Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder characterised by the build-up of cystine in various organs of the body resulting in progressive organ failure. Clinically, nephropathic cystinosis presents with renal tubular Fanconi syndrome between 6 and 12 months of age showing signs of fluid and electrolyte loss, aminoaciduria, glycosuria, phosphaturia, renal tubular acidosis, rickets and growth retardation. Untreated cases progress to end-stage renal failure in the first decade of life. A rare late-onset form of cystinosis presents in older children that causes renal impairment but not necessarily Fanconi syndrome. Adults with 'benign' cystinosis have asymptotic corneal cystine deposition but do not have progressive renal damage.
The diagnosis of nephropathic cystinosis can be confirmed by slit lamp examination of the cornea which reveals needle-shaped tinsel-like refractive opacities. The levels of cystine can be measured in bone-marrow cells, leukocytes, and cells of the rectal mucosa.
Mutations in CTNS gene, which encodes cystinosin is associated with nephropathic cystinosis.
Shahkarami et al. (2013) studied 21 patients of Arab origin in Iran with nephropathic cystinosis. All except two of these patients were products of consanguineous unions. All patients showed growth retardation and the presence of cystine crystal in the cornea. Other common clinical features included rickets and polyuria-polydispia. All patients were glucosuric. Other common biochemical features included renal tubular acidosis, proteinuria, and hyposthenuria.
Soliman et al. (2009) screened 33 patients from 24 Egyptian families for nephropathic cystinosis. Patients were suspected on the basis of presentation with proximal renal tubular acidosis and/or hypophosphatemic rickets, and chronic kidney disease, particularly in families reporting death of siblings due to a similar condition. In addition, siblings of index cases were also screened. Slit lamp examination for corneal cystine crystals was used to screen children above two years of age and WBC cystine assay was used to confirm the diagnosis in children below 2 years of age. Cystinosis was confirmed in 16 patients from 15 families. Diagnosed patients included eight boys and eight girls with a mean age at diagnosis of 52.7 ± 39.2 months (10-112 months). Parents were consanguineous in 12 families (80%) and sibling deaths were reported in six families (40%). Soliman et al. (2009) suggest that slit lamp examination is a simple and reasonably sensitive method for diagnosis of nephropathic cystinosis above 2 years.
Macias-Vidal et al. (2009) analyzed the CTNS gene in 32 unrelated cystinosis patients, 27 Spanish and five Moroccan, and identified homozygous or compound heterozygous mutations in 28 of them. All but two of the patients had the infantile form of cystinosis and had truncating mutations or mutations affecting conserved amino acids associated with transmembrane regions of the protein.
Abou-Chaaban et al. (1997) studied the pattern of pediatric renal diseases among children in the Dubai Emirate during the period from 1991 to 1996. In this period, a total of 712 pediatric patients were seen with various renal problems. Abou-Chaaban et al. (1977) observed five Palestinian patients with cystinosis with renal involvement. All these patients developed chronic renal failure. Abou-Chaaban et al. (1997) noted that children of Palestinian origin had the highest prevalence of cystinosis and that all affected children had consanguineous parents.
[Abou-Chaaban M, Al Murbatty B, Abdul Majid M. Spectrum of pediatric renal diseases in Dubai. Saudi J Kidney Dis Transplant. 1997; 8(3):310-3.]
Aldahmesh et al. (2009) reported the clinical and molecular characteristics of 21 patients from 13 apparently unrelated Saudi families with cystinosis. All patients presented with growth retardation in infancy secondary to renal failure. In addition, all of them manifested Fanconi renal syndrome. Ocular manifestations included intracorneal accumulation of crystalline deposits, conjunctival as well as iris deposits, and an absence of cataract.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Lysosomal storage disorders were the most diagnosed category of IEM in this cohort (74 out of 248 cases, 30%). Among them, one case was found to have cystinosis with an estimated incidence of 1 per 100,000 live births. All cases of lysosomal storage disorders were confirmed by enzyme assay on skin fibroblasts, liver biopsy or leukocytes. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.
Abou-Chaaban et al. (1997) studied the pattern of pediatric renal diseases among children in the Dubai Emirate during the period from 1991 to 1996. In this period, a total of 712 pediatric patients, including 230 nationals of the United Arab Emirates, were seen with various renal problems. Abou-Chaaban et al. (1977) observed two Emirati patients with cystinosis with renal involvement. All these patients developed chronic renal failure. The patients either expired or underwent cadaveric kidney transplantation [Abou-Chaaban M, Al Murbatty B, Abdul Majid M. Spectrum of pediatric renal diseases in Dubai. Saudi J Kidney Dis Transplant. 1997; 8(3):310-3].
Al-Jasmi et al. (2013) studied the prevalence of lysosomal storage diseases (LSDs) in the UAE and reported their mutation spectrum. This study included all the patients diagnosed and followed up between 1995 and 2010 at the only two metabolic referral centers in the country. In this period, a total of 119 patients, 65 of them Emiratis, were diagnosed with LSDs. One Emirati patient with Cystinosis was identified in this study, giving a birth prevalence of 0.25 per 100,000 for Emiratis. The patient presented with an infantile onset of the disease and was treated early. He showed a normal growth, although he had learning difficulties.