According to GeneReviews (Cystinosis, NCBI Bookshelf), cystinosis results from pathogenic variants in the CTNS gene, which encodes the lysosomal cystine transporter cystinosin; the known_genes field of this packet does not independently list a gene, and genetic attribution here derives exclusively from the certified GeneReviews chapter. The disorder follows an autosomal recessive inheritance pattern, as GeneReviews genotype-phenotype data establishes that truncating CTNS pathogenic variants and the 57-kb deletion produce nephropathic cystinosis when present in homozygous form. GeneReviews notes that individuals with apparent residual cystinosin activity, typically those carrying missense variants, often present with later-onset or ocular phenotypes. The 57-kb deletion represents more than 50% of CTNS pathogenic variants in individuals of Northern European ancestry but has not been reported in populations from the Middle East, according to GeneReviews. Disruption of cystinosin function prevents normal cystine export from lysosomes, leading to intralysosomal cystine crystal accumulation and progressive cellular and organ damage.

Per GeneReviews, nephropathic cystinosis is suspected in infants and young children presenting with poor weight gain and growth deficiency appearing by six to twelve months of age, feeding difficulties, vomiting, severe polyuria, polydipsia, dehydration, and progressive rachitic skeletal changes. Corneal cystine crystals, observed by slit lamp examination, are typically detectable in most individuals by twelve months of age and in virtually all affected individuals by eighteen months. Laboratory findings supporting the diagnosis include hypochloremic metabolic acidosis, renal Fanconi syndrome markers (increased urinary excretion of electrolytes, glucose, and amino acids), hypocalcemia, hypophosphatemia, hypokalemia, and elevated serum alkaline phosphatase. Elevated cystine concentration in polymorphonuclear leukocytes, cultured fibroblasts, or placenta constitutes a definitive laboratory finding per GeneReviews. Imaging may reveal radiographic features of rickets and renal ultrasound abnormalities including medullary nephrocalcinosis.

PROCYSBI (cysteamine bitartrate), an FDA-approved treatment recorded in this packet (NDA, CDER, approved April 2013), represents the primary systemic therapy for cystinosis; it is a delayed-release formulation of cysteamine designed to deplete lysosomal cystine. GeneReviews additionally documents Cystaran (cysteamine hydrochloride ophthalmic solution 0.44%), an FDA-approved therapy indicated specifically for the treatment of corneal cystine crystal accumulation in cystinosis patients, listed as an approved orphan drug in this packet. GeneReviews states there is no cure for cystinosis and emphasizes that multidisciplinary management involving specialists in nephrology, metabolic disease, ophthalmology, neurology, gastroenterology, nutrition, and psychology is the standard approach. GeneReviews notes that cysteamine therapy, while not curative, dramatically improves overall prognosis and life span, can prevent or delay end-stage kidney disease and hypothyroidism, enhances growth, and depletes cystine from muscle parenchyma; early and diligent treatment initiated promptly after diagnosis is associated with the best outcomes. Investigational approaches in this packet include a lentiviral gene therapy using autologous CD34+ cells transduced with CTNS cDNA (Novartis, DESIGNATED status only — not approved). Patient assistance programs may be available for eligible individuals, per this packet.

GeneReviews describes the natural history of nephropathic cystinosis as a progressive multi-organ disease in which cysteamine therapy substantially alters the clinical trajectory without providing a cure. Untreated nephropathic cystinosis leads to progressive renal failure; GeneReviews notes that early, optimal cystine-depleting therapy allows for a normal growth rate but does not produce catch-up growth, and that treated infants and toddlers typically maintain height in the 10th to 25th centile for age. Cystinosis accounts for approximately 5% of childhood kidney failure according to GeneReviews. Endocrine, ocular, musculoskeletal, and neurological complications accumulate over time across all organ systems documented in this packet. For the later-onset juvenile and non-nephropathic forms, renal involvement is absent or minimal, but corneal crystal accumulation and photophobia remain significant features. Prognosis is strongly influenced by the timing and adherence to cysteamine therapy.

Certified active trial records for cystinosis are present on ClinicalTrials.gov. This packet identifies 13 active trials (several), including a Phase 1 study of DFT383, a lentiviral gene therapy candidate developed by Novartis Pharmaceuticals targeting pediatric participants with nephropathic cystinosis (NCT06910813, start date June 2025); a study examining mitochondrial metabolism in cystinosis (NCT07319091, Hospices Civils de Lyon); a pharmacokinetics and pharmacodynamics study of NPI-001 and cysteamine bitartrate conducted by Nacuity Pharmaceuticals (NCT05994534); and the European Cystinosis Cohort natural history study (NCT05901077, INSERM). Active clinical trials for this condition are listed on ClinicalTrials.gov.