Autosomal dominant hypocalcemia with a novel CASR mutation: a case study and literature review

Abstract

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare inherited disorder characterized by hypocalcemia with low parathyroid hormone (PTH) levels and high urinary calcium. Its clinical presentation varies from mild asymptomatic to severe hypocalcemia. It is caused by gain-of-function mutations in the calcium-sensing receptor gene (CASR) which affect PTH secretion from the parathyroid gland and calcium resorption in the kidney. Here, we describe a case who presented with symptoms of recurrent seizure caused by hypocalcemia with a novel CASR variant. We comprehensively analyzed the phenotypic features of this presentation and reviewed the current literature to better understand clinical manifestations and the genetic spectrum.

Keywords: Autosomal dominant hypocalcemia type 1; CASR; calcification; hyperphospheremia; hypoparathyroidism; seizure.

Figure 1.

(a) Family pedigree. (b) Brain CT showing multiple calcifications in the bilateral frontal lobe, parietal lobe, temporal lobe, occipital lobe, basal ganglia, and cerebellum. (c) Sanger sequencing showing a CASR heterozygous mutation (c.416T > C) in the proband, and wild-type sequence in his parents and (d) Conservation of the 139th amino acid among different species.