ABSTRACT
Aims: To screen cases of infantile cystinosis among different forms of proximal renal tubular acidosis (RTA). Study Design: Cross sectional. Place and Duration of Study: From a total of 25 families of RTA followed up in Nephrology unit of Mansoura University Children's Hospital (MUCH), Egypt, two unrelated families were diagnosed as infantile nephropathic cystinosis using clinical suspicion plus mutation analysis of CTNS gene in the period between January 2008 and November 2012. Methodology: Two families with multiple cases of infantile nephropathic cystinosis have been diagnosed. In absence of high-performance liquid chromatography and tandem mass spectrometry used for measuring intraleucocyte cystine, diagnostic tools for cystinosis used in the current work were clinical and laboratory evidences of PRTA, slit lamp detection of corneal cystine crystals and finally identification of CTNS gene mutations. All patients were subjected to routine echocardiography because of accidental discovery of heart malformation in one case. Rare mutant variant of the first family was subjected to RNA analysis which unfortunately failed, alternatively an in silico study was used to predict splice site. Results: All patients with cystinosis manifested a severe clinical course. Proband of family 1 showed two known mutations; deletion in the exon 3 (c.18_21 del GACT) and substitution in acceptor splice site of intron 11 (c.971 -12G>A). In silico study predicted an anticipated splice site that modified the open reading frame in carboxy-terminal region. Probands of family 2 were affected by ventricular and atrial septal defects in younger, and mild mitral and aortic incompetence in older patient; their DNA analysis revealed a novel nonsense mutation (c.734 G>A) which caused a premature stop codon in position 245 of protein. Conclusion: Nephropathic cystinosis has been diagnosed with ease in Egyptian population without need of sophisticated investigations. A novel mutation had been added to the list of CTNS gene variants.