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Average 4.3 of 31 Ratings
Low serum phosphate and normal calcium levels are found in what common etiology of hereditary rickets?
Vitamin D-dependent, type I
Vitamin D-dependent, type II
Autosomal dominant hypophosphatemic
Jansen's metaphyseal chondrodysplasia
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Low serum phosphate and normal calcium levels are found in X-linked hypophosphatemic rickets.
X-linked hypophosphatemic rickets is the most common form of hereditary rickets. It is an X-linked dominant disorder which has been linked to the PHEX gene. Laboratory findings of this disorder include low serum phosphate, normal serum calcium and 25 hydroxycholecalciferol levels, and inappropriately low 1,25-dihydroxyvitamin D3.
Carpenter et al. showed hypophosphatemic rickets was initially referred to as “vitamin D resistant rickets” due to its lack of response to therapeutic vitamin D. Current treatment with activated vitamin D metabolites (calcitriol or alfacalcidol) and phosphate salts have been shown to help with this condition.
Illustration A shows an insufficiency fracture of the proximal tibia in an adult patient with X-linked hypophosphatemic rickets. A stress fracture on the medial tibia may be a presenting feature of untreated disease.
Answer 2: Vitamin D-dependent rickets, type I, is a rare autosomal recessive disorder.
Answer 3: Vitamin D-dependent rickets, type II, is a rare autosomal recessive disorder, most often caused by mutations in the vitamin D receptor gene.
Answer 4: Autosomal dominant hypophosphatemic results from a rare mutation in the fibroblast growth factor 23 (FGF23) gene.
Answer 5: Jansen's metaphyseal chondrodysplasia is a skeletal dysplasia that results from ligand-independent activation of the type 1 parathyroid hormone receptor (PTHR1).
Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL
J. Bone Miner. Res.. 2011 Jul;26(7):1381-8. PMID: 21538511 (Link to Abstract)
Carpenter, JBMR 2011
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Average 3.0 of 9 Ratings
Laboratory values of a normal serum calcium and parathyroid hormone can be found in which of the following disease states?
Type I vitamin D deficient rickets
Type II vitamin D deficient rickets
X-linked hypophosphatemic rickets
Hypophosphatemic rickets is caused by the inability of kidney proximal tubules to reabsorb phosphate due to a mutated PHEX gene, found on the X chromosome. PHEX is thought to protect extracellular matrix glycoproteins from proteolysis. Hypophosphatemic rickets shares many clinical similarities with nutritional rickets but shows PTH levels that are not elevated, even with calcium and phosphate abnormalities.
Pettifor reviews the advances in molecular genetics in the understanding and possible treatments in tumour-induced osteomalacia/rickets.
The review article by Carpenter discusses the X-linked disorder including its clinical manifestations, the wide spectrum of disease severity, and complications of the disease in adult patients.
Illustration A is a table that details the laboratory values associated with each type of rickets.
Eur. J. Pediatr.. 2008 May;167(5):493-9. PMID: 18214537 (Link to Abstract)
Pettifor, EJOP 2008
Pediatr Clin North Am. 1997 Apr;44(2):443-66. PMID: 9130929 (Link to Abstract)
Average 2.0 of 23 Ratings
You are seeing a 4-year-old girl for leg deformities on a mission trip to Haiti. Clinical photograph and radiographs of her lower extremities and wrist are shown in Figures A-C. What laboratory studies would help confirm a nutritional deficiency as opposed to an X-linked genetic disorder as a cause of her condition?
