Early oral cysteamine therapy for nephropathic cystinosis.
Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder in which intracellular cystine accumulates due to impaired transport out of lysosomes. The clinical manifestations include renal tubular Fanconi syndrome in the 1st year of life, with hypophosphatemic rickets, hypokalemia, polyuria, dehydration and acidosis, growth retardation, hypothyroidism, photophobia, renal glomerular deterioration by 10 years of age, and late complications such as myopathy, pancreatic insufficiency, and retinal blindnesss. The cystinosis gene, CTNS, codes for cystinosin, a 367 amino acid protein with seven transmembrane domains. More than 50 CTNSmutations have been identified, but approximately 50% of Northern European patients have a 57257-bp deletion which removes the first nine exons of CTNS. The mainstay of cystinosis therapy is oral cysteamine (Cystagon). This aminothiol can lower intracellular cystine content by 95%, and has proven efficacy in delaying renal glomerular deterioration, enhancing growth, preventing hypothyroidism, and lowering muscle cystine content. Its early and diligent use is critical; in one study, for every month of treatment prior to 3 years of age, 14 months' worth of later renal function were preserved. Several examples of individual patients treated early and having preserved renal function and normal growth are available. Newborn screening using a chip containing cDNA to detect common CTNSmutations may allow diagnosis and treatment in the first weeks of life.


CONCLUSIONS
Early diagnosis and treatment of nephropathic cystinosis can change the course of this disease.
Gahl
William A
WA
Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, MSC 1851 Building 10, Room 10C-103, 10 Center Drive, Bethesda, Maryland 20892-1851, USA. bgahl@helix.nih.gov
D000284:Administration, Oral; D003543:Cysteamine / Q000008:administration & dosage / Q000627:therapeutic use*; D003554:Cystinosis / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D011837:Radiation-Protective Agents; D003543:Cysteamine