Hypokalemic Periodic Paralysis Type II: Mutations of the SCN4A Sodium Gene Presenting : Angela Galotti Jim Gettings Hala Mostafa The Rest :Matt Mancuso Bridget Matikainen Tee Pamon Visit us at:

Genetic Basis HOKPP2 is an autosomal dominant disease with varying degrees of penetrance Caused by mutations in the SCN4A gene Mapped to the 17q chromosome

Genetic Basis Single point mutations lead to amino acid substitutions Multiple transversions in codon 672 have been characterized Arginine is located in the voltage sensing domain Sternberg D, Maisonobe T, Jurkat-Rott K, Nicole S, Launay E, Chauveau D, et al. Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 2001; 124: 1091–9.

Functional Basis Crucial for proper sodium channel function Structural differences in the amino acids CCG->CGG CCG->CCA CCG->CAG

Symptoms of HOKPP2 Patients exhibit episodes of muscle weakness paralysis and low blood potassium Frequency and length of episodes vary Vital muscles that experience weaknesses can result in fatal attacks

Medical Diagnosis Medical background and history Sequencing and genetic analysis of genes Serum concentrations Babinski's reflex pecial%20Tests/babinkski.htm

Statistics of HOKPP2 Approximately 1 in 100,000 people are influenced Occurrences of the disorder depend on gender and age groups

Treatments Acetazolamide is used to prevent attacks

Treatments Potassium-sparing diuretics can be used to treat future attacks Dyrenium Spironolactone (shown right)‏ During an attack, potassium is given Medications result in less frequent and less serious attacks

Preventative Therapy Diets low in sodium and carbohydrates Avoid extreme temperature changes Mild (not strenuous) physical activity recommended

References 1. Sternberg D, Maisonobe T, Jurkat-Rott K, Nicole S, Launay E, Chauveau D, et al. Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 2001; 124: 1091–9. 2. Bulman DE, Scoggan KA, van Oene MD, Nicolle MW, Hahn AF, Tollar LL, et al. A novel sodium channel mutation in a family with hypokalemic periodic paralysis. Neurology 1999; 53: 1932–6. 3. Jurkat-Rott K, Mitrovic N, Hang C, Kouzmekine A, Iaizzo P, Herzog J, et al. Novel voltage sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc Natl Acad Sci USA 2000; 97: 9549– Mosenkis, Ari. Hypokalemic periodic paralysis. U.S. National Library of Medicine. 01 March article/ htm. 5. Sansone V, Meola G, Links T, Panzeri M, Rose M. Treatment for periodic paralysis. Cochrane Database Syst Rev Jan 23;(1)‏ 6. J.Finsterer(2008)Primary periodic paralyses Acta Neurologica Scandinavica 117 (3), 145–158 doi: /j x 7. Hypokalemic Periodic Paralysis: A Model for a Clinical and Research Approach to a Rare Disorder. Neurotherapeutics, Volume 4, Issue 2, Pages B. Fontaine, E. Fournier, D. Sternberg, S. Vicart, N. Tabti