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Cystinosis is an inherited metabolic disease resulting in the accumulation of cystine in various organs of the body (e.g., kidneys, eyes, liver, muscles, pancreas, brain, leukocytes). Untreated, the infantile nephropathic form will result in end-stage renal failure before the age of 10 years.

Estimated to be in the range of 1:100,00-200,000 live births, although a wide geographic variability has been reported. Males are slightly more often affected (M:F = 1.5:1). Cystinosis is the most common inherited cause of De Toni-Debré-Fanconi syndrome (renal Fanconi syndrome).

All types of cystinosis are transmitted in an autosomal recessive manner. The defect affects the cystinosin gene (CTNS) that has been mapped to 17p13. Hitherto, more than 50 different CTNS mutations have been described.

Cystine is a degradation product of cysteine, which originates from ingested and in lysosome hydrolyzed proteins. Cystinosis is a lysosomal storage disease caused by impaired transport of cystine out of the lysosomes into the cytoplasm. This energy-dependent transport relies on cystinosin, an integral membrane protein that acts as the lysosomal cystine transporter. In the nephropathic form of cystinosis (see Diagnosis and Clinical aspects), this results in cystine depositions within the cells of various organs where they affect the cellular energy metabolism. Cystine crystal deposits in the proximal tubule cells of the kidney result in early renal involvement and eventually renal Fanconi syndrome. It is characterized by a generalized transport defect in the proximal tubules of the kidneys with renal losses of glucose, phosphate, calcium, uric acid, amino acids, and bicarbonates eventually leading to short stature, osteomalacia, and renal failure.

Infantile nephropathic cystinosis (Synonyms: Classic or early onset cystinosis): The diagnosis is based on growth retardation manifesting after the first six months of life and the features of renal Fanconi syndrome before one year of age with progressive deterioration of renal function to end-stage renal disease usually before the age of 10 years. Measurement of leukocyte cystine content is used to confirm the diagnosis. Cystine crystals can be detected in the cornea and conjunctiva and in biopsies from brain, bone marrow, kidneys, liver, spleen, pancreas, intestinal mucosa, thyroid, lymph nodes, and muscles.

Intermediate nephropathic cystinosis (Synonyms: Juvenile, adolescent, or late onset cystinosis): This form of cystinosis is basically characterized by the same renal pathology, however the onset is delayed and the severity (initially) less pronounced. In the beginning, the symptoms of renal Fanconi syndrome in these patients can be so subtle that they diagnosis may be missed for a while. However, eventually renal function also decreases in these patients and end-stage renal failure develops between the age of 15 and 25 years.

Non-nephropathic cystinosis (Synonyms: Benign, adult or ocular cystinosis): These patients present with photophobia and ocular discomfort (burning, pruritus) secondary to cystine crystal accumulation in the corneae (and conjunctivae), which can easily be detected on slit lamp examination. Crystalline deposits are also detected in bone marrow and leukocytes (but not ...

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