Importance of dietary calcium and vitamin D in the treatment of hypercalcaemia in Williams-Beuren syndrome
-
Abstract
Background: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by the deletion of 26–28 genes on chromosome 7. Fifteen percent of WBS patients present with hypercalcaemia during infancy, which is generally mild and resolves spontaneously before the age of 4 years. The mechanisms underlying the transient hypercalcaemia in WBS are poorly understood.
Case: We report a case of severe symptomatic hypercalcaemia in a patient with WBS, in which treatment with mild calcium restriction, hyperhydration and repeated bisphosphonate administration only resulted in short-lasting effects. Long-term lowering of serum calcium was only achieved after reducing calcium and vitamin D intake to the bare minimum.
Conclusions: This case illustrates the potential severity of hypercalcaemia in WBS, and demonstrates that both the cause as well as the solution of this problem may be found in the intestinal absorption of calcium. We hypothesise that the phenotypical resemblance between WBS and transient idiopathic infantile hypercalcaemia can be explained by similarities in the underlying genetic defect. Patients suffering from transient infantile hypercalcaemia were recently described to have mutations in CYP24A1, the key enzyme in 1,25-dihydroxyvitamin D3 degradation. In the light of this new development we discuss the role of one of the deleted genes in WBS, Williams syndrome transcription factor (WSTF), in the etiology of hypercalcaemia in WBS.
References
1. Pober BR. Williams-Beuren syndrome. N Engl J Med 2010;362:239–52.10.1056/NEJMra0903074Search in Google Scholar
2. Barr DG, Forfar JO. Oral calcium-loading test in infancy, with particular reference to idiopathic hypercalcaemia. Br Med J 1969;1:477–80.10.1136/bmj.1.5642.477Search in Google Scholar
3. Kruse K, Pankau R, Gosch A, Wohlfahrt K. Calcium metabolism in Williams-Beuren syndrome. J Pediatr 1992;121:902–7.10.1016/S0022-3476(05)80336-1Search in Google Scholar
4. Martin ND, Snodgrass GJ, Cohen RD. Idiopathic infantile hypercalcaemia—a continuing enigma. Arch Dis Child 1984;59:605–13.10.1136/adc.59.7.605Search in Google Scholar PubMed PubMed Central
5. Gut J, Kutilek S. Idiopathic infantile hypercalcaemia in 5-month-old girl. Prague Med Rep 2011;112:124–31.Search in Google Scholar
6. Lameris AL, Huybers S, Burke JR, Monnens LA, Bindels RJ, Hoenderop JG. Involvement of claudin 3 and claudin 4 in idiopathic infantile hypercalcaemia: a novel hypothesis? Nephrol Dial Transplant 2010;25:3504–9.10.1093/ndt/gfq221Search in Google Scholar PubMed
7. Letavernier E, Rodenas A, Guerrot D, Haymann JP. Williams-Beuren syndrome hypercalcemia: is TRPC3 a novel mediator in calcium homeostasis? Pediatrics 2012;129:e1626–30.10.1542/peds.2011-2507Search in Google Scholar PubMed
8. Dauber A, Nguyen TT, Sochett E, Cole DE, Horst R, et al. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. J Clin Endocrinol Metab 2012;97:E268–74.10.1210/jc.2011-1972Search in Google Scholar PubMed PubMed Central
9. Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 2011;365:410–21.10.1056/NEJMoa1103864Search in Google Scholar PubMed
10. Tebben PJ, Milliner DS, Horst RL, Harris PC, Singh RJ, et al. Hypercalcemia, hypercalciuria, and elevated calcitriol concentrations with autosomal dominant transmission due to CYP24A1 mutations: effects of ketoconazole therapy. J Clin Endocrinol Metab 2012;97:E423–7.10.1210/jc.2011-1935Search in Google Scholar PubMed PubMed Central
11. Barnett C, Krebs JE. WSTF does it all: a multifunctional protein in transcription, repair, and replication. Biochem Cell Biol 2011;89:12–23.10.1139/O10-114Search in Google Scholar PubMed PubMed Central
12. Yoshimura K, Kitagawa H, Fujiki R, Tanabe M, Takezawa S, et al. Distinct function of 2 chromatin remodeling complexes that share a common subunit, Williams syndrome transcription factor (WSTF). Proc Natl Acad Sci USA 2009;106:9280–5.10.1073/pnas.0901184106Search in Google Scholar PubMed PubMed Central
13. St-Arnaud R, Arabian A, Travers R, Barletta F, Raval-Pandya M, et al. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology 2000;141:2658–66.10.1210/endo.141.7.7579Search in Google Scholar PubMed
