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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