A Patient with Cystinosis Presenting Like Bartter Syndrome and Review of Literature
A 6-year old girl admitted to our hospital with severe growth failure, was referred to our clinic because hyponatremia (129 mmol/lt) and hypokalemia (2.1 mmol/lt). She had history of polyuria, polydipsia and episodes of dehydration requiring hospitalization. She was born full term. She was a low birth weight newborn. Her parents were 4th degree relatives and healthy. Motor and mental development stages were normal for her age. She had 3 siblings with no health problem. Two cousins of grandfather were being treated with diagnosis of ESRD one of whom died due to ESRD. In physical examination, both weight and height were below 3 percentiles for the age. She was normotensive (50p). She had blonde hair and fair skin. She had a triangular face and protuberant forehead. She was mildly dehydrated with dry mucosal surfaces and decreased skin turgor. Laboratory values: Hb 10.3 g/L, Hct 30.4%, WBC 7.700/mm3, PLT 229.000/mm3. Serum urea was high and creatinine was normal (56 mg/dl, 0,8 mg/dl, respectively). She had hyponatremia, hypokalemia, hypochloremia and hypophosphatemia (126mmol/lt, 2.9 mmol/lt, 88 mmol/lt, and 1.8 mg/dl respectively). Serum Mg (2.3 mg/dl), total protein (6.5 mg/dl), albumin levels (3.5 mg/dl), liver function and thyroid function tests were normal. Urine specific gravity was low (1000), urine pH was 5.5, and urinary glucose was negative. Urine microscopic examination was normal. Urine culture was negative. She had proteinuria (12 mg/m2/hour), and hypercalciuria (5.5 mg/kg/day). Fractional excretion of sodium and potassium was high (1.4% and 34%, respectively), tubular phosphate reabsorption was low (67%). In arterial blood gas analysis there was metabolic alkalosis (pH 7.45, cHCO3 28.3 mmol/L). Urinary aminoacid excretion was normal. Her daily urine volume was 2.5-4 lt/day (10 ml/kg/day) and fluid intake 5-6 lt/day. Glomerular filtration rate was 88 ml/min/1.73 m2. Plasma renin activity was 80ng/ml/h (0.5-5.9ng/ml/h), serum aldosterone level was 1400pg/ml (20-240pg/ml). Serum parathyroid hormone level was 1135pg/ml (11-67pg/ml). Urine B2 microglobulin was 13774µg/gr creatinin (≤300µg/gr creatinin). On renal ultrasonography (USG) examination there was no finding related to nephrocalcinosis and urinary system anatomy was normal. Renal biopsy has been performed during follow-up due to development of nephrotic range proteinuria, which revealed hyperplasia of juxtaglomerular apparatus.\nIn view of history of small gestational age birth, polyuria, polydipsia, failure to thrive, history of episodic dehydration, hypercalciuria, hypernatriuria, inability to concentrate urine, persistant hypokalemic hypochloremic metabolic alkalosis, normal blood pressure, elevated renin and aldosterone levels, and renal biopsy finding of hyperplasia at juxtaglomerular apparatus and parental consanguinity patient was thought to have Bartter syndrome. She received indomethacine and potassium chloride. During 6 months of follow-up, metabolic alkalosis and hypokalemia did not resolve, proteinuria increased and also her renal function deteriorated. When reevaluated, we detected increased glucose excretion in urine (24-hour glucose excretion was 5.2 gr/day). Radiologic examination of wrist, performed because of high level of serum alkaline phosphatase (774U/L), was compatible with rickets. As proximal tubulopathy findings were more predominant, rickets was detected, renal failure was settled and rare cases of cystinosis presenting with features of Bartter syndrome like metabolic alkalosis was described. In order to check for cystinosis presenting with metabolic alkalosis, slit lamp examination of the cornea revealed cystine crystals (). Leukocyte cystine levels were high (5.27 nmol 1/2 cystine/mg protein) and was compatible with homozygous cystinosis. We started to treat with oral cysteamine, cysteamine eye drops, 1,25 dihydroxycholecalciferol and oral potassium supplementation. At 12th month of follow-up now her alkalosis was converted to acidosis at last visit.