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This is a rare condition characterised by episodes of generalised flaccid weakness or paralysis associated with transient reductions in serum potassium levels.
The condition is due to a mutation on chromosome 17. It is inherited in a typical autosomal dominant pattern with a penetrance that is about 90% in males, but around 50% in females. Around a third of cases give no family history and so may be spontaneous mutations.
Hypokalaemic periodic paralysis (HOKPP) has a prevalence of 1 case per 100,000 population.
- It tends to present in the second decade of life but may be in the first decade with more severe disease and the third decade in milder cases. The majority present before 16 years of age.
- The frequency declines by the age of 30 years and it rarely occurs after the age of 50 years.
At the beginning, attacks may only be occasional but tend to become more frequent until occurring almost daily:
- Weakness may range from severe and generalised to limited to a particular muscle group, or only transient weakness.
- Not all muscle groups are affected:
- The heart, diaphragm and other muscles of ventilation are spared.
- There tends to be sparing also of the muscles supplied by the cranial nerves.
- Severe attacks usually begin in the morning, when there has often been strenuous exercise or a high-carbohydrate meal on the previous day.
- Patients awake with marked symmetrical weakness, often with truncal involvement:
- Mild attacks are frequent and involve only a limited group of muscles, and may be unilateral, partial, or affecting just one muscle.
- This may predominantly affect the legs.
- Sometimes extensor muscles are affected more than flexors.
- The duration of weakness can vary, seldom exceeding 72 hours, but has been known to persist for one week..
- Urinary output is reduced during an attack.
- Between attacks, myotonia may occur but is unusual. Myotonic lid lag may be observed between attacks.
- Later in the course of the disease, permanent muscle weakness may be seen and it may become severe. Hypertrophy of the calves has been observed. Proximal muscle wasting, rather than hypertrophy, may be seen in patients with permanent weakness.
Aggravating and relieving factors
The condition can be precipitated by insulin or glucose infusion:
- Glucose will cause the endogenous release of insulin that causes both glucose and potassium to move into cells.
- This would also explain the precipitation of