©2014 by Walter de Gruyter Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Welcome to Assistant Editors at JPEM
- Review article
- Common approach to childhood obesity in Japan
- Images in pediatric endocrinology
- Aromatase deficiency in an adolescent girl misdiagnosed as congenital adrenal hyperplasia in infancy and childhood
- Original articles
- Prevalence of vitamin D deficiency among Iranian adolescents
- Analysis of body composition among children and adolescents – a cross-sectional study of the Polish population and comparison of body fat measurement methods
- Association of rs8066560 variant in the sterol regulatory element-binding protein 1 (SREBP-1) and miR-33b genes with hyperglycemia and insulin resistance
- Differences in anxiety and depression between male and female caregivers of children with a disorder of sex development
- Fasting and postprandial levels of a novel anorexigenic peptide nesfatin in childhood obesity
- The effect of growth hormone treatment on height in children with idiopathic short stature
- Clinical characteristics of type 1 diabetes over a 40 year period in Turkey: secular trend towards earlier age of onset
- Relationships of gamma-glutamyltransferase and beta 2-microglobulin on high sensitivity C-reactive protein among Japanese elementary school children
- Evaluation of insulin resistance and metabolic syndrome in a group of obese Czech children
- Circulating intact parathyroid hormone is suppressed at 25-hydroxyvitamin D concentrations >25 nmol/L in children
- Association between vitamin D level and cardiovascular risk in obese children and adolescents
- Serum paraoxonase activity and oxidative stress and their relationship with obesity-related metabolic syndrome and non-alcoholic fatty liver disease in obese children and adolescents
- Clinical features at diagnosis and responses to antithyroid drugs in younger children with Graves’ disease compared with adolescent patients
- Influence of hormonal parameters, bone mineral density and bone turnover on fracture risk in healthy male adolescents: a case control study
- Evaluation of lipid and glucose metabolism and cortisol and thyroid hormone levels in obese appropriate for gestational age (AGA) born and non-obese small for gestational age (SGA) born prepubertal Slovak children
- Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in dyslipidemic children
- Exhaled carbon monoxide in adolescents with diabetic cardiovascular autonomic neuropathy
- Gut hormone profiles in preterm and term infants during the first 2 months of life
- Outcome analysis of aromatase inhibitor therapy to increase adult height in males with predicted short adult stature and/or rapid pubertal progress: a retrospective chart review
- A deletion including exon 2 of the TSHR gene is associated with thyroid dysgenesis and severe congenital hypothyroidism
- Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) in childhood
- Patient Reports
- Neonatal diabetes in an infant of diabetic mother: same novel INS missense mutation in the mother and her offspring
- Atypical neurologic presentations of new onset type 1 diabetes mellitus in pediatric age group: a report of five unusual cases and review of the literature
- Importance of dietary calcium and vitamin D in the treatment of hypercalcaemia in Williams-Beuren syndrome
- Vitamin D intoxication in two brothers: be careful with dietary supplements
- Transient diabetes insipidus in a preterm neonate and the challenge of desmopressin dosing
- A rare case of hypoglycaemia due to insulinoma in an adolescent with acutely altered mental status
- Holoprosencephaly: ZIC2 mutation in a case with panhypopituitarism
- An association of hypochondroplasia and immune deficiency
- Hypophosphatemic rickets caused by a novel PHEX gene mutation in an Indian girl
- Psoriasis vulgaris and autoimmune polyendocrine syndrome type I: a case report
- Identification of a combined missense/splice-site mutation in FAH causing tyrosinemia type 1
- Letter to the Editor
- Vitamin D intake and premature infants with intraventricular hemorrhage: how advisable is it?
