BACKGROUND

This study was conducted to investigate CTNS (cystinosin, lysosomal cystine transporter) gene mutations and the clinical spectrum of nephropathic cystinosis among patients diagnosed with the disease in a single center in Turkey.

METHODS

Patients' clinical and laboratory data were extracted from an electronic health registry. Molecular CTNS gene analysis was performed using either next-generation sequencing or Sanger sequencing.

RESULTS

Eleven patients (age range: 1.5-12 years) from nine families were identified. The presenting complaint was growth retardation in seven patients; polydipsia and polyuria in three patients; and vomiting in two patients. At presentation, electrolyte loss was noted in all patients, of which eight patients presented with metabolic acidosis, and three patients presented with metabolic alkalosis. All patients also presented with proteinuria and glucosuria, and four patients developed varying degrees of renal insufficiency, for which peritoneal dialysis was initiated in one patient. Cystine crystals were detected via ocular examination in one patient at presentation. No cystine crystals were detected among patients who underwent bone marrow aspiration. In the CTNS gene, a p.T7FX7 (c.18-21del4bp) mutation was detected in three patients, whereas a p.E227E (c.681 G>A) (homozygous) mutation was detected in eight patients.

CONCLUSIONS

We detected two distinct mutations, p.T7FX7 (c.18-21del4bp) and p.E227E (c.681 G>A) (homozygous), in the CTNS gene in 11 patients with cystinosis from the East Anatolian region of Turkey. Patients with a homozygous c.681 G>A (p.E227E) mutation are more likely to develop chronic renal failure and should be monitored closely, whereas patients with a p.T7FX7 (c.18-21del4bp) mutation have a milder phenotype. Additionally, metabolic alkalosis does not exclude cystinosis, although cystinosis is a cause of proximal renal tubular acidosis.