What is Nephropathic Cystinosis?
Nephropathic Cystinosis is a genetic disorder characterised by an accumulation of cystine in the lysosomes, resulting from defective transport of cystine across the lysosomal membrane into the cytoplasm. In cystinosis, free cystine accumulates throughout the body which leads to impaired cellular function in most organs, and notably in the kidney.
What causes Nephropathic Cystinosis?
Nephropathic Cystinosis is a hereditary metabolic disease, affecting gene (CTNS), located on the short arm of chromosome 17. It is transmitted by a recessive autosomal mechanism.
Nephropathic Cystinosis is a rare disease with an incidence estimated to be 1 case per 100,000 to 200,000 living births.
Clinical Presentation of Nephropathic Cystinosis
There are 3 clinical forms of Nephropathic Cystinosis, which differ with regard to the age of onset regard to the age of onset of the clinical signs and whether or not there is a renal involvement.
Cystinosis with nephropathy
• Infantile cystinosis (early-onset form) is the most frequent (95% of cases) and most severe form, which involves severe damage to the kidney, eye and other organs. It is the most common inherited cause of the renal Fanconi syndrome in children. The first clinical symptoms appear several months after birth (anorexia, vomiting, excessive thirst with polyuria, deterioration in growth rate and rickets). In the absence of treatment, the disease progresses to terminal renal failure between the age of 8 and 12 years old.
• Juvenile cystinosis (late-onset form) is a rare form. The clinical symptoms are comparable to those of the infantile form but of later onset, in adolescence or early adult life.
Cystinosis without nephropathy
• Adult or benign cystinosis is usually discovered fortuitously during an ophthalmologic examination revealing cystine deposits in the cornea and conjunctiva.
How to diagnose Nephropathic Cystinosis?
Biochemical signs of tubular disease
- in plasma: hyperchloraemic acidosis, hypophosphataemia, hypouricaemia
- in urine: glycosuria, proteinuria, hypercalciuria, hyperaminoaciduria, polyuria
Confirmation of diagnosis
- Elevated level of cystine in white blood cells
- Presence of cystine crystals in the cornea on slit-lamp examination
Determination of the White Blood Cell (WBC) cystine level is the key measurement for the diagnosis of nephropathic cystinosis and for monitoring the effectiveness of the treatment.
Treatment of Nephropathic Cystinosis?
Symptomatic
• Indomethacin to reduce the polyuria
• Fluids, electrolytes or other replacement molecules to compensate for the renal losses resulting from Fanconi’s’ syndrome
• Treatment of any extra-renal manifestations (growth hormone, insulin, tyrosine, etc.)
Specific treatment with cysteamine
• Allows cystine to be exported from the lysosomes
• Delays the development of renal failure when started early at the appropriate dose
Dialysis or kidney transplantation if renal failure develops
Cysteamine treatment should be continued even after dialysis or kidney transplantation as it may delay the subsequent complications secondary to cystine accumulation in extra-renal tissues. |
