All of the findings and chemical abnormalities are similar to those seen in the classic nutritional deficiency syndrome, with the exception of the concentrations of the polar metabolites of vitamin D. In the first form of the disorder—failure of conversion of 25(OH)D to 1,25(OH)₂D in the kidney—serum levels of 25(OH)D may be very high (hence, the term pseudo) while levels of 1,25(OH)₂D may be low. In the latter form of the disorder—end-organ insensitivity to the action of 1,25(OH)₂D—the serum levels of both 25(OH)D and 1,25(OH)₂D are usually normal or high. Both forms are often successfully treated with administration of 1,25(OH)₂D.

A specific disorder that fits into the so-called pseudodeficiency is oncogenic osteomalacia. This syndrome is due to mesenchymal tumors that develop in adults for unknown cause. These tumors are often very small, subcutaneous, and, more often than not, benign. However, these tumors secrete FGF-23 and induce renal phosphate wasting and hypophosphatemia and inhibit renal production of 1,25(OH)₂D. Hence, the classical biochemical triad is hypophosphatemia, normal 25(OH)D, and low 1,25(OH)₂D. Serum levels of FGF-23 are available clinically and can help confirm the diagnosis. Although patients with oncogenic osteomalacia can have symptomatic improvement with oral phosphorus and 1,25(OH)₂D replacement, the cure is finding the mesenchymal tumor responsible for producing FGF-23 and having it removed. The latter is often a diagnostic challenge because these tumors are small and may be located anywhere in the human body. The radioisotope, octreotide, is taken up by these tumors such that periodic scans, often with positron emission tomographic accentuation, are necessary to find these tumors. Removal of the tumor is a cure. Total tumor removal will be accompanied by normalization of the BSAP, serum phosphorus, 1,25(OH)₂D, and FGF-23 levels and the patient will never again need oral phosphorus or 1,25(OH)₂D replacement.

VITAMIN D–RESISTANT RICKETS DUE TO RENAL TUBULAR ACIDOSIS

The group of diseases classified under renal tubular acidosis includes metabolic disorders of diverse and multiple causes (see Plate 3-19). The basic mechanism common to them all is the kidney’s inability to substitute hydrogen ions for fixed base. The diseases are now subclassified into three types. In type I (classic or distal), proton exchange is defective; in type II (proximal), the cause appears to be a failure of reabsorption of bicarbonate in the proximal tubule; and in type IV (generalized distal), through one of several mechanisms, the excretion of both hydrogen and potassium ions in the distal tubule is defective. (Type III is a poorly defined mixture of types I and II and is usually excluded from current classifications.)