Bone Complications of Cystinosis.

Cystinosis is recognized as a systemic disease because of mutations in the gene encoding cystinosin, the lysosomal cystine exporter. In the nephropathic form that affects infants and young children, the kidney Fanconi syndrome leads to metabolic acidosis, hypophosphatemia attributable to phosphaturia, and reduced synthesis of the active metabolite of vitamin D, 1,25-dihydroxyvitamin D3, also known as calcitriol. These resultant biochemical abnormalities do not allow the adequate mineralization of osteoid made by the osteoblast and result in a classic feature of nephropathic cystinosis, rickets. In addition, it has been recognized recently that cystinosin is expressed by osteoblasts, and mutations in cystinosin may lead to a reduction in the ability of osteoblast precursor cells to transform into mature osteoblasts capable of synthesizing osteoid, thus, leading to defective mineralization. Contemporary treatment of patients with rickets in cystinosis includes provision of pharmacologic phosphate salts, correction of the metabolic acidosis with supplemental alkali, and generally, provision of calcitriol. Experimental evidence provides rationale that cystine-depleting therapy with cysteamine bitartrate helps to restore osteoblast function toward normal as well. Thus, the contemporary infant with nephropathic cystinosis should have rickets treated and cured within a short time after the diagnosis is made. Some reports of copper deficiency have arisen in nephropathic cystinosis as a consequence of the kidney Fanconi syndrome loss of urinary copper. Copper is an essential co-factor in collagen fibril arrangement and in osteoid mineralization. At present, it remains unknown whether we should be supplementing copper to our patients with nephropathic cystinosis, but it is hoped that emerging studies will help direct this soon. As patients with cystinosis now routinely survive well into adulthood years, additional challenges to life-long bone health have emerged and will be reviewed herein.