients.[6] The diagnosis of HDR syndrome could be confirmed in patients who have the triad of HDR syndrome or two of the three factors of HDR syndrome with a positive family history.[6] In patients with isolated nonsurgical hypoparathyroidism, “H,” “D,” and “R” are not found, and hence HDR syndrome is not considered in the diagnosis.[6]

Hypoparathyroidism has a variable age of onset and is characterized by asymptomatic or symptomatic presentation; this could range from mild symptoms of tingling and numbness to tetany and convulsion.[7],[8] The majority of patients have symmetrical sensorineural deafness and could range from mild to profound in severity.[7],[8] Renal anomalies in HDR syndrome are also heterogeneous and include renal dysplasia, hypoplasia, or aplasia, nephritis syndrome, cystic disease, and vesicoureteric reflux.[9]

HDR syndrome is a rare autosomal genetic disorder with variable age presentation.[10] Our patient had the full triad of HDR syndrome with peculiar late age of diagnosis, compared to that of other reported HDR cases.[11]

Conclusion

Diagnosis of HDR syndrome is still challenging, but clinicians should consider it in their differential diagnosis with a wide range of clinical manifestations including hypocalcemia, renal abnormalities, and deafness.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1	Riccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol 2010;298:F485-99.
2	Bilous RW, Murty G, Parkinson DB, Thakker RV, Coulthard MG, Burn J, et al. Brief report: Autosomal dominant familial hypoparathyroidism, sensorineural deafness, and renal dysplasia. N Engl J Med 1992;327:1069-74.
3	Hasegawa T, Hasegawa Y, Aso T, Koto S, Nagai T, Tsuchiya Y, et al. HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia) associated with del(10)(p13). Am J Med Genet 1997;73:416-8.
4	van Esch H, Groenen P, Nesbit MA, Schuffenhauer S, Lichtner P, Vanderlinden G, et al. GATA3 haplo-insufficiency causes human HDR syndrome. Nature 2000;406:419-22.
5	Muroya K, Hasegawa T, Ito Y, Nagai T, Isotani H, Iwata Y, et al. GATA3 abnormalities and the phenotypic spectrum of HDR syndrome. J Med Genet 2001;38:374-80.
6	Barakat AJ, Raygada M, Rennert OM. Barakat syndrome revisited. Am J Med Genet A. 2018;176:1341-1348. doi: 10.1002/ajmg.a.38693. Epub 2018 Apr 16.
7	Sau T, Chatterjee A, Ghosh K, Dey S. Seizure, deafness and renal agenesis: A rare case of Barakat syndrome. Ann Indian Acad Neurol 2013;16:91-3.
8	Ranjbar-Omrani G, Zamiri N, Sabayan B, Mohammadzadeh A. Concomitant hypoparathyroidism, sensorineural deafness, and renal agenesis: A case of Barakat syndrome. Arch Iran Med 2008;11:337-40.
9	Maleki N, Bashardoust B, Almadri MI, Tavosi Z. Seizures, deafness, and renal failure: A case of Barakat Syndrome. Case Rep Nephrol 2013;2013:1-4.
10	Joseph AD, Sirisena ND, Kumanan T, Kumanan T, Sujanitha V, Strelow V, et al. Hypoparathyroidism, Sensorineural deafness and renal disease (Barakat syndrome) caused by a reduced gene dosage in GATA3: A case report and review of literature. BMC Endocr Disord 2019;19:111.
11	Ali A, Christie PT, Grigorieva IV, Harding B, Van Esch H, Ahmed SF, et al. Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome: Insight into mechanisms of DNA binding by the GATA3 transcription factor. Hum Mol Genet 2007;16:265-75.