Contents
Introduction
Autosomal recessive (AR) lysosomal storage disorder caused by mutations in the CTNS gene encoding for the carrier protein cystinosin, transporting cystine out of the lysosomal compartment.
- M/C hereditary cause of renal Fanconi syndrome in children
History
Cystinosis was first described in literature in 1903 by the Swiss biochemist Emil Abderhalden (1877–1950) as the familial cystine accumulation disease. Abderhalden referred to a child initially encountered by Eduard Kaufmann, Basel, Switzerland (1860–1931). This patient died at the age of 21 months with massive cystine accumulation in multiple organs that were discovered at the postmortem examination. The Dutch pathologist George Lignac (1891–1954) was the first to provide a clear systematic description of the disease in 1924, and the first to associate cystinosis with its major clinical manifestations such as rickets, renal disease and growth retardation. This is why cystinosis was initially termed as the Abderhalden-Kaufmann-Lignac syndrome. Guido Fanconi (1892–1979), the Swiss pediatrician, also substantially contributed to the understanding of cystinosis by explaining the urinary substance losing nature of the disease. Hence, cystinosis was also recognized in the literature as the Lignac-Fanconi syndrome.
Pathophysiology
CTNS gene (17p13.2)
bi-allelic mutations
↓
Cystinosin
Lysosomal cystine-proton co-transporter
↓
Cystine
Accumulates in lysosomes of affected cells
&
Forms crystals in low lysosomal pH

Clinical features
Spectrum of disease:
- Infantile nephropathic cystinosis (M/severe, M/C 95% cases)
- Juvenile (late-onset) intermediate cystinosis
- Adult, non-nephropathic ocular cystinosis (L/severe)
Infantile nephropathic cystinosis:
Renal Fanconi syndrome
Asymptomatic aminoaciduria (initially) → Excessive urinary loss of amino acids, electrolytes, glucose and low molecular (LMW) to intermediate molecular weight (IMW) proteins
↓
Progressive loss of glomerular function
↓
End-stage renal failure
- At birth: Normal birth length & weight
- Infants:
- Failure to thrive, polyuria, polydipsia, episodes of severe dehydration and electrolyte imbalance, vomiting, constipation
- Vitamin D resistant rickets (rare)
Juvenile (late-onset) intermediate cystinosis:
- Variable spectrum of features: Ranging from isolated asymptomatic proteinuria, a mild renal Fanconi syndrome, to an overt nephrotic syndrome
- Slower progression rate to ESRD and extra-renal complications
- No remarkable growth retardation
Adult, non-nephropathic ocular cystinosis:
- Photophobia due to corneal cystine accumulation (rarely presents before adulthood)

Extrarenal manifestations:
- Corneal cystine accumulation + crystal formation → Photophobia & blepharospasm
- 1st extra-renal finding affecting all cystinosis patients
- Progressive cystine accumulation and crystal formation in thyroid follicular cells → Fibrosis & atrophy → Primary hypothyroidism (50-70% cases)
- Endocrine & exocrine pancreatic insufficiency (usually after renal allograft transplantation)
- 50% cases: By age 18 → Slow progressive loss of insulin secretion and C-peptide production → Glucose intolerance and diabetes mellitus
- Hepatomegaly ± splenomegaly (⅓ cases by 15 years)
- However, liver function usually remains unaffected
- Males: Primary hypogonadism (70 % cases)
- Central nervous system involvement
Diagnosis
Differential diagnosis
Differential diagnosis of renal Fanconi syndrome: other metabolic diseases:
- Tyrosinemia, galactosemia, glycogen storage diseases
- Wilson’s disease
- Dent’s disease
- Lowe’s syndrome
Management
Cystinosis is one of the few rare diseases having a specific treatment.

Aminothiol cysteamine (β-mercaptoethylamine)
- Deplete the intralysosomal cystine through the reduction of cystine, and the formation of cysteine and a cysteamine-cysteine mixed disulfide which exits the lysosome via the cationic amino acid transporter PQLC2, thus bypassing the original genetic and biochemical defects of the disease
