title: Phenotypic variation in a large family with autosomal dominant hypocalcaemia.
abstract: OBJECTIVE
  Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium- sensing receptor (CASR). We aimed to describe the phenotypic variation within a large family with ADH, especially kidney and cerebral basal ganglia calcifications.
  
  
  METHODS
  Fifteen related subjects carrying the CASR mutation T151M participated in a cross-sectional study of calcium homeostasis, renal ultrasonography, cerebral CT, bone mineral density, and health-related quality of life (HRQoL).
  
  
  RESULTS
  Eight subjects had received vitamin D treatment (mean duration 15.3 years; range 11-20 years). Urinary calcium excretion was elevated in 5/8 vitamin-D-treated and in 3/7 untreated subjects. Serum magnesium, calcium and parathyroid hormone remained at the lower reference limit or below. Renal calcifications were found in 12 of 14 (86%) and basal ganglia calcifications in 5 of 11 (46%) subjects, independently of vitamin D therapy. The glomerular filtration rate was moderately reduced in 3 subjects. Mean bone mineral density and bone markers were normal. HRQoL was impaired in the vitamin-D-treated group despite correction of the hypocalcaemia.
  
  
  CONCLUSIONS
  The impact of the CASR mutation on calcium homeostasis varied greatly. Kidney and basal ganglia calcifications are common in ADH independently of vitamin D treatment, which, however, increases urinary calcium excretion and may promote urolithiasis.
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway. Jan.Inge.Sorheim @ helse-bergen.no
authors.forename: J I
authors.initials: JI
authors.lastname: Sørheim
authors.forename: E S
authors.initials: ES
authors.lastname: Husebye
authors.forename: B G
authors.initials: BG
authors.lastname: Nedrebø
authors.forename: E
authors.initials: E
authors.lastname: Svarstad
authors.forename: J
authors.initials: J
authors.lastname: Lind
authors.forename: H
authors.initials: H
authors.lastname: Boman
authors.forename: K
authors.initials: K
authors.lastname: Løvås
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015519:Bone Density / Q000235:genetics; D002114:Calcinosis / Q000235:genetics; D002118:Calcium / Q000378:metabolism / Q000652:urine; D054022:Cerebrum / Q000378:metabolism / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010281:Parathyroid Hormone / Q000097:blood; D010375:Pedigree; D010641:Phenotype; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D002118:Calcium