Cystinosis

Cystinosis is an autosomal recessive lysosomal storage disorder that presents with a proximal renal tubular damage also called Fanconi syndrome.

Classification

Occording to the age of onset, infantile, adolescent and adult forms can be distinguished. The predominant manifestation can be described as nephropathic or non-nephropathic (ocular).

Epidemiology

The estimated incidence of cystinosis is one in 100,000–200,000 live births. The incidence peaks 6 per 100,000 in Newfoundland, Canada.[Error: Macro 'ref' doesn't exist]

Clinical Findings

Kidney

The kidney manifestation of cystinosis can be summarized as Fanconi syndrome which includes proteinuria (predominantly low- molecular-weight), glucosuria, metabolic acidosis, hyperphospaturia. Furthermore wastage of water and salts including sodium, potassium, and calcium is observed. Finally the disorder develops into progressive renal failure.

Eye

The dominating ocular symptom is photophobia beause of cystein crystals accumulating in the cornea.

Other organs

Cystein deposits can damage other organs too. Endocrine glands, liver, pancreas, and pancreas can become dysfunctional.

Natural history

Most common is the infantile type which becomes apperent at 6-month of age after normal pregnancy and birth. The first symptoms are rather unspecific lack of appetite and a failure to thrive. Next water wastage and thurst is observed. Later photophobia is the first pathognomonic symptom. If not treated properly rickets and end-stage renal failure develop.

Pathogenesis

When proteins are catabolized in lyzosomes, cystin is normally carrieed by a transporter to the cytosol where it transformed to cysteine and reutilized for protein synthesis. If the transporter protein is deficient, cystin accumulates and because of its poor solubility crystalizes. Large cystin crystals impair cellular function in many organs.

Management

Cysteamine effectively can be applied to treat the disorder systemically and locally. Cysteamine binds cystin in Lysosomes allowing it to leave the organelle with the help of the lysin transporter. Corneal cystinosis can be treated with cysteamine eye drops.

Registry

CEMARA Cystinosis database

Systematic

Metabolic disturbances of proximal tubular function
	Cystinosis
		CTNS
	Dent disease
	Fanconi renotubular syndrome
	Fanconi-Bickel syndrome
	Fructose intolerance
	Galactosemia
	Glycogen storage disease 1
	Hepatorenal tyrosinemia
	Lowe disease
	MELAS syndrome
	Wilson disease