Family paralysis

Abstract

In October, 2009, a 16-year-old Chinese boy presented to an emergency department with muscle paralysis of the legs. He denied diuretic use but reported occasional tetany since childhood. His mother had a history of hypokalaemia. His blood pressure was 120/70 mm Hg, and heart rate 56 beats/min. He had symmetric flaccid paralysis with areflexia in both legs. Blood biochemistry showed osmolality 291 mmol/kg water, sodium 139 mmol/L, potassium 1·6 mmol/L, chloride 97 mmol/L, carbon dioxide 28·8%, magnesium 0·52 mmol/L, urea 6 mmol/L, and creatinine 0·07 mmol/L. Electrocardiogram showed prominent U waves. Thyroid function was normal. Spot urine studies showed urine osmolality 321 mmol/kg water, sodium 71 mmol/L, potassium 12 mmol/L, chloride 68 mmol/L, calcium 0·4 mmol/L, magnesium 3·2 mmol/L, and creatinine 5·1 mmol/L. His transtubular potassium gradient was high at 7 (normal <3), indicative of renal potassium wasting. The findings of high urine sodium and chloride concentrations, hypomagnesaemia with high fractional excretion of magnesium (3·6%; normal <1%), and hypocalciuria (urine molar calcium to creatinine ratio 0·01; normal 0·20–0·30) led to the diagnosis of Gitelman's syndrome, a defect in the thiazide-sensitive sodium/chloride cotransporter (NCC) on the apical membrane of distal convoluted tubule. Sequencing of the SLC12A3 gene encoding the NCC in his family showed that our patient had compound heterozygous mutations (T163M from father and T649M from mother). His mother, who had asymptomatic hypokalaemia (2·7 mmol/L), hypomagnesaemia (0·54 mmol/L), and hypocalciuria, carried another novel mutation (E688frameshift) on the second allele (figure).