sodium-bicarbonate and Elliptocytosis--Hereditary

A 39-year old man had periodic paralysis due to hypokalaemia. Investigations led to the diagnosis of distal renal tubular acidosis (dRTA) and Southeast Asian ovalocytosis (SAO). Both can originate in mutations of the anion-exchanger 1 gene (AE1), which codes for band 3, the bicarbonate/chloride exchanger in both the red cell membrane and the basolateral membrane of the collecting tubule alpha-intercalated cell. The finding of diffuse osteosclerosis led to the suspicion of coexisting fluorosis.

Topics: Acidosis, Renal Tubular; Administration, Oral; Adult; Bone Density Conservation Agents; Calcium, Dietary; Elliptocytosis, Hereditary; Fluoride Poisoning; Fluorosis, Dental; Humans; Male; Osteosclerosis; Potassium Chloride; Quadriplegia; Sodium Bicarbonate

Southeast Asian ovalocytosis (SAO) is the best-documented disease in which mutation in the anion exchanger-1 (AE1) causes decreased anion (chloride [Cl-]/bicarbonate [HCO3-]) transport. Because AE1 is also found in the basolateral membrane of type A intercalated cells of the kidney, distal renal tubular acidosis (dRTA) might develop if the function of AE1 is critical for the net excretion of acid. Studies were performed in a 33-year-old woman with SAO who presented with proximal muscle weakness, hypokalemia (potassium, 2.7 mmol/L), a normal anion gap type of metabolic acidosis (venous plasma pH, 7. 32; bicarbonate, 17 mmol/L; anion gap, 11 mEq/L), and a low rate of ammonium (NH4+) excretion in the face of metabolic acidosis (26 micromol/min). However, the capacity to produce NH4+ did not appear to be low because during a furosemide-induced diuresis, NH4+ excretion increased almost threefold to a near-normal value (75 micromol/L/min). Nevertheless, her minimum urine pH (6.3) did not decrease appreciably with this diuresis. The basis of the renal acidification defect was most likely a low distal H+ secretion rate, the result of an alkalinized type A intercalated cell in the distal nephron. Unexpectedly, when her urine pH increased to 7.7 after sodium bicarbonate administration, her urine minus blood carbon dioxide tension difference (U-B Pco2) was 27 mm Hg. We speculate that the increase in U-B Pco2 might arise from a misdirection of AE1 to the apical membrane of type A intercalated cells.

Topics: Acidosis, Renal Tubular; Adult; Antiporters; Carbon Dioxide; Diuretics; Elliptocytosis, Hereditary; Female; Furosemide; Humans; Hydrogen-Ion Concentration; Quaternary Ammonium Compounds; Sodium Bicarbonate