Cystinosis is a rare metabolic disease with an autosomal recessive inheritance. It is characterized by deposition of an extraordinary amount of cystine in different organs of the body, particularly the kidneys(1). In children, cystinosis is the most common cause of proximal renal tubular acidosis (RTA) as seen in Fanconi syndrome(2). Deposition of cystine may also occur in brain, bone, liver, lymph nodes, fibroblasts, leukocytes, cornea, conjunctiva, thyroid, pancreas and intestines(3). Depending on the degree of involvement, there are different types of cystinosis: infantile (nephropathic), adolescent (intermediate) and adult (benign) type(4). We present our experience with 10 cases of infantile cystinosis.

During 1995-2000, all children admitted with RTA at our center were investigated to find the cause. Patients with the following criteria were considered as cases of infantile cystinosis: (i) disease starting in the first two years of life, (ii)  ogically, (iv) growth retardation under third percentile, (v) presence of glucosuria with normoglycemia, (vi) history of consanguineous marriages, and (vii) presence of shining crystals of cystine seen in cornea using slit lamp microscopy.

Other diseases including isolated proximal RTA and distal RTA were ruled out. The patients were treated with polycitra, potassium chloride and Joulie’s solution. Activated vitamin D, dihydrotachysterol solution or Rocaltrol capsule were started at a dose 15-20 mg/kg and increased upto 40 mg/kg. Phosphocysteamine was started soon after the diagnosis was made at a dose of 10 mg/kg/day given in four divided doses and increased weekly up to 50 mg/kg/day (1.3 g/m2/day) over 4-6 weeks. The patients’ complicance was good and the drug complications were unremarkable.

Ten patients fulfilled our criteria of nephropathic cystinosis. All these children (6 girls and 4 boys) were the results of consanguineous marriages. Their mean age was 12 months (5-20 months). The time between the onset of symptoms to diagnosis was 3-12 months. The most frequent cause for admission was failure to thrive along with dehydration, acidosis and poor general condition. One patient was hospitalized with the diagnosis of nephrotic syndrome. The signs of failure to thrive and advanced rickets were seen in all the patients. Other features included polyuria and polydipsia in 70%, pathologic fracture in 20% and deafness in 10%. Laboratory findings included glucosuria in 10(100%), hyposthenuria (n=7), hypocalcemia(n=5), proteinuria (n=4), and azotemia(n=3). Two patients were documented to have associated hypothy-roidism, while one patient each had nephrolithiasis and severe anemia. Three infants died due to metabolic disturbances and a six year old died due to end stage renal failure. The remaining 6 children are doing well on treatment with phosphocysteamine. After starting treatment with this drug, patients showed marked increase in height and weight, fontanels started closing, teeth erupting and they started sitting, talking and walking. Two of these children with low thyroxine are on levothyroxine.

Nephropathic cystinosis is transmitted as an autosomal recessive trait with an incidence of 1 in 200000 live births(1,5). The actual defect is located at the levl of lysozomal transportation. The infantile or nephropathic cystinosis involves many organs and systems particularly kidneys which are the first to get involved leading to renal insufficiency. In adolescent type nephropathy is mild and renal involvement progresses very slowly(6). In the adult type renal involvement is not seen. Recently the disease is classified into two types: nephropathic cystinosis and non-nephropathic cystinosis. The nephropathic type is progressive, starting with symptoms between 6 and 18 months of age whereas non-nephropathic type is found in childhood at the age of 4-5 years and in adolescent 12-15 years(7). Nephropathic cystinosis becomes symptomatic at the age of 3-6 months with episodes of unexplained fever, vomiting, poor appetite and polyuria. At this stage inspite of tubular damage the glomerular filtration rate (GFR) is normal or midly inspired. It is only after the age of 5-6 years that there is renal insufficiency leading to chronic renal failure. In a retrospective study of 205 patients with hephropathic cystinosis, the mean time to renal death (serum creatinine > 8mg/dL) was 9.2 years(8).

The extra renal signs of cystinosis are numerous and are caused by intracellular accumulation of cystine in various organs, which continues even after renal replacement therapy(9). The most prominent features are rickets and growth retardation. Despite intensive supplementation with fluids, electrolytes, vitamins and calories, it is not possible to achieve a normal growth rate. Despite the many organ dysfunctions and the cerebral involvement, the intellectural, scholastic and social development of children with cystinosis is normal(10). The eyes are involved early extensively. Patchy retinal depigmentation, sparkling crystal in cornea and abundant crystals in the conjunctiva are observed, leading to photophobia and in some cases, to visual impairment(1). Hypothy-roidism is more common in these children and need treatment. The disease is treated in two ways, symptomatic like the other types of Fanconi syndrome and specific which attempts to remove or prevent the toxic accumulation of intracellular cystine from the various organs(11). In specific therapy, cysteamine or phosphocysteamine is given. The drugs help enter the lysozome and convert cystine into cysteine which is released from lysozome. FDA has advocated the use of these medicatios(12), starting with low dose of 10mg/kg/day. In our series all patients are the results of consanguinous marriages and therefore genetic counselling is very important.

Ctystinosis has also been reported from other parts of Iran, with similar clinical features(13-14). Most affected children are in families with history of parental consanguinity, highlighting the importance of genetic counselling.

Contributors: MM co-ordinated in drafting and will act as guarantor for the paper. AA and MBB collected data and drafted the manuscript. IM helped in counselling and BC helped in following up the cases.

Funding: None.

Competing interests: None stated.

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