A report on disease management and research as of July 2009
This “In Focus” report is part of a series of MDA comprehensive reports about the latest in neuromuscular disease research and management.
This report focuses on the periodic paralyses, a group of disorders that result from malfunctions in so-called ion channels, microscopic tunnels that make possible high-speed movement of electrically charged particles across barriers inside cells and between cells and their surroundings.
When ion channels fail to open or close according to an exquisitely fine-tuned program, episodes of paralysis of the skeletal muscles and even temporary irregularities in the heartbeat can occur.
Throughout history, and unfortunately down to the present day, people who experience episodes of paralysis or weakness, interspersed with periods of normal functioning, have been met with suspicion by their peers and even their doctors. Individuals have been accused of faking their attacks to gain attention or shirk their responsibilities, and parents have been suspected of child abuse when their children displayed these mysterious symptoms.
Today, molecular biology has pinpointed the precise mechanisms that underlie the periodic paralyses, and drug trials to treat them are under way. There is much work to be done, but awareness of the diagnosis can provide significant reassurance and help in managing these conditions.
Experience a typical periodic paralysis episode in the poem A Day in the Life of a Periodic Paralysis Patient.
MDA’s three-year commitment for all periodic paralysis research as of March 2009 is $1,938,367. The Association’s allocation for research on hyperkalemic and hypokalemic periodic paralysis research since 1950 is $8,125,341. MDA’s allocation for the recently identified Andersen-Tawil syndrome is $515,430 since 2001. MDA is currently funding 11 grants in the periodic paralyses.
The periodic paralyses are generally divided into hyperkalemic periodic paralysis, hypokalemic periodic paralysis and Andersen-Tawil syndrome. The first two are caused by genetic defects in high-speed tunnels in skeletal muscle fibers known as ion channels. The last is due to such defects in both skeletal and cardiac muscle.
All forms of periodic paralysis affect both sexes equally and are inherited in a dominant manner, meaning only one genetic flaw (mutation) from one parent can cause the disease.
Hyperkalemic periodic paralysis
Hyperkalemic PP usually begins early in childhood, with episodes of muscle weakness or paralysis lasting from 15 minutes to hours or even days. With time, some people develop permanent mild or moderate weakness that persists between bouts of severe weakness. Some patients also experience episodes of myotonia, the inability to relax muscles completely.
The underlying cause is any of several genetic mutations in a gene on chromosome 17 that carries instructions for a sodium channel protein. The sodium channels in skeletal muscle can’t close properly, permitting an excess of sodium ions to enter the muscle fibers.
Hypokalemic periodic paralysis
Hypokalemic PP can begin anywhere from early childhood to the 30s, with periodic attacks of severe weakness lasting hours to days. The frequency of attacks generally lessens in the 40s or 50s. Permanent weakness may persist between attacks, usually beginning in middle age and progressing slowly over years.
The most common underlying cause is any of several genetic mutations in a gene on chromosome 1 that carries instructions for a calcium channel protein in skeletal muscle fibers. When this channel fails to transmit a signal to a calcium storage area inside the cell, the muscle fiber can’t contract. A minority of people have sodium channel mutations, but not the same ones that cause hyperkalemic periodic paralysis.
This syndrome usually begins in childhood or adolescence and is characterized by episodes of weakness of the skeletal muscles and irregular heartbeat in the cardiac muscle. Occasionally people may develop permanent weakness between episodes. Heartbeat irregularities can be serious enough to warrant treatment with medication or electronic devices. Widely spaced eyes, low-set ears and a small chin also are characteristic of this disorder.
The underlying cause of Andersen-Tawil syndrome is any of a number of genetic mutations in a chromosome 17 gene for a potassium ion channel present in both skeletal and cardiac muscle tissue. When these channels fail to open, the exit of potassium from muscle cells after they contract is impaired, and the cells can’t “reset” to receive further contraction signals.anesthetics and depolarizing muscle relaxants