Cystinosis: a review

Abstract

Cystinosis is the most common hereditary cause of renal Fanconi syndrome in children. It is an autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene encoding for the carrier protein cystinosin, transporting cystine out of the lysosomal compartment. Defective cystinosin function leads to intra-lysosomal cystine accumulation in all body cells and organs. The kidneys are initially affected during the first year of life through proximal tubular damage followed by progressive glomerular damage and end stage renal failure during mid-childhood if not treated. Other affected organs include eyes, thyroid, pancreas, gonads, muscles and CNS. Leucocyte cystine assay is the cornerstone for both diagnosis and therapeutic monitoring of the disease. Several lines of treatment are available for cystinosis including the cystine depleting agent cysteamine, renal replacement therapy, hormonal therapy and others; however, no curative treatment is yet available. In the current review we will discuss the most important clinical features of the disease, advantages and disadvantages of the current diagnostic and therapeutic options and the main topics of future research in cystinosis.

Fig. 1

Schematic representation of the CTNS gene and all reported mutations in cystinosis patients. Exonic mutations are displayed in the lower half of the figure, while promoter and intronic mutations and large deletions are displayed in the upper half. INC: infantile nephropathic cystinosis, JNC: juvenile nephropathic cystinosis, OC: ocular cystinosis

Fig. 2

Typical growth charts in 2 cystinosis patients: a- Normal growth pattern at birth, followed by decreased growth velocity after six months. b- Progressive decrease in growth velocity in a patient who started cysteamine therapy after 2 years of age and was not treated with GH. Green and blue lines represent the 3rd and the 97th percentiles for Height and weight, respectively. (Adapted with permission from Besouw and Levtchenko, 2010) [27]

Fig. 3

Rickets in cystinosis. a- A cystinosis child with evident rachitic bone deformities. b- Active rachitic bone disease in X-Rays

Fig. 4

Corneal cystine crystals. Slit lamp examination of corneal cystine deposits (courtesy of Prof. Dr. Akmal Rizk, Dr. Mohamed Gamal and Prof. Dr. Neveen Soliman)

Fig. 5

The effect of cysteamine treatment in two siblings with nephropathic cystinosis. The growth in the 30-months old younger sibling (right side, 86 cm, 11.5 kg) who received pre-symptomatic cysteamine therapy at 3 months of age exceeded that of his 56-months old elder brother (left side, 80 cm, 10.5 kg) with later diagnosis and treatment at the age of 20 months (courtesy of Dr. Rasha Helmy and Prof. Dr. Neveen Soliman)