Cystinosis

Cystinosis is an autosomal recessive lysosomal storage disease caused by mutations in CTNS, encoding cystinosin, the lysosomal cystine transporter, leading to accumulation of cystine crystals in tissues.

• Prevalence about 1 in 100,000 to 200,000.
• Forms: infantile nephropathic (95%, onset 6 to 12 months), juvenile (intermediate, onset 8 to 12 years), adult/ocular non-nephropathic (corneal crystals only).
• Multisystem: renal Fanconi syndrome, then progressive glomerular damage and ESKD by 10 years if untreated; hypothyroidism, photophobia, myopathy, diabetes, hypogonadism, swallowing difficulty, central nervous system involvement, hepatomegaly.
• Treatment with cysteamine dramatically improves outcomes and delays ESKD.

• Infancy: failure to thrive, polyuria, polydipsia, vomiting, dehydration, rickets, hypophosphataemia, constipation.
• Photophobia from corneal cystine crystals (by 1 year), blue-eyed, fair-haired children (hypopigmentation).
• Hypothyroidism, growth failure, delayed puberty.
• Later: renal failure (age 6 to 12), diabetes, myopathy, swallowing disorder, neurological complications (cognitive decline, stroke-like events), retinopathy.

• Fanconi syndrome (proximal RTA, glycosuria, aminoaciduria, phosphaturia, hypokalaemia, low molecular weight proteinuria).
• White cell cystine level (elevated, over 2 nmol half-cystine/mg protein; normal under 0.2) is diagnostic.
• Slit-lamp examination of the cornea: needle-shaped cystine crystals.
• CTNS genetic testing (common 57-kb deletion in European populations).
• Prenatal diagnosis by chorionic villus cystine or CTNS genetics.
• Baseline thyroid function, glucose, bone profile, renal function, vitamin D, growth, swallowing and neurological assessments.

• Cysteamine bitartrate immediate release 1.3 g/m2/day divided every 6 hours (start low to reduce gastrointestinal effects, titrate to white cell cystine under 1 nmol half-cystine/mg protein measured 5 to 6 hours after the dose), or delayed-release cysteamine 1.3 g/m2 twice daily (every 12 hours); lifelong. Early start slows renal deterioration and prevents extrarenal complications.
• Cysteamine eye drops (0.55%) hourly while awake to dissolve corneal crystals.
• Replace Fanconi losses: sodium bicarbonate or citrate 5 to 15 mmol/kg/day, potassium 3 to 10 mmol/kg/day, phosphate 30 to 60 mg/kg/day elemental, vitamin D (calcitriol 20 to 50 ng/kg/day), fluid and sodium chloride, carnitine supplementation.
• Indomethacin (1 to 3 mg/kg/day) to reduce polyuria.
• Hormonal: levothyroxine, insulin, testosterone, growth hormone (0.05 mg/kg/day) for severe growth failure.
• Renal replacement: dialysis, kidney transplantation (disease does not recur in graft; continue cysteamine for extrarenal disease).
• Nutrition, swallowing therapy, gastrostomy if necessary; neurological and ophthalmology follow-up.
• Monitor cystine levels, electrolytes, renal function, thyroid, glucose, growth and bone health regularly.