Rickets is defined as decreased or defective bone mineralization in growing children; osteomalacia is the same condition in adults. The proportion of osteoid (the organic portion of bone) is excessive. As a result, the bone becomes soft and the metaphyses of the long bones widen. In older infants, poor linear growth, bowing of the legs on weight bearing (which can be painful), thickening at the wrists and knees, and prominence of the costochondral junctions (rachitic rosary) of the rib cage occur. At this stage, x-ray findings are diagnostic.
In nutritional vitamin D deficiency, calcium is not absorbed adequately from the intestine (see Chapter 31). Poorvitamin D intake or avoidance of sunlight in infants exclusively breastfed may contribute to the development of rickets.Fat malabsorption resulting from hepatobiliary disease (biliary atresia, neonatal hepatitis) or other causes (cystic fibrosis) also may produce vitamin D deficiency because vitaminD is a fat-soluble vitamin. Defects in vitamin D metabolism by the kidney (renal failure, autosomal recessive deficiency of1α-hydroxylation, vitamin D–dependent rickets) or liver (defect in 25-hydroxylation) also can cause rickets.
In familial hypophosphatemic rickets, the major defect in mineral metabolism is failure of the kidney to adequately reabsorb filtered phosphate so that serum phosphate decreases and urinary phosphate is high. The diagnosis of this X-linked disease usually is made within the first few years of life and is typically more severe in males.
The etiology of rickets usually can be determined by an assessment of the mineral and vitamin D status (25-hydroxyvitamin D <8 ng/mL suggests nutritional vitamin D deficiency) (see Table 176-1). Further testing of mineral balance or measurement of other vitamin D metabolites may be required.
Several chemical forms of vitamin D can be used for treatment of the different rachitic conditions, but their potencies vary widely. Required dosages depend on the condition being treated (see Chapter 31). Rickets may also be treated with 1,25-hydroxyvitamin D and supplemental calcium. In hypophosphatemic rickets, phosphate supplementation (not calcium) must accompany vitamin D therapy, which is given to suppress secondary hyperparathyroidism. Adequate therapy restores normal skeletal growth and produces resolution of the radiographic signs of rickets. Nutritional rickets is treated with vitamin D given as one large dose, in weekly larger doses, or multiple smaller replacement doses. Surgery may be required to straighten legs in untreated patients with long-standing disease.
The successive sequence of chromosomal sex, gonadal sex, and phenotypic sex leads to gender identity of the individual. Genes usually determine the morphology of internal organs and of gonads (gonadal sex); this directs the appearance of the external genitalia that form the secondary sex characteristics (phenotypic sex); self-perception of the individual (gender identity) and the perception of the individual by others (gender role) follow last. In most children, these features blend and conform, but, in some patients, one or more features may not follow this sequence, leading to the disorder of sexual development (DSD) (see Chapter 23).