There are different types of cystinosis: the nephropathic and non-nephropathic. The nephropathic type has renal and extra renal manifestations. This can present in an infantile or late onset form. The infantile form is the most severe and, if left untreated, can lead to end stage renal disease by late childhood. The nonnephropathic type presents with photophobia and only corneal cystine crystals without renal or systemic involvement. This type is also called ocular cystinosis.
Children with the infantile form appear normal at birth. The clinical picture becomes apparent between 3 and 6 months of age. The most common renal manifestation is the renal Fanconi syndrome due to renal proximal tubular dysfunction. This classically presents with failure to thrive, polyuria up to 2–3 litres/day, polydipsia, constipation, dehydration, weakness and hypophosphatemic rickets. Patients will also have glucosuria, proteinuria, phosphaturia, aminoaciduria and metabolic acidosis.
Our patient presented at the age of 7 months with failure to thrive and had the classic features of renal Fanconi syndrome such as polyuria, polydipsia and constipation. She also had signs of rickets clinically, biochemically and radiologically. The laboratory investigations were also classic for renal Fanconi syndrome: normal anion gap, metabolic acidosis with hypokalemia and hypophosphatemia. She also had evidence of renal wasting of glucose which was suggested by normal serum glucose and a positive dipstick for glucose. The protein to creatinine ratio was quite elevated despite normal albumin and minimal proteinuria on dipstick. This suggests that the proteins lost are low molecular weight amino acids rather than the albumin which is a large molecular weight protein. She also had evidence of renal phosphate wasting suggested by hypophosphatemia and low tubular reabsorption of phosphate which was 55% (less than 85% indicates renal wasting).
The other manifestations of nephropathic cystinosis are extrarenal and present later on. These include myopathy and dysphagia due to accumulation of cystine in the muscles, endocrine involvement such as hypothyroidism and diabetes mellitus, hepatomegaly, hypersplenism and photophobia from the corneal accumulation of cystine in the cornea. Fundoscopy may show depigmentaion of the retina. Retinal changes may appear before the corneal features. The corneal crystals require slit lamp examination. These crystals are not present at birth; they appear between 16 and 20 months of age,1
The corneal crystals are virtually pathognomonic. However, their absence does not exclude the diagnosis of cystinosis. Our patient had the typical crystal deposits in the cornea as seen in .
Nephropathic cystinosis is the most common cause of renal Fanconi syndrome in the Caucasian population. This disease is quite rare in the Middle East. Only three Middle Eastern countries, Egypt, Saudi Arabia and Iran, have reported this disease in their populations.3
These studies have provided a lot of important information on nephropathic cystinosis in the region. Soliman et al
., in the Egyptian study, were able to identify 16 patients with nephropathic cystinosis out of 33 who presented with Fanconi syndrome to a single centre.3
The Saudi study, by Aldahmesh et al.
, identified 8 mutations, 4 of which were novel, in 21 patients with nephropathic cystinosis of Arab origin.5
The Iranian study by Mirdehghan et al
. described the clinical features of patients with nephropathic cystinosis presenting over a five year period to a single centre.4
The diagnosis of nephropathic cystinosis in this case was based on the presence of corneal cystine crystals in an infant with Fanconi syndrome. Traditionally, white blood cell cystine assay was the test of choice to confirm the diagnosis. This test is not available in Oman and it is costly and technically difficult to perform; there are only a few laboratories worldwide that can perform it. Currently, genetic testing by mutation analysis of the CTNS gene is a better alternative to confirm the diagnosis. It is necessary to consider sending samples to a specialised laboratory in case the diagnosis of nephropathic cystinosis is suspected in an infant younger than 20 months where the cystine crystals might not be present. Early treatment with cysteamine which is a cystine depleting agent can delay the progression to end stage renal disease.