Recurrent paralysis in a young man P A Koul, A Wahid CASE REPORT 1612 THE LANCET • Vol 355 • May 6, 2000 Case report A 22-year-old man presented in July, 1997, with 1 day history of weakness of both legs that progressed to involve his arms over a few hours. He was breathless, with no sensory abnormalities or sphincter involvement. He had had more than 200 similar episodes of weakness over the past 9 years, requiring multiple admissions. He had hypokalaemia during at least five admissions. He was diagnosed with hypokalaemic periodic paralysis (HOPP). Every time he became weak he would treat himself with potassium chloride, and the weakness would respond. He denied any precipitating factors. Previously he had been given acetazolamide, but he stopped taking this drug because it increased episodes of weakness. On examination he was drowsy, irritable, cyanosed, with grade 2 motor quadriparesis. Respiratory rate was 56/min with chest expansion of 0·5 cm. There were no signs of meningeal irritation or cranial nerve, sensory, cortical, or sphincter involvement. Full blood count was normal. The serum sodium was 136 mmol/L, potassium 1·8 mmol/L, chloride 112 mmol/L, and bicarbonate 9·2 mmol/L. Arterial blood gas analysis showed pH 7·26, a PaO 2 of 23·3 mm Hg with an O 2 saturation of 76·9%. Urine pH was 7·0, dipstick was negative for protein and glucose and microscopy was normal. The serum concentrations of urea, creatinine, glucose, uric acid, calcium, phosphate, liver function tests, creatinine kinase, and lactose dehydrogenase were normal. The patient was ventilated and potassium chloride and sodium bicarbonate were given. He had a rapid recovery over the next 24 hours. Urine pH remained alkaline. 24-hour excretion of phosphate, uric acid, and calcium was normal. There was no aminoaciduria or glycosuria. Urinary sodium was 43·2 mmol/L, potassium 32·6 mmol/L, chloride 69 mmol/L. Fractional excretion of bicarbonate at induced serum bicarbonate of 21·2 mmol/L (after a bicar- bonate infusion) was 3·2% and U-B pCO 2 11·2 mm Hg. Serum and urinary osmolality were normal. Radiographs of the chest, and bones showed osteopenia. Electrocardio- gram showed U waves initially which became normal after correction of serum potassium. Radiological examination of the kidneys were normal. Viral serology was negative. Thyroid function was normal. Nerve conduction studies were normal. Electromyography showed a diminution of interference pattern. The patient was discharged on oral sodium bicarbonate and potassium chloride, when his pH was 7·34 with bicarbonate of 19·2 mmol/L. Over the next 2 years, he had only two episodes of weakness, each brought about by discontinuation of the therapy, and both responded to reinstitution of potassium chloride and bicarbonate. A screen of the family members was negative for any acidification defect. Lancet 2000; 355: 1612 Department of Internal Medicine, Sherikashmir Institute of Medical Science, Soura, Postbag 27, Srinagar 19011, Kashmir, India (P A Koul MD, A Wahid MD) Correspondence to: Dr Koul (e-mail: parvaizk@hotmail.com) Hypokalaemic periodic paralysis classically presents in its familial form, but occasionally occurs as a result of excessive gastrointestinal or urinary loss of potassium. Distal renal tubular acidosis (RTA) as here results in an inappropriately high potassium excretion causing symptomatic hypokalaemia. The disorder is endemic in Thailand, 1 but has been reported from many other countries in sporadic, 2 or hereditary forms. Classic distal RTA is characterised by hyperchloraemic metabolic acidosis and a defect in urinary acidification, which may be associated with hypercalciuria, hypocitraturia, nephro- lithiasis, nephrocalcinosis, hypokalaemia, progressive renal failure, and growth retardation. 3 Hypokalaemic muscular weakness is a major feature, typically involveing limb muscles in a motor, no-reflexes manner. 1 The acquired and inherited forms of dRTA all impair distal acidification and net acid secretion. Defects in the H+ secretion by the distal nephron could arise as a abnormality of the H+-ATPase, H+ K+ ATPase, the HCO3-/C1- exchanger, in the cytoplasmic fraction of the carbonic anhydrase (CAII). 3 A defect in the chloride- bicarbonate exchanger gene AE1 (SCL4A1) occurs in auto- somal dominant dRTA. 4 Mutations in the ATPB1 en- coding the B-subunit of apical proton pump H+-ATPase mediating distal nephron secretion occur in autosomal recessive dRTA associated with sensorineural hearing loss. Familial HOPP is an autosomal dominant disorder of muscle with episodes of weakness in association with a reduction in serum potassium. The episodes begin in adolescence and often wane by the fifth or sixth decades of life, although patients can have a late-onset chronic proximal weakness with myopathic changes. 5 Abnormalities of voltage gated calcium channel, one of the key regulators of intracellular calcium concentration, have been implicated in HOPP. The human HOPP gene maps to chromosome 1q31–32. An abnormal K+-ATP channel has been shown in some patients with HOPP. Altered calcium ion homoeostasis has been implicated in forcing the K+-ATP channels into subconductance states, irreversibly modifying the channel gating. In patients with HOPP, it has been proposed that as a result of the low basal activity of the K+-ATP channels, no efflux of K+ ions occurs. This mechanism can explain the hypokalaemia, depolarisation of the fibres and paralysis following insulin administration in cases of HOPP. Doctors in the emergency room should be aware of the diagnosis of dRTA, shown by an alkaline urine and low ammonium excretion during hyperchloraemic acidosis. The diagnosis is important because acetazolamide which has been used to prevent the recurrences of HOPP may in RTA have disastrous consequences causing further acidosis and hypokalaemia. Bicarbonate therapy leads to a prompt response and prevents subsequent episodes. References 1 Nimmannit S, Malasit P, Susaenger W, et al. Prevalence of endemic distal renal tubular acidosis in the northeast of Thailand. Nephron 1996; 72: 604–10. 2 Koul PA, Saleem SM, Bhat D. Sporadic distal renal tubular acidosis and periodic hypokalemic paralysis in Kashmir. J Intern Med 1993; 233: 463–66. 3 Dubose TD Jr, Alpern RJ. Renal tubular acidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Basis of Inherited Disease. New York, NY: McGraw-Hill, 1995: 3655–89. 4 Jarolim P, Shayakul C, Prabakaran D, et al. Autosomal dominant distal renal tubular acidosis is associated in three families with heterozygosity for the R529H mutation in the AE1 (band 3) C1-/HCO3-exchanger. J Biol Chem 1998; 273: 6380–88. 5 Lehmann-Horn F, Rudel R. Molecular pathophysiology of the voltage- gated ion channels. Rev Physiol Biochem Pharmacol 1996; 128: 195–208.