Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Hereditary Rickets

Rickets is defined by a deficiency in vitamin D resulting in growth retardation and bone deformity.

Test Strategy

The differentiation of rickets starts with vitamin D (colecalciferol) substitution when hypercalcemia is excluded. In cases where in spite of this therapy a low concentration of 1,25-dihydroxy vitamin D3 can be found and a kidney disease can be excluded a defect in 1-alpha hydroxylation can be suspected. In cases where 1,25-dihydroxy vitamin D3 is normal a vitamin D receptor defect must be taken into account.

Pathogenesis

The disease is most often caused by inadequate intake of vitamin precursors or insufficient exposure to sun light. Some rare hereditary forms are due to mutations of the vitamin D activating enzyme (type 1) or the vitamin D receptor (type 2).

Systematic

Metabolic bone disease
Hereditary Rickets
Hypophosphatasia
Adult hypophosphatasia
ALPL
Childhood hypophosphatasia
ALPL
Infantile hypophosphatasia
ALPL
Odontohypophosphatasia
ALPL
Hypophosphatemic bone and kindney disease
Disorders of the renal phosphate transporters
Hypophosphatemic rickets with hypercalciuria
SLC34A3
Idiopathic basal ganglia calcification 1
SLC20A2
Nephrolithiasis/osteoporosis, hypophosphatemic, 1
SLC34A1
Nephrolithiasis/osteoporosis, hypophosphatemic, 2
SLC9A3R1
FGF23-induced hypophosphatemic rickets
Autosomal dominant hypophosphatemic rickets
FGF23
Autosomal recessive hypophosphatemic rickets type 1
DMP1
Autosomal recessive hypophosphatemic rickets type 2
ENPP1
X-linked dominant hypophosphatemic rickets
PHEX
Fanconi-type hypophosphatemic rickets
Nephrolithiasis/osteoporosis, hypophosphatemic, 1
SLC34A1
X-linked recessive hypophosphatemic rickets
CLCN5
OCRL
Hypophosphatemic rickets with hyperparathyroidism
KL
Osteoglophonic dysplasia
FGFR1
Raine syndrome
FAM20C
X-linked dominant hypophosphatemic rickets
PHEX
Vitamin D hydroxylation-deficient rickets type 1A
CYP27B1
Vitamin D hydroxylation-deficient rickets type 1B
CYP2R1
Vitamin D-dependent rickets, type 2A
VDR
Vitamin D-dependent rickets, type 2B
RXRA
Inherited human diseases of heterotopic bone formation
Osteopetrosis
Osteoporosis/renal Osteodystrophy
Pseudohypoparathyroidism

References:

1.

Kato S et al. (2002) Molecular genetics of vitamin D- dependent hereditary rickets.

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2.

Econs MJ et al. (1997) Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder.

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3.

et al. (2000) Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.

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4.

Scriver CR et al. (1977) Hypophosphatemic nonrachitic bone disease: an entity distinct from X-linked hypophosphatemia in the renal defect, bone involvement, and inheritance.

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5.

Scriver CR et al. (1981) Autosomal hypophosphataemic bone disease responds to 1,25-(OH)2D3.

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Update: Sept. 26, 2018