Category: Calcium/Bone Disorders

Monitor: 3

3 - Autosomal Dominant Hypocalcemia: A Novel Activating Mutation NM_000388.3(CASR):c.825 T>A p.(Asp 275 Glu) in the Calcium-Sensing Receptor gene

Thursday, Apr 25
11:00 AM – 11:30 AM

Objective : Autosomal dominant hypocalcemia ( ADH) , caused by activating mutations of the calcium- sensing receptor (CASR) gene, is characterised by hypocalcemia with an inappropriately  low concentration of parathyroid hormone (PTH). In this report, we describe the identification of a novel activating  mutation in CASR gene, c.825T>A p.(Asp 275 Glu)  in the calcium sensing receptor in a family with autosomal dominant hypocalcemia with index case found to be heterozygous for above mentioned  mutant gene. No functional analysis was performed  but in silico analysis this could be activating mutation in which aspartic acid  was substituted for glutamic acid at codon 275.


Methods : n/a


Results :

The  affected individual is a 50 yr- old caucasian lady with Spanish ancestry without  history of consanguinity ..She exhibited mild to moderate  hypocalcemia with inappropriately  low PTH . Laboratory analysis also  revealed  hyperphosphatemia, low-serum PTH, hypomagnesemia , mild hypercalciuria and mild normocytic normochromic anemia  .She did have paresthesia  but no personal or family history of seizure was present. Her management was complicated by renal dysfunction as soon as we tried to correct calcium to low normal level . Her BMD of hip and spine was consistent with excess osteogenesis . Her renal dysfunction was causing anemia and typically responded to withdrawal of treatment and a short course of erythropoietin. After 3 years of treatment with calcium supplements and calcitriol, she had  clinical improvement were reported; as well as an absence of nephrocalcinosis. 


Discussion :

ADH is hard to be distinguish from isolated primary hypoparathyroidism on the basis of measurements of serum PTH and urinary calcium. These patients are often labeled as having idiopathic hypoparathyroidism,  and  we   need to perform a  mutational analysis of CASR gene  to differentiate it from primary hypoparathyroidism.  Hence ,a screening for mutations in the CASR gene is an important step in the work- up of this endocrine disorder, especially in hypocalcemic patients with relatively high urinary calcium excretion or in the evaluation of children with isolated hypoparathyroidism without a clear mode of inheritance in which the finding of a de novo CASR mutation can exclude others causes. 


Conclusion : This case demonstates the importance of  assesing the renal function  and hemoglobin while trying to correct  hypocalemia . It also showed variable phenotypic expression in family memebers with hypocalcemia . A novel mutation added to the list of already known mutations may  help in understanding of autosomal dominant hypocalcemia further  .

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Santosh K. Chaubey

SENIOR CONSULTANT ENDOCRINOLOGIST
Sahara Hospital , Lucknow
Dist: Mahrajgnaj, Uttar Pradesh, India

I completed my graduation i.e. MBBS and postgraduate course i.e. MD ( Internal Medicine) from King George's Medical University, Lucknow, UP and moved to Australia in 2004 for higher qualifications. I started my basic physician training accredited by Royal Australasian College of Physicians ( adult medicine division) in 2005 and after passing written and clinical examinations , I was selected for advanced training in Endocrinology by RACP in 2008. After successful completion of 3 years of advanced training in Endocrinology ,I was awarded a degree of Fellow of The Royal Australasian College of Physicians (FRACP) in Endocrinology in 2010. I received training in 6 large tertiary level hospitals in Vic and Queensland states. Subsequently, I worked as Consultant Endocrinologist in Cairns Hospital, Cairns Private Hospital, Cairns QLD, Gosford Hospital, Gosford, NSW and Gosford Pvt. Hospital, Gosford, NSW, Australia. I moved back to India and started working as consultant Endocrinologist and Diabetologist in Sahara Hospital , Lucknow in Feb 2016 and also runs a endocrine and diabetes clinic in Gomti Nagar, Lucknow, India.

Kunwarjit Sangla

SENIOR CONSULTANT ENDOCRINOLOGIST
THE TOWNSVEILLE HOSPITAL , TOWSNVILLE, QLD
Townsville, Queensland, Australia

Dr. Kunwarjit Singh Sangla is a Specialist endocrinologist practicing at Townsville Hospital in Douglas and Maters Hospital in Pimlico. He also has academic affiliation with James Cook University , Townsville , Qld as Associate Professor of Medicine .

Santosh K. Chaubey

SENIOR CONSULTANT ENDOCRINOLOGIST
Sahara Hospital , Lucknow
Dist: Mahrajgnaj, Uttar Pradesh, India

I completed my graduation i.e. MBBS and postgraduate course i.e. MD ( Internal Medicine) from King George's Medical University, Lucknow, UP and moved to Australia in 2004 for higher qualifications. I started my basic physician training accredited by Royal Australasian College of Physicians ( adult medicine division) in 2005 and after passing written and clinical examinations , I was selected for advanced training in Endocrinology by RACP in 2008. After successful completion of 3 years of advanced training in Endocrinology ,I was awarded a degree of Fellow of The Royal Australasian College of Physicians (FRACP) in Endocrinology in 2010. I received training in 6 large tertiary level hospitals in Vic and Queensland states. Subsequently, I worked as Consultant Endocrinologist in Cairns Hospital, Cairns Private Hospital, Cairns QLD, Gosford Hospital, Gosford, NSW and Gosford Pvt. Hospital, Gosford, NSW, Australia. I moved back to India and started working as consultant Endocrinologist and Diabetologist in Sahara Hospital , Lucknow in Feb 2016 and also runs a endocrine and diabetes clinic in Gomti Nagar, Lucknow, India.