A family with autosomal dominant hypocalcaemia with hypercalciuria (ADHH): Mutational analysis, phenotypic variability and treatment challenges

Christine P. Burren*, A. Curley, P. Christie, C. P. Rodda, R. V. Thakker

*Corresponding author for this work

    Research output: Contribution to journalArticle (Academic Journal)peer-review

    16 Citations (Scopus)

    Abstract

    Autosomal dominant hypocalcaemia with hypercalciuria (ADHH) is an intriguing syndrome, in which activating mutations of the calcium sensing receptor (CaSR) have recently been recognised. We describe a kindred with seven affected individuals across three generations, including patients affected in the first decade of life. Age at diagnosis varied from birth to 50 years. Affected members had hypocalcaemia (1.53-1.85 mmol/l), hypercalciuria, low but detectable parathyroid hormone (PTH) and hypomagnesaemia. Four of seven affected individuals were symptomatic (seizures, abdominal pains and paraesthesias), unrelated to severity of hypocalcaemia. Additional complications include nephrocalcinosis (n = 3) and basal ganglia calcification, identified by CT scanning in all five individuals. Symptomatic individuals were treated with calcium and calcitriol to reduce the risk of hypocalcaemic seizures. DNA sequence analysis, identified a mutation in exon 3, codon 129 (TGC→TAC) of the CaSR gene of seven affected family members, resulting in loss of a conserved, cysteine residue, potentially disrupting CaSR receptor dimerisation. Thus, a novel mutation was identified in this family, who demonstrate variability of ADHH phenotype and also illustrate the complexities of clinical management. Optimal management of ADHH is difficult and we recommend judicious treatment to avoid an increased risk of nephrocalcinosis.

    Original languageEnglish
    Pages (from-to)689-699
    Number of pages11
    JournalJournal of Pediatric Endocrinology and Metabolism
    Volume18
    Issue number7
    DOIs
    Publication statusPublished - Jul 2005

    Bibliographical note

    Copyright:
    Copyright 2018 Elsevier B.V., All rights reserved.

    Keywords

    • ADHH
    • Hypercalciuria
    • Hypocalcaemia

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