CTNS Gene Mutation, chromosome 17

  1. CTNS Gene Mutation, chromosome 17.

  2. Infantile and Juvenile are nephropathic, the adult is not.

  3. Kidneys are the first organ affected in Infantile, manifesting with aminoaciduria first weeks of intrauterine life f/b glucosuria, phosphaturia and urinary HCO3 loss in the later trimesters. By 6 months of age, an infant can have full-blown Fanconi’s syndrome.

  4. In infantile form, In most patients <2 years of age GFR is normal. Will reach ESRD by the end of the first decade of life.

  5. Juvenile is a milder version of infantile. Disease progression is much slower.

  6. Renal biopsy usually not required. When done, can show “Swan Neck deformity” of Proximal tubules. Cystine deposition within interstitium, but not in tubular cells.

7.Late onset can manifest with glomerular disease like FSGS.

Extrarenal manifestations of cystinosis:

  1. Corneal deposits (not improved by systemic cysteamine treatment, topical eye drops may help )

  2. Hypothyroidism due to crystal formation in follicular cells of thyroid, leading to fibrosis and atrophy. Present in 75% of individuals.

  3. Hypergonadotrophic hypogonadism is common.

  4. Type 1 diabetes

  5. Hepatomegaly related to enlarged kupffer cells that transform into large foam cells containing cystine crystals

  6. Distal myopathy >> Proximal

  7. Normal intelligence, cognitive dysfunction can occur later in life, cortical atrophy, basal ganglia calcification, ischemia, demyelination seen.

Treatment : Cysteamine depletes lysosomal cystine content by a disulphide exchange reaction with cystine. Given at dose of 1.3-1.9g/m2 in four daily doses. Main side effect is gastric intolerance.