Ref
CACNA1S / R528G / NS / KCL / Aborted attacks of paralysis / e1
CACNA1S / R528G / 1 / Acetazolamide 250mg b.d + potassium salts
Combination of spirinolactone 25mg b.d, amiloride 5mg b.d and potassium salts / No response to acetazolamide
Combination of diuretics and potassium reduced frequency and severity of attacks / e2
CACNA1S / R528H / 1 / Low carbohydrate diet, potassium 40meq od and acetazolamide 250mg tds. / Reduced frequency and severity of attacks. / e3
CACNA1S / R528H / 4
(1 kindred) / Acetazolamide discontinued for a trial of verapamil versus placebo. / Baseline response to acetazolamide not reported. Two patients reported significant improvement with verapamil, and two no response. / e4
CACNA1S / R528H / 5
(3 kindreds) / Dietary modification(3pts) OR Acetazolamide(1pt) OR Spirinolactone(1pt) / All patients attack free following treatment / e5
CACNA1S / R528H / 8 / Acetazolamide / Beneficial for 5 pts
No effect on symptoms for 3 pts / e6
CACNA1S / R528H / 1 / Acetazolamide, Spirinolactone, Potassium Aspartate and Potassium Chloride / Little effect on symptoms from any of the listed medications. / e7
CACNA1S / R528H / NS / Acetazolamide / Beneficial for most pts treated.
One reported worsening of symptoms / e8
CACNA1S / R528H / 5
(no of kindreds NS) / Acetazolamide / Beneficial for 2 pts
No effect for 3 pts / e9
CACNA1S / R1239H / 5
(1 kindred) / Acetazolamide and potassium supplements continued in 4/5 pts consenting to a trial of verapamil versus placebo / Baseline response to acetazolamide not reported but no additional response to verapamil experienced. / e4
CACNA1S / R1239H / 13 / Acetazolamide / Beneficial for 8 pts
No effect on symptoms for 4 pts
Deleterious effect on symptoms for 1 pt / e6
CACNA1S / R1239H / 4
(1 kindred) / KCL and Acetazolamide / Beneficial for 3 pts.
No effect for 1 pt but medication taken irregularly / e10
CACNA1S / R1239H / NS / Acetazolamide / Beneficial effect for most pts treated / e8
CACNA1S / R1239H / 1 / Acetazolamide / No effect / e9
CACNA1S / R1239G / 1 / Spirinolactone 25mg bd / Improved symptoms
Note: 2 clinically affected cousins reported no effect with ACZ treatment but an improvement with spirinolactone. Genetic analysis was not performed on these 2 pts. / e11
CACNA1S / R1239G / 3
(1 kindred) / Acetazolamide OR a
combination of spirinolactone, amiloride and potassium supplements / No effect of ACZ for 2 pts
Deleterious effect of ACZ for 1 pt but then treated successfully with a combination of diuretics and potassium supplements / e9
CACNA1S / R897S / 1 / Potassium supplements 2-3mmol/kg/day and acetazolamide 5-10mg/kg/day / Treated from age 2-6years. Frequency and severity of attacks reduced but duration of attacks increased. / e12
SCN4A / “Sodium channel mutations” NO / 4 / Acetazolamide / Deleterious effect / e8
SCN4A / R669H / 2 / Pt 1:
Dietary regime, potassium supplements and a carbonic anhydrase inhibitor (not specified) / Reduced frequency of attacks / e13
Pt 2:
acetazolamide 250mg bd / Attack free for 2 months then one severe attack responding to potassium infusion. No long-term response documented
SCN4A / R669H / 1 / Acetazolamide / No response / e9
SCN4A / R669H / 1 / Potassium supplements / No attacks during 12 month follow up period / e14
SCN4A / R672G / 3
(1 kindred) / Acetazolamide / Deleterious effect / e6
SCN4A / R672G / 1 / Acetazolamide OR
Combination of spirinolactone, amiloride and potassium supplements / Deleterious effect of ACZ but then treated successfully with a combination of diuretics and potassium supplements / e9
SCN4A / R672C / NS / Either acetazolamide 500mg a day OR dichlorphenamide 100mg a day / Attack free for at least 6 months on average / e15
SCN4A / R672C / 1 / Acetazolamide / No response
SCN4A / R672S / 3
(1 kindred) / acetazolamide
triamterene / Severe quadriparesis within 12 - 60 hours of acetazolamide.
