Vitamin D-Resistant Rickets is also known as:
Familial Hypophosphatemia
[NOTE April 14, 1997: Several of us in the
F-HYPDRR mailing list
feel that some of
the information below is out of date. Join us and find out more about
the syndrome, and current methods of treatment]
DEFINITION:
A rare x-linked dominant disorder characterized by failure to
thrive, short stature, and rickets.
EPIDEMIOLOGY:
- incidence: 1-10/1,000,000 live births [current estimates are
higher, at 1 in 20,000 (due to standard Vitamin D dietary
supplementation in the Northern Hemisphere, Vitamin D Sensitive
Rickets is almost unheard of, and Vitamin D Resistant Rickets is
now the most common form of rickets here)]
- age of onset: early infancy -> 15 months
- risk factors:
o familial - x-linked dominant (also autosomal recessive and
sporadic forms)
+ chrom.#:
Xp22.2-p22.1
+ gene: ? [now called the PHEX gene]
PATHOGENESIS:
1. Genetic Defect
- genetic defect -> 2 effects on the kidney
+ interferes with proximal tubular reabsorption of phosphate
+ interferes with conversion of 25(OH)D
to 1,25 (OH)2D
- there may be a coexistent deficiency of transepithelial
absorption of phosphate in the intestine
- growth is normal in early infancy until the serum phosphate
levels fall to low values at about 6 months of age
CLINICAL FEATURES:
1. Musculoskeletal Manifestations
- smooth bowing of lower extremities when begin to weight bear
- waddling gait
- coxa vara
- genu varus and valgum
- short stature
- dolichocephaly
- no Harrison groove
2. Dental Manifestations
- pulp deformities
- "intraglobular dentin" tooth anomaly
- occasional enamal defects
- periapical infections
INVESTIGATIONS:
1. Serum
- normal calcium
- hypophosphatemia
- elevated alkaline phosphatase
- low to normal serum 1,25 (OH2)D levels
- normal PTH
2. Urine
- hyperphosphaturia
- normal amino acids
3. Imaging Studies
1. Skeletal X-Rays
- evidence of rickets or osteomalacia
- coarse-appearing trabecular bone
- metaphyseal widening and fraying
- cupping of metaphysis at proximal and distal tibia and at
distal femur, radius, and ulna
MANAGEMENT:
1. Medical
1. Oral Phosphate Supplements
- dibasic sodium phosphate
- phosphoric acid
+ side effects: diarrhea
2. Vitamin D Analog
2. Surgery
- osteotomy for existing limb deformities
3. Prognosis
- adult height: 130-165 cm (untreated); 170 cm (treated)
- normal life span