Masked hypertension delaying diagnosis in Gordon's syndrome

Abstract

ordon syndrome or familial hyperkalemic hyperG tension (MIM #145260) is a heterogeneous Mendelian syndrome. The hallmarks of this condition are arterial hypertension, hyperkalemia, normal anion gap metabolic acidosis, normal renal function and correction of the abnormalities by low doses of thiazide diuretics, which inhibit the Naþ-Cl cotransporter in the distal nephron [1]. In Gordon syndrome volume-dependent hypertension, hyperkalemia and metabolic acidosis are caused by an activated thiazide-sensitive Naþ-Cl cotransporter in the distal nephron. Mutations in either the WNK1 or the WNK4 kinase, two proteins that modulate the thiazidesensitive Naþ-Cl cotransporter, were disclosed approximately 10 years ago in some Gordon patients [2], but very recent data indicate that the condition often results from mutations in kelch-like 3 or cullin 3 [3]. We recently made the diagnosis of Gordon syndrome in a 25-year-old man with normal office blood pressure, who had been referred for diagnostic work up of lower limb muscle cramps and mild-to-moderate hyperkalemia. He was affected with chronic schizophrenia and on long-term medication with the antipsychotic drug olanzapine 10mg/day. Body weight was 76.8 kg, height 1.83 m, BMI 22.9 kg/m, blood pressure 120/85 mmHg or less, heart rate 70 beats per min and the clinical examination normal. The diagnostic work up disclosed normonatremia (141 mmol/l; reference: 135–145), hyperkalemia (7.1 mmol/l; reference: 3.5–5.0), acidosis (pH 7.29; reference: 7.38–7.42), hypobicarbonatemia (HCO3 19mmol/l; reference: 21–28), hyperchloremia (113 mmol/l; reference: 98–106), a lownormal uric acid level (201mmol/l; reference: 200–400), normal plasma creatinine (75mmol/l; reference: 106 or less), estimated glomerular filtration rate (111ml/min/ 1.73 m) and normal urinalysis and urinary calcium excretion (urinary calcium/creatinine ratio 0.16 mol/mol; reference: 0.32 or less). Plasma renin was normal (8.5 mU/l; reference: 1.8–9.6) and plasma aldosterone elevated (1.04 nmol/l; reference: 0.08–0.45). The presentation, with the exception of normal blood pressure, was considered consistent with the diagnosis of Gordon syndrome. Automated, intermittent, noninvasive ambulatory blood pressure monitoring over a 24-h period revealed both daytime (140/95 mmHg; min. 105/55 mmHg; max. 180/120mmHg) and night-time (130/80 mmHg; min. 110/70 mmHg; max. 160/110mmHg) arterial hypertension without nocturnal systolic dip, further supporting the suspected diagnosis of Gordon syndrome. Intermittent ambulatory blood pressure monitoring and blood potassium normalized on monotherapy with chlorthalidone 25mg/day (later 12.5 mg/day). Daytime blood