Management of Chronic Kidney Disease

Cystinosis is an autosomal recessive condition characterised by the excessive intracellular storage of the amino acid cystine.  Three variants are recognised, depending on the clinical course and intracellular cystine content:

• Benign or adult cystinosis - cystine crystals in the cornea and bone marrow only and the mildest elevation in intracellular cystine levels.  No renal disease.
• Infantile or nephropathic cystinosis - commonest form, associated with the highest intracellular cystine levels.
• Adolescent form - intermediate levels of cystine.

The abnormality is in a mebrane protein, cystostatin, which is responsible for transporting cystine out of lysosomes. Ingested protein normally enters the lysosome, where acid hydrolases degrade it to its component amino acids, including cysteine. This amino acid is readily oxidized within the lysosome to cystine, and both cystine and cysteine can normally enter the cytoplasm, where cystine is converted rapidly to cysteine by the reducing agent, glutathione. Cytoplasmic cysteine is incorporated into protein or degraded to inorganic sulphate for excretion. Absence of cystostatin leads to accumulation of cystine within lysosomes forming birefringent, hexagonal, or rectangular crystals that impair cellular energy metabolism.

Symptoms of Fanconi's syndrome appear in the latter half of the first year of life. Rickets and growth failure occurs before renal function declines. Cystine crystals form in the cornea, causing photophobia. Other later complications include hypothyroidism, splenomegaly and hepatomegaly as cystine acculmulates in all tissues.

Renal impairment is an ealry problem in untreated patients.

Treatment is based on the chemical cysteamine. This enters the lysosome and combines with cystine to form cysteine and the mixed disulfide cysteamine-cysteine both of which can exit the lysosome via the transport system for cationic amino acids, which works normally in cystinosis.

Further internet sites: http://emedicine.medscape.com/article/981650-overview

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