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Periodic Paralysis News Desk

Resources for the Periodic Paralysis Community since 1995

PHYSICIAN'S INFORMATION SHEET

Comparing the Periodic Paralyses

Introduction:

The major features found in all the periodic paralyses are:

  1. Almost without exception attacks begin before the age of 25.
  2. The level of potassium in the patient's blood fluctuates shortly before an attack, but potassium level is in the normal range between attacks.
  3. The attack may affect only one muscle or group of muscles, or it may affect the entire body.
  4. When weakness is on-going or affects only one group of muscles the change in the potassium level may be too small or temporary to measure.
  5. Speech, swallowing and breathing are not usually affected, but may be in severe attacks.
  6. Rest after exercise may provoke an attack, but mild attacks may sometimes be “walked off”, that is, if the patient can keep moving a mild attack may simply go away.
  7. Becoming chilled can provoke attacks.
  8. Deep tendon reflexes diminish and may disappear altogether during attacks.

In addition these further features are found in some forms of periodic paralysis:

  1. Myotonia or paramyotonia;
  2. Weakness between attacks; and
  3. Cardiac arrhythmias.

For the purpose of this discussion, the five types of periodic paralyses will be classified according to triggers and characteristics:

1) Hypokalemic Periodic Paralysis (HypoKPP)

Eleven mutations identified to date; five Ca++ on gene map locus 1q31-32: Arg528His, Arg1086Cys, Arg1086His, Arg1239His, Arg1239Gly; five Na+ at gene map locus 17q23.1-q25.3: Arg669His, Arg672His, Arg672Gly, Arg672Ser, Phe1158Ser, and one K+ on gene map locus 11q13-q14; Arg83His. Commercial testing is available for only three of these mutations.

Symptoms are precipitated by factors that cause K+ to move into the muscle cell, thus lowering the serum K+ level. Significant interattack weakness is common, especially in patients 35+. While many authorities agree that K+ levels need not fall below norm (3.5) to precipitate an attack, the name Hypokalemic Periodic Paralysis persists.

2) Thyrotoxic Periodic Paralysis(TPP)

No mutations identified, but a genetic predisposition is observed in Asians and Native Americans with Hyperthyroid Disease. Incidence in Caucasians with HD is 0.1%.

The thyrotoxicosis may present subclinically, especially for the first several attacks. Male predominance is 83% - 95%. TPP attacks are more common from May-October. Serum K+ usually falls to 2.0 and below during attacks. Except for the thyroid disease (Grave's Disease, thyroid adenoma) TPP symptoms are very much like genetic HypoKPP. Once patient is euthyroid TPP disappears.

3) Hyperkalemic Periodic Paralysis(HyperKPP)

Six mutations identified to date in Sodium Channel N4A chromosome 17q23-q25.3; Thr704Met; Ser906Thr; Ala1156Thr; Met1360Val; R1448C; Met1592Val. Commercial testing is available for one mutation. Patients with potassium-sensitive ("Hyper" KPP) respond to K+ rich foods or to K+ infusion with weakness. Their K+ level may not go above normal, (5.0) during an attack. In fact, toward the end of an attack the HyperKPP patient's K+ may drop below normal. This may result in diagnostic misadventure. The patient with HyperKPP usually experiences myotonia; muscle stiffness which can be worked off.

4) Paramyotonia Congenita (PMC) and Paramyotonia Syndromes"

20+ mutations identified in Sodium Channel N4A chromosome17q23-q25.3, including G1456E; L1433R, R1448C, Ser804Phe; Ile1160Val; Gly1306Ala; Gly1306Val; Gly 1306Glu; Val1589Met, Val1293Ile; Thr1313Met; Leu1433Arg; Arg1448Cys; Arg1448His; G1456E; Arg1448Pro; Val1458Phe; Phe1473Ser. Limited commercial testing is available.

There are several Paramyotonia syndromes. The most common is Paramyotonia Congenita (PMC), which may exist alone, or in combination with HyperKPP. The hallmark of these syndromes is paradoxical myotonia; myotonia which worsens with exercise. PMC can be potassium-sensitive or Hypokalemic in nature. The patient with the hypokalemic version of PMC may have it in combination with HyperKPP. Management for such patients must be fine - tuned for each individual. There are several paramyotonia syndromes. See accompanying chart on - site.

5) Andersen's Syndrome(AS)

Two mutations identified in the K+ channel NJ2 gene map locus 17q23; mutation Arg67Try. No commercial testing is available. In addition to attacks of weakness, Andersen's patients have a variety of cardiac rhythm disturbances, several of which may be life threatening. Some require defibrillators to manage their cardiac rhythm problems. It was thought until recently that all Andersen's patients had Long QTc intervals but new studies have shown that is not always the case. In a newly described family, females had cardiac abnormalities and males had periodic paralysis. None had long QTc. Andersen's patients may also have skeletal anomalies and dysmorphic features. Some Andersen's syndrome patients are consistently hypokalemic or hyperkalemic during attacks; others are hypokalemic during one attack and hyperkalemic the next.

For more detailed information see the Physician's Information Sheet on each of these forms.