title: Muscle function and quality of life are not impaired in familial hypocalciuric hypercalcemia: a cross-sectional study on physiological effects of inactivating variants in the calcium-sensing receptor gene (CASR).
abstract: BACKGROUND
  Familial hypocalciuric hypercalcemia (FHH) is often due to inactivating variants in the calcium-sensing receptor (CASR) gene causing chronically elevated plasma calcium levels with inappropriately normal or elevated parathyroid hormone levels. In patients with primary hyperparathyroidism, the state of hyperparathyroid hypercalcemia is associated with reduced muscle strength and impaired quality of life (QoL).
  
  
  OBJECTIVE
  To study whether FHH affects muscle function, postural stability, and QoL.
  
  
  METHODS
  In a cross-sectional study, we investigated muscle strength (handgrip, elbow flexion/extension, and knee flexion/extension), balance function, physical activity, and QoL in 50 patients with FHH and in a similar number of age- and gender-matched population-based healthy controls. All but one of the FHH cases had genetically verified inactivating variants in the CASR gene.
  
  
  RESULTS
  Studied subjects (n=100, 68% females) had a mean age of 56.0 years. Muscle strength as assessed by measuring maximum force and maximum force production did not differ between the groups. Neither did groups differ in terms of QoL, physical activity, or postural stability, as assessed during normal standing with eyes open, normal standing with eyes closed, semi-tandem standing, or tandem standing. Adjustment for vitamin D status (plasma 25-hydroxyvitamin D levels) and BMI did not change results.
  
  
  CONCLUSIONS
  Despite a state of chronic hypercalcemia, muscle strength, balance function, and QoL are not impaired in patients with FHH. Our findings are reassuring for patients with FHH as they should not be considered as having a severe disease.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark. fbjakobsen@gmail.com
authors.forename: Niels Frederik Breum
authors.initials: NF
authors.lastname: Jakobsen
authors.forename: Lars
authors.initials: L
authors.lastname: Rolighed
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nissen
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
authors.forename: Lars
authors.initials: L
authors.lastname: Rejnmark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D003718:Denmark; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D053580:Muscle Strength; D009132:Muscles / Q000503:physiopathology*; D009135:Muscular Diseases / Q000209:etiology* / Q000503:physiopathology; D009154:Mutation; D004856:Postural Balance; D011788:Quality of Life; D044169:Receptors, Calcium-Sensing / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing