A 9-month old presents with failure to thrive. Electrolytes reveal a hyperchloremic metabolic acidosis. The serum phosphate is 2.0 mg/dl. Urinalysis reveals a pH of 5.5 and glucosuria.
Cystinosis
the most common inherited form of Fanconi syndrome
autosomal recessive
defect in lysosomal cystine transporter; proximal tubule cells are subsequently injured
after 6 months of life present with polydipsia, polyuria, constipation, fever, and FTT
develop corneal deposits and progressive renal failure by 10 years of age
treat with cysteamine
Cystinuria vs Cystinosis
Cystinuria (think of a CORK floating in urine, and (renal) stones sinking)
Cystinuria involves cystine, ornithine, arginine and lysine transporters.
Cystinosis only involves lysosomal cystine transporter, which causes proximal tubule cell damage. Think of the cystinURIA kid beside him, peeing, and spashing the cystinOSIS kid in the eye (corneal deposits)
Distinguish from Cystinuria, Hartnup's Disease, RTA (Distal RTA has a urine pH greater than 5.5)
CHLA Board Review 2005
The following is from PREP 2006
Cystinosis (or cystine storage disease) is an autosomal recessive disease caused by a mutation in the gene that permits the transport of cystine out of the lysosome into the cell. Cystine normally accumulates in lysosomes as part of lysosomal protein degradation. In patients who have cystinosis, massive amounts of cystine accumulate within lysosomes in almost all cells, with the disease manifested most severely in the kidney, bones, eyes, and leukocytes.
Clinically, patients who have cystinosis develop failure to thrive, renal failure, and rickets. This is due to the accumulation of cystine in the proximal tubule cells, which results in destruction of the proximal tubule. Because the proximal tubule is responsible for bulk reabsorption of sodium, bicarbonate, glucose, phosphate, and amino acids, damage to the proximal tubule in patients who have cystinosis results in massive losses of these substances in the urine. The combined losses of these substances is called Fanconi syndrome. The loss of bicarbonate results in acidosis, and the loss of phosphate results in demineralization of the bones and rickets.
The failure to thrive, blond hair, blue eyes, fair skin, markedly bowed legs, acidosis, and hypophosphatemia reported for the boy in the vignette represent the classic presentation of nephropathic cystinosis. Patients who have distal renal tubular acidosis do not have hypophosphatemia. Patients who have primary hyperparathyroidism have hypophosphatemia, but not acidosis. Secondary hyperparathyroidism is usually due to renal failure, and the boy in the vignette has only mild renal insufficiency. Finally, although hypophosphatemia is observed in vitamin D deficiency, acidosis is not part of the presentation.
The degree of renal insufficiency varies, but many patients develop end-stage renal disease within the first few years after birth and require renal replacement therapy. Dialysis is the immediate option, but renal transplantation has been shown to be successful in many patients who have cystinosis, although the extrarenal manifestations continue and need to be treated. The recent use of oral and optic cysteamine, medications designed to increase the movement of cystine out of the lysosome, has proven effective in some children who have cystinosis.
References:
* Gahl WA. Early oral cysteamine therapy for nephropathic cystinosis. Eur J Pediatr. 2003;162(suppl 1):S38-S41
* Mahoney CP, Striker GE. Early development of the renal lesions in infantile cystinosis. Pediatr Nephrol. 2000;15:50-56
* Middleton R, Bradbury M, Webb N, O'Donoghue D, Van't Hoff W. Cystinosis. A clinicopathological conference. "From toddlers to twenties and beyond." Adult-Paediatric Nephrology Interface Meeting, Manchester 2001. Nephrol Dial Transplant. 2003;18:2492-2495