Reduction in frequency and severity of attacks with Triamterene / e16
SCN4A / R672S / 1 / Acetazolamide 250mg bd and spirinolactone 100mg per day / Reduced frequency of attacks / e17
SCN4A / R672S / 1 / Acetazolamide 250mg per day and potassium taken at onset of attack or before strenuos exercise / Reduced frequency of attacks / e18
SCN4A / R675G / 5
(1 kindred) / Acetazolamide 250mg per day / 1 pt no response to 10 years continuos treatment
4 pts reported a reduced duration of attacks with intermittent ACZ treatment / e19
SCN4A / R675Q / 2
(2 kindreds) / Acetazolamide 500mg per day / Pt 1: no benefit
Pt 2: attack free since taking ACZ (length of treatment not documented) / e19
SCN4A / R675W / 1 / Acetazolamide 250mg per day / Reduced frequency and severity of attacks / e19
SCN4A / R1132Q / 1 / Acetazolamide
Potassium peri-attack / No response to acetazolamide
Potassium ingestion reduced duration of attack / e20
Table e-1
e-References
(e1) Wang Q, Liu M, Xu C, et al. Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family. J Mol Med 2005;83(3):203-208.
(e2) Kil TH, Kim JB. Severe respiratory phenotype caused by a de novo Arg528Gly mutation in the CACNA1S gene in a patient with hypokalemic periodic paralysis. Eur J Paediatr Neurol 2010;14(3):278-281.
(e3) Hecht ML, Valtysson B, Hogan K. Spinal anesthesia for a patient with a calcium channel mutation causing hypokalemic periodic paralysis. Anesth Analg 1997;84(2):461-464.
(e4) Links TP, Arnoldus EP, Wintzen AR, van der HJ, Gerritsen JJ, Brandenburg HC. The calcium channel blocker verapamil in hypokalemic periodic paralysis. Muscle Nerve 1998;21(11):1564-1565.
(e5) Kim SH, Kim UK, Chae JJ, et al. Identification of mutations including de novo mutations in Korean patients with hypokalaemic periodic paralysis. Nephrol Dial Transplant 2001;16(5):939-944.
(e6) Sternberg D, Maisonobe T, Jurkat-Rott K, et al. Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 2001;124(Pt 6):1091-1099.
(e7) Kawamura S, Ikeda Y, Tomita K, Watanabe N, Seki K. A family of hypokalemic periodic paralysis with CACNA1S gene mutation showing incomplete penetrance in women. Intern Med 2004;43(3):218-222.
(e8) Miller TM, as da Silva MR, Miller HA, et al. Correlating phenotype and genotype in the periodic paralyses. Neurology 2004;63(9):1647-1655.
(e9) Kim JB, Kim MH, Lee SJ, Kim DJ, Lee BC. The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis. J Korean Med Sci 2007;22(6):946-951.
(e10) Kusumi M, Kumada H, Adachi Y, Nakashima K. Muscle weakness in a Japanese family of Arg1239His mutation hypokalemic periodic paralysis. Psychiatry Clin Neurosci 2001;55(5):539-541.
(e11) Kim JB, Lee KY, Hur JK. A Korean family of hypokalemic periodic paralysis with mutation in a voltage-gated calcium channel (R1239G). J Korean Med Sci 2005;20(1):162-165.
(e12) Chabrier S, Monnier N, Lunardi J. Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene. J Med Genet 2008;45(10):686-688.
(e13) Bulman DE, Scoggan KA, van O, et al. A novel sodium channel mutation in a family with hypokalemic periodic paralysis. Neurology 1999;53(9):1932-1936.
(e14) Maffe S, Signorotti F, Perucca A, et al. Atypical arrhythmic complications in familial hypokalemic periodic paralysis. J Cardiovasc Med (Hagerstown ) 2009;10(1):68-71.
(e15) Kim MK, Lee SH, Park MS, et al. Mutation screening in Korean hypokalemic periodic paralysis patients: a novel SCN4A Arg672Cys mutation. Neuromuscul Disord 2004;14(11):727-731.
(e16) Bendahhou S, Cummins TR, Griggs RC, Fu YH, Ptacek LJ. Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis. Ann Neurol 2001;50(3):417-420.
(e17) Davies NP, Eunson LH, Samuel M, Hanna MG. Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK. Neurology 2001;57(7):1323-1325.
(e18) Venance SL, Jurkat-Rott K, Lehmann-Horn F, Tawil R. SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide. Neurology 2004;63(10):1977.
(e19) Vicart S, Sternberg D, Fournier E, et al. New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis. Neurology 2004;63(11):2120-2127.
(e20) Carle T, Lhuillier L, Luce S, et al. Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis. Biochem Biophys Res Commun 2006;348(2):653-661.