Fibroblast growth factor23 (FGF-23)

1. Decreases renal tubular reabsorption of phosphate and therefore decreases serum phosphorus. 2. Decreases the activity of renal 1-hydroxylase, resulting in a decrease in the production of 1,25-D.

Rickets
Is a disease of growing bone that is due to unmineralized matrix at the growth plates and occurs in children only before fusion of the epiphyses. Causes:

 Clinical Features: Craniotabes is a softening of the cranial bones and can be detected by applying pressure at the occiput or over the parietal bones. The sensation is similar to the feel of pressing into a Ping-Pong ball and then releasing. Widening of the costochondral junctions results in a rachitic rosary. Growth plate widening is also responsible for the enlargement at the wrists and ankles. Harrison groove occurs from pulling of the softened ribs by the diaphragm during inspiration.

Radiology: 1. Thick growth plate. 2. Cupping of distal end. 3. Wide metaphysis.

Clinical Evaluation
Because the majority of children with rickets have a nutritional deficiency, the initial evaluation should focus on a dietary history, emphasizing intake of vitamin D and calcium. Most children in industrialized nations receive vitamin D from formula, fortified milk, or vitamin supplements. Along with the amount, the exact composition of the formula or milk is pertinent, because rickets has occurred in children given products that are called milk (soy milk) but are deficient in vitamin D and/or minerals. Cutaneous synthesis mediated by sunlight exposure is an important source of vitamin D. It is important to ask about time spent outside, sunscreen use, and clothing, especially if there may be a cultural reason for increased covering of the skin. Because winter sunlight is ineffective at stimulating cutaneous synthesis of vitamin D, the season is an additional consideration. Children with increased skin pigmentation are at increased risk for vitamin D deficiency because of decreased cutaneous synthesis. The presence of maternal risk factors for nutritional vitamin D deficiency, including diet and sun exposure, is an important consideration when a neonate or young infant has rachitic findings, especially if the infant is breast-fed. Determining a child's intake of dairy products, the main dietary source of calcium, provides a general sense of calcium intake. High dietary fiber can interfere with calcium absorption. The child's medication use is relevant, because certain medications such as the anticonvulsants, phenobarbital and phenytoin increase degradation of vitamin D, and aluminum-containing antacids interfere with the absorption of phosphate. Malabsorption of vitamin D is suggested by a history of liver or intestinal disease. Undiagnosed liver or intestinal disease should be suspected if the child has gastrointestinal (GI) symptoms, although occasionally rickets is the presenting complaint. Fat malabsorption is often associated with diarrhea or oily stools, and there may be signs or symptoms suggesting deficiencies of other fat-soluble vitamins (A, E, and K; Chapters 45, 49, and 50Chapter 45 Chapter 49 Chapter 50). A history of renal disease (proteinuria, hematuria, urinary tract infections) is an additional significant consideration, given the importance of chronic renal failure as a cause of rickets. Polyuria can occur in children with chronic renal failure or Fanconi syndrome. Children with rickets might have a history of dental caries, poor growth, delayed walking, waddling gait, pneumonia, and hypocalcemic symptoms. The family history is critical, given the large number of genetic causes of rickets, although most of these causes are rare. Along with bone disease, it is important to inquire about leg deformities, difficulties with walking, or unexplained short stature, because some parents may be unaware of their diagnosis. Undiagnosed disease in the mother is not unusual in X-linked hypophosphatemia. A history of a unexplained sibling death during infancy may be present in the child with cystinosis, the most common cause of Fanconi syndrome in children. The physical examination focuses on detecting manifestations of rickets (see Table 48-3). It is important to observe the child's gait, auscultate the lungs to detect atelectasis or pneumonia, and plot the patient's growth. Alopecia suggests vitamin D-dependent rickets type 2. The initial laboratory tests in a child with rickets should include serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, creatinine, and electrolytes (see Table 48-4 for interpretation). Urinalysis is useful for detecting the glycosuria and aminoaciduria (positive dipstick for protein) seen with Fanconi syndrome. Evaluation of urinary excretion of calcium (24 hr collection for calcium or calcium:creatinine ratio) is helpful if hereditary hypophosphatemic

rickets with hypercalciuria or Fanconi syndrome is suspected. Direct measurement of other fat-soluble vitamins (A, E, and K) or indirect assessment of deficiency (prothrombin time for vitamin K deficiency) is appropriate if malabsorption is a consideration.