POS-090 CYSTINOSIS: A RARE BUT TREATABLE CAUSE OF PROXIMAL RENAL TUBULAR ACIDOSIS

Abstract

Cystinosis is a rare lysosomal storage disorder which is characterized by defective cystine transporter and accumulation of cystine in lysosomes of cells of various body organs. Most common and severe presentation is in infancy as Fanconi syndrome (infantile nephropathic cystinosis). Incidence of cystinosis is 1 in 1 to 2 lakh newborns; with high incidence in Europe and UK. In India total 19 cases are registered with Cystinosis Society of India. The most common reported Indian mutation is p. Ser141Phe in contrast to 57Kb deletion affecting first 10 exons of CTNS which is commonly reported in Europe. We report a 23 months old male child of Indian origin, born out of non-consanguineous marriage, who presented with acute gastroenteritis and seizure. On examination, child had severe dehydration, pallor, signs of rickets, failure to thrive and polyuria even in the state of dehydration. Initial evaluation revealed a S. creatinine 2.62mg/dl. After fluid resuscitation renal functions improved (nadir S. creatinine 0.82mg/dl). As per mother the child had increased frequency of urination since age of 7 months with history of hospitalization twice for dehydration and dyselectrolytemia at the age of 8 months and 10 months. During follow up period, child had persistent hyperchloremic metabolic acidosis and low serum phosphate.Urine analysis revealed- proteinuria (2+, 100mg/dl), glycosuria (sugar 1+ , 100mg/dl) and phosphaturia. Urinary anion gap was positive; Urine chromatography was suggestive of generalized aminoaciduria. Ultrasound abdomen was normal. On the basis of above findings, the diagnosis of proximal renal tubular acidosis was made. Eye evaluation was suggestive of fine crystals deposition in cornea. In view of possibility of cystinosis, Genetic analysis by next generation sequencing was done which confirmed novel mutation in cystinosine gene (NM_001031681.2: c.771_793delGGGACCACGTGGCTGCAGT;p.Gly258SerfsTer30). Child was started treatment with cysteamine capsules and eyedrops along with bicarbonate, vitamin D, calcium and phosphorus supplements. On treatment child started gaining height and weight, urine output decreased and S. creatinine continued to be at nadir value of 0.8 mg/dl. Renal tubular acidosis may be just a clinical presentation of an underlying systemic disorder, therefore relevant clinical examination with need based molecular testing should be done. As early diagnosis forms the key to specific therapy for long term favorable outcome.