cystinosis

Cystinosis, also known as Abderhalden Kaufmann Lignac syndrome, is the most common hereditary cause of renal Fanconi syndrome. Cystinosis is one of the lysosomal storage disorders.

Epidemiology

It has a reported incidence of 1:192,000 . Cystinosis is typically diagnosed in infancy.

Clinical presentation

Cystinosis typically presents with failure to thrive and a Fanconi syndrome in early infancy. Progressive multi-organ involvement develops over the first few decades of life.

• renal manifestations
  • Fanconi syndrome
    • failure of renal tubular solute and water resorption leading to excess urinary solute excretion and a type 2 renal tubular acidosis
  • progressive renal failure by 10 years of age
  • calciuria leading to increased risk of renal calculi and osteomalacia
• extra-renal manifestations
  • ocular 
    • photophobia, blepharospasm from corneal involvement
  • neuromuscular
    • distal vacuolar myopathy presenting as progressive distal muscle wasting and weakness
  • central nervous system
    • hypotonia, speech delay, motor impairment, cognitive dysfunction have been described
  • endocrine
    • primary hypothyroidism
    • pancreatic exocrine failure causing clinical diabetes mellitus by the age of 18 years in 50% of patients
    • primary hypogonadism in males
  • skin
    • hypopigmentation, coarsened facial features, impaired sweating have been described

There are three main clinical phenotypes:

• infantile form (95%)
  • most severe with early-onset renal failure
• juvenile-onset form (5%)
  • slower onset to renal failure and milder degrees of Fanconi syndrome
• adult form (case reports)
  • corneal involvement with renal sparing

Pathology

Cystinosis is caused by a mutation of the CTNS gene, which is inherited in an autosomal recessive inheritance pattern. This gene encodes cystinosin, a transporter that carries cystine from lysosomes into the cytoplasm. A defect in the CTNS gene causes an accumulation of cystine in lysosomes, leading to cystine crystallization and resultant lysosomal dysfunction . Lysosomal dysfunction in cystinosis manifests across a variety of organ systems, most prominently in the renal system.

Radiographic features

Imaging features are non-specific and may include:

• rickets
• renal medullary nephrocalcinosis
• nephrolithiasis

Treatment and prognosis

The mainstay of treatment is cystine-depleting therapy with cysteamine. With modern medical therapy, life expectancy can extend past 50 years.

History and etymology

Initially described by Swiss biochemist Emil Abderhalden (1877-1950) .