The vitamin D biosynthetic enzymes include both mitochondrial (type I) and microsomal (type II) cytochrome P450 enzymes. These enzymes are heme containing, mixed function oxidases that must receive electrons from NADPH to mediate catalysis. Some infants are irritable when held, presumably due to bone pain, or develop pneumonia or seizures. Physical findings are similar to those observed in rickets due to simple vitamin D deficiency, and include enlargement of the costochondral junction of the ribs ("rachitic rosary"), enlargement of the wrists or ankles, genu varus and, in some cases, hypotonia, frontal bossing, enlarged sutures and fontanels, or craniotabes (softening of the parieto-occipital area). Radiographic examination of the long bones reveals the typical abnormalities of rickets, with widening of the metaphysis, fraying, cupping, and widening of the zone of provisional calcification, and diffuse demineralization. In most patients, hypocalcemia, hypophosphatemia, and increased serum alkaline phosphatase activity and parathyroid hormone (PTH) concentrations are observed, as is typical of patients with vitamin D deficiency rickets.