Unlike cystinuria, cystinosis is very rare and the nephropathic form is thought to affect around 400 children in the US.
This autosomally recessive condition is caused by the reduced ability of the amino acid cystine to be transported out of cellular lysosomes by cystinosin, a lysosomal cystine exporter.
Who is at risk?
Three types of age-dependent cystinosis have been described, namely infantile, adolescent and adult.
Infantile cystinosis is the most common and the most aggressive of the three forms and will lead to end-stage renal failure if not treated.
Adult onset cystinosis spares the kidneys and only affects the eyes.
How does it manifest?
Crystals form in the kidneys that ultimately present as Fanconi syndrome.
Fanconi syndrome, of which cystinosis is the commonest cause, is caused by proximal renal tubular defects in which failure to reabsorb causes excess loss and increased urinary excretion of sodium, potassium, amino acids, calcium, phosphate, bicarbonate and glucose.
Presenting features include failure to thrive, delay in sexual development, polyuria, polydyspsia and hypophosphatemic rickets/osteomalacia.
Eye disease may cause photophobia and ultimately blindness through retinopathy.
Cystine crystals can also accumulate in other tissues causing endocrinopathies, liver disease, bone marrow and CNS disorders. Endocrinopathies include pituitary and thyroid dysfunction, and pancreatopathies such as diabetes mellitus. Liver involvement may be signalled by deranged LFTs and hepatomegaly.
Cerebral calcification and atrophy may be noted on imaging. Gastrointestinal complications include swallowing problems and reflux disease.
How is it managed?
Management requires good family and multidisciplinary support.
Indometacin can reduce the renal effects of cystinosis by, in part, increasing sensitivity to ADH. Fluid and electrolyte management includes adequate hydration, electrolyte and vitamin D replacement.
Monitoring for and treatment of complications is initiated as they arise, such as diabetes mellitus and thyroid disease. Growth hormone replacement may be used in infant and adolescent disease in order to reach acceptable growth potential. PPIs are indicated for gastrointestinal reflux disease although surgical interventions such as Nissen’s fundoplicaton may be required.
Oral phosphocysteamine therapy has been shown to delay the time to renal replacement therapy. Eventually, renal transplantation is required.
Dr Thakkar is a GP in Wooburn Green, Buckinghamshire