Low serum phosphate, elevated alkaline phosphatase, elevated PTH
Low serum phosphate, elevated alkaline phosphatase, normal PTH
Low serum phosphate, elevated alkaline phosphatase, decreased PTH
Elevated serum phosphate, elevated alkaline phosphatase, elevated PTH
Elevated serum phosphate, decreased alkaline phosphatase, decreased PTH
The key laboratory factor that differentiates nutritional from hypophosphatemic rickets is an elevated PTH. Tortolani et al. review the differential diagnosis of bone mineral density deficiency in their JAAOS review. As discussed, nutritional rickets shows low to normal serum calcium, low serum phosphate, elevated alkaline phosphatase, and elevated parathyroid hormone. While nutritional rickets is due to dietary deficiency, hypophosphatemic rickets is caused by the inability of kidney proximal tubules to reabsorb phosphate due to mutated PHEX gene, found on the X chromosome. PHEX is thought to protect extracellular matrix glycoproteins from proteolysis. Hypophosphatemic rickets shares many clinical manifestations with nutritional rickets, but shows PTH levels that are not elevated, even with calcium and phosphate abnormalities (pseudohypoparathyroidism). Loeffler and Sherman evaluated the addition of phosphate to the standard vitamin D therapy in hypophosphatemic rickets on long-term growth and deformity correction. They found no additional benefit of this therapy and as such, it is currently not recommended. Ferris et al. review their treatment of 19 patients with hypophosphatemic rickets and found that staged surgical intervention afforded better results but these patients, even with intervention, developed early degenerative joint disease.
Tortolani PJ, McCarthy EF, Sponseller PD
J Am Acad Orthop Surg. 10(1):57-66. PMID: 11809051 (Link to Abstract)
Tortolani, JAAOS 2002
Ferris B, Walker C, Jackson A, Kirwan E.
J Pediatr Orthop. 1991 May-Jun;11(3):367-73. PMID: 2056087 (Link to Abstract)
Ferris, JPO 1991
Loeffler RD Jr, Sherman FC.
Clin Orthop Relat Res. 1982 Jan-Feb;(162):4-10. PMID: 6279346 (Link to Abstract)
Loeffler, CORR 1982
Average 3.0 of 20 Ratings
Loss of function in the 25(OH) vitamin D1-alpha hydroxylase gene causes which of the following diseases?
Vitamin D resistant rickets
Hereditary Vitamin D dependant rickets type I
Hereditary Vitamin D dependant rickets type II
Loss of function mutations in the 25 (OH) vitamin D hydroxylase gene cause hereditary vitamin D dependant rickets type I. Hereditary vitamin D dependant rickets type II is caused by a defect in intracellular receptor for 1,25-(OH)2-vitamin D3. Both forms of hereditary vitamin D dependent rickets show decreased serum calcium/phosphorous, elevated alkaline phosphatase/PTH, but type I has a decrease in the 1,25(OH)2 vitamin D and type II shows a increase in 1,25(OH)2 vitamin D. Vitamin D resistant rickets (Familial Hypophosphatemic Rickets) is caused by a large deletion in the PHEX gene and results in low serum phosphorous, elevated alkaline phosphatase, and normal calcium. Hyperphosphatemia can be caused by mutation in the GALNT3 gene and results in elevated serum phosphate and decreased PTH/calcium.
Kato et al. describe the molecular physiology of vitamin D metabolism and the recognized gene mutations associated with various clinical manifestations of mutations in vitamin D homeostasis.
Mol Cell Endocrinol. 1999 Oct 25;156(1-2):7-12. PMID: 10612418 (Link to Abstract)
Which of the following laboratory values would be consistent with nutritional rickets?
increased calcium level
increased phosphate level
decreased alkaline phosphatase level
increased vitamin D level
increased parathyroid hormone level
With decreased vitamin D intake, intestinal calcium and phosphate absorption are reduced leading to hypocalcemia. Decreased serum calcium stimulates increased PTH (secondary hyperparathyroidism) that leads to bone resorption resulting in low to normal levels of serum calcium. Overall laboratory studies show low to normal calcium, low phosphate (excreted because of effect of PTH), increased PTH, low levels of vitamin D and increased alkaline phosphatase levels.
Average 4.0 of 11 Ratings
The active form of vitamin-D (calcitriol) is produced by the enzyme 1-alpha-hydroxylase. What hormone activates this enzyme?
thyroid stimulating hormone (TSH)
parathyroid hormone (PTH)
The precursor to calcitriol is stored in the skin where UV exposure converts it to previtamin D3. Then, it is bound to vitamin-D binding protein (DBP) where it is carried to the liver and metabolized to 25-hydroxyvitamin D. When calcium is low, parathyroid hormone (PTH) levels become elevated which activates 1-alpha-hydroxylase which converts it to the active Vitamin D (calcitriol). Its most potent effect is to enhance intestinal calcium absorption through DNA regulation. Illustration A shows a diagram of Vitamin D metabolism.
Average 3.0 of 16 Ratings