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HYPOKALEMIC PERIODIC PARALYSIS (HypoKPP)

CACNL1A3 (chromosomal locus 1q32), SCN4A (chromosomal locus 17q23.1-q25.3)

 
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PubMed Search for HypoKPP

The most prevalent form of periodic paralysis, HypoKPP, has been associated with mutations in the CACNL1A3 (calcium channel) gene, the SCN4A (sodium channel) gene, which is also a known site of mutations causing hyperkalemic periodic paralysis, and the KCNE3 (potassium channel) gene.

In her work with a large multi-generation family in the Netherlands, T. P. Links (1992) provided standard criteria for the preliminary diagnosis of Familial Hypokalemic Periodic Paralysis:

1. Observation of paralytic attacks by a physician or a typical history of paralytic attacks. Hypokalemia during attacks was often observed, but not prerequisite.

2. Characteristic histological findings in muscle biopsy.

3. Reduced muscle fiber conduction velocity (MFCV) in surface electromyographic EMG measurements plus presence of first degree relatives with proven diagnosis.

4. Progressive proximal muscle weakness plus first line relatives with HOPP (HypoKPP).

Among the conclusions reached by Links in her work with this family is that Familial HypoKPP is characterized by: 1) permanent muscle weakness at older age, often independent of paralytic attacks, and 2) attacks occur in about 60% of the patients, with a ratio of 3 (men) to 2 (women). Variability of muscle strength was present in 80% of the patients. Twenty percent of the patients, all without paralytic attacks, did not have complaints until permanent muscle weakness developed. Others, including Sternberg, et al. (Sternberg D, Maisonobe T, Jurkat-Rott K, Nicole S, Launay E, Chauveau D, Tabti N, Lehmann-Horn F, Hainque B, Fontaine B., Brain 2001 Jun;124 (Pt 6):1091-9), have also described HypoKPP as a muscle disorder characterized by episodic attacks of muscle weakness associated with a decrease in blood potassium levels.

Interestingly, Links reported that a diagnosis could only be made in 50% of the subjects by applying a number of supplementary diagnostic steps. Diagnosis, according to Links, could be made in the majority of the studied cases if (besides a positive family history) at least one of the following characteristics was present:

1) hypokalemia during paralytic attacks, without other detectable causes,

2) characteristic histological finding in muscle biopsy, without the presence of chronic hypokalemia, and

3) reduced muscle fiber conduction velocity and a low frequency content of the power spectra, without the interfering use of steroids or the presence of poly- or dermatomyositis.

The above provides an excellent example of how much variability can be found even within the limits of a single family. Others have confirmed Links’ general findings. Mendell, Griggs, and Ptacek (1998), describe HypoKPP as causing episodic weakness and flaccid paralysis, with the distinction of distal limb muscles being more effected than proximal, and “rarely, ocular, bulbar, or respiratory muscles are affected.” The latter is especially fortuitous as respiratory muscle weakness can prove to be fatal.

Ptacek and Griggs (1996) report the important characteristic that there “is no alteration of consciousness during these attacks and patients are often unable to walk and at times may be totally quadriplegic.” Ptacek and Griggs add that while the weakness that occurs during attacks of paralysis is usually confined to the limbs, it is not uncommon to find some facial and respiratory muscle weakness, and, “during attacks of severe weakness, patients may have subjective sensory symptoms but tests of sensation are invariably normal.” Mitrovic and Lerche (2000) add that “reflexes become hypoactive, and cardiac arrhythmias may occur during attacks owing to low serum potassium.”

HypoKPP Diagnostic Matrix

Also See:

Owners Manual for HypoKPP Michael M. Segal MD PhD, Karin Jurkat-Rott MD PhD, Jacob Levitt MD, Frank Lehmann-Horn MD PhD

Enhanced inactivation and pH sensitivity of Na(+) channel mutations causing hypokalemic periodic paralysis type II. Kuzmenkin A, Muncan V, Jurkat-Rott K, Hang C, Lerche H, Lehmann-Horn F, Mitrovic N.

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Section Last Modified:
12/29/2009 07:38 PT
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