CYSTINOSIS
DEFINITION:
A disorder of cystine metabolism characterized by the
accummulation of cystine resulting in renal (Fanconi Syndrome) and
ocular manifestations.
EPIDEMIOLOGY:
- incidence: 2.5/100,000
- age of onset:
- infantile form (6-18 months of age)
- late-onset form (18 months to 17 years of age)
- risk factors:
- familial - autosomal recessive
PATHOGENESIS:
- tubulointerstitial (metabolic toxins) renal disease
2. Genetic Defect
- genetic defect -> defect in the channel through which
cystine leaks from lysosomes -> a multisystemic metabolic
disorder characterized by elevated intracellular cystine
resulting in crystal deposition in lysosomes -> damage to many
organs especially the kidney
- as the proximal tubules reabsorb aa (cystine) this area is
affected first -> Fanconi syndrome; with the glomerular region
eventually affected -> decreased GRF -> chronic renal failure ->
end stage renal failure (ESRF)
CLINICAL FEATURES:
- onset - infantile (6-18 mo.), late-onset (18 months-17
years)
- episodes of vomiting, dehydration, weakness, and
unexplained fever
- anorexia, constipation
- polydipsia and polyuria
- failure to thrive and growth failure
- rickets
2. Cystinosis
- chronic renal failure (CRF) -> end stage renal failure
2. Ocular Manifestations
- refractile polychromatic crystals deposited in the
conjunctiva, cornea, sclera, and choroid
- retina
- peripheral retinopathy (beginning at 5 weeks of age)
- hypopigmented fundi with fine to course spotty
pigmentation
- photophobia
INVESTIGATIONS:
- normal anion gap hyperchloremic metabolic acidosis (with
low serum bicarbonate)
- normal or low amino acids
- normal glucose
- hypophosphatemia, hypokalemia, hypouricemia
- elevated alkaline phosphatase
2. Cystinosis
- elevated BUN and creatinine (CRF, ESRF)
2. Urine
- cystin-, ornithin-, lysin-, argininuria
2. Fanconi Syndrome
- generalized (non-specific) hyperaminoaciduria
- glucosuria, phosphaturia
- pH < 5.5 with low specific gravity (hyposthenuria)
- bicarbonaturia, hyperkaliuria, uricosuria, tubular
protein-uria, carnitinuria, low urinary ammonia
3. Biopsy
- renal - LM - proximal tubules
- cystine crystals, atrophic
- "swan neck" deformity
- glomerular
- polykaryocytosis, fused foot process
- other - pathognomonic cystine crystals in cornea,
conjunctiva, leukocytes, bone marrow, liver, spleen, lymph nodes
MANAGEMENT:
- replace inorganic and organic solutes
- vitamin D, erthropoietin, growth hormone replacement
- CRF -> dialysis, transplantation
- Aminothiol therapy - Cystagon (cysteamine bitartrate) -
depletes the lysosomes of cystine and is used to prolong
glomerular function and stimulate growth
PROGNOSIS:
- Infantile - fatal
- Late-onset - non-fatal
INTERNET LINKS:
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