Hypokalemic Periodic Paralysis Type II: Mutations of the SCN4A Sodium Gene

Presenting : Angela GalottiJim GettingsHala Mostafa

The Rest : Matt MancusoBridget MatikainenTee Pamon

Visit us at: www.sinc.sunysb.edu/Stu/mmancuso

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

http://oak.cats.ohiou.edu/~seegmill/spine_project/Special%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

References1. 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: 9549–54.

4. Mosenkis, Ari. Hypokalemic periodic paralysis. U.S. National Library of Medicine. 01 March 2006. http://www.nlm.nih.gov/medlineplus/ency/ article/000312.htm.

5. Sansone V, Meola G, Links T, Panzeri M, Rose M. Treatment for periodic paralysis. Cochrane Database Syst Rev. 2008 Jan 23;(1)

6. J.Finsterer(2008)Primary periodic paralyses Acta Neurologica Scandinavica 117 (3) , 145–158 doi:10.1111/j.1600-0404.2007.00963.x

7. Hypokalemic Periodic Paralysis: A Model for a Clinical and Research Approach to a Rare Disorder. Neurotherapeutics, Volume 4, Issue 2, Pages 225-232 B. Fontaine, E. Fournier, D. Sternberg, S. Vicart, N. Tabti