Details

Autor(en) / Beteiligte

• Matthews, E
• Portaro, S
• Ke, Q
• Sud, R
• Haworth, A
• Davis, M B
• Griggs, R C
• Hanna, M G

Titel

Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype

Ist Teil von

• Neurology, 2011-11, Vol.77 (22), p.1960-1964

Ort / Verlag

United States

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• Acetazolamide has been the most commonly used treatment for hypokalemic periodic paralysis since 1968. However, its mechanism of efficacy is not fully understood, and it is not known whether therapy response relates to genotype. We undertook a clinical and genetic study to evaluate the response rate of patients treated with acetazolamide and to investigate possible correlations between response and genotype. We identified a total of 74 genotyped patients for this study. These included patients who were referred over a 15-year period to the only U.K. referral center or to a Chinese center and who underwent extensive clinical evaluation. For all genotyped patients, the response to acetazolamide therapy in terms of attack frequency and severity was documented. Direct DNA sequencing of CACNA1S and SCN4A was performed. Only 46% of the total patient cohort (34 of 74) reported benefit from acetazolamide. There was a greater chance of benefit in patients with mutations in CACNA1S (31 responded of 55 total) than in those with mutations in SCN4A (3 responded of 19 total). Patients with mutations that resulted in amino acids being substituted by glycine in either gene were the least likely to report benefit. This retrospective study indicates that only approximately 50% of genotyped patients with hypokalemic periodic paralysis respond to acetazolamide. We found evidence supporting a relationship between genotype and treatment response. Prospective randomized controlled trials are required to further evaluate this relationship. Development of alternative therapies is required.