Articles in the same Issue
- Frontmatter
- Editorial
- Welcome to Assistant Editors at JPEM
- Review article
- Common approach to childhood obesity in Japan
- Images in pediatric endocrinology
- Aromatase deficiency in an adolescent girl misdiagnosed as congenital adrenal hyperplasia in infancy and childhood
- Original articles
- Prevalence of vitamin D deficiency among Iranian adolescents
- Analysis of body composition among children and adolescents – a cross-sectional study of the Polish population and comparison of body fat measurement methods
- Association of rs8066560 variant in the sterol regulatory element-binding protein 1 (SREBP-1) and miR-33b genes with hyperglycemia and insulin resistance
- Differences in anxiety and depression between male and female caregivers of children with a disorder of sex development
- Fasting and postprandial levels of a novel anorexigenic peptide nesfatin in childhood obesity
- The effect of growth hormone treatment on height in children with idiopathic short stature
- Clinical characteristics of type 1 diabetes over a 40 year period in Turkey: secular trend towards earlier age of onset
- Relationships of gamma-glutamyltransferase and beta 2-microglobulin on high sensitivity C-reactive protein among Japanese elementary school children
- Evaluation of insulin resistance and metabolic syndrome in a group of obese Czech children
- Circulating intact parathyroid hormone is suppressed at 25-hydroxyvitamin D concentrations >25 nmol/L in children
- Association between vitamin D level and cardiovascular risk in obese children and adolescents
- Serum paraoxonase activity and oxidative stress and their relationship with obesity-related metabolic syndrome and non-alcoholic fatty liver disease in obese children and adolescents
- Clinical features at diagnosis and responses to antithyroid drugs in younger children with Graves’ disease compared with adolescent patients
- Influence of hormonal parameters, bone mineral density and bone turnover on fracture risk in healthy male adolescents: a case control study
- Evaluation of lipid and glucose metabolism and cortisol and thyroid hormone levels in obese appropriate for gestational age (AGA) born and non-obese small for gestational age (SGA) born prepubertal Slovak children
- Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in dyslipidemic children
- Exhaled carbon monoxide in adolescents with diabetic cardiovascular autonomic neuropathy
- Gut hormone profiles in preterm and term infants during the first 2 months of life
- Outcome analysis of aromatase inhibitor therapy to increase adult height in males with predicted short adult stature and/or rapid pubertal progress: a retrospective chart review
- A deletion including exon 2 of the TSHR gene is associated with thyroid dysgenesis and severe congenital hypothyroidism
- Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) in childhood
- Patient Reports
- Neonatal diabetes in an infant of diabetic mother: same novel INS missense mutation in the mother and her offspring
- Atypical neurologic presentations of new onset type 1 diabetes mellitus in pediatric age group: a report of five unusual cases and review of the literature
- Importance of dietary calcium and vitamin D in the treatment of hypercalcaemia in Williams-Beuren syndrome
- Vitamin D intoxication in two brothers: be careful with dietary supplements
- Transient diabetes insipidus in a preterm neonate and the challenge of desmopressin dosing
- A rare case of hypoglycaemia due to insulinoma in an adolescent with acutely altered mental status
- Holoprosencephaly: ZIC2 mutation in a case with panhypopituitarism
- An association of hypochondroplasia and immune deficiency
- Hypophosphatemic rickets caused by a novel PHEX gene mutation in an Indian girl
- Psoriasis vulgaris and autoimmune polyendocrine syndrome type I: a case report
- Identification of a combined missense/splice-site mutation in FAH causing tyrosinemia type 1
- Letter to the Editor
- Vitamin D intake and premature infants with intraventricular hemorrhage: how advisable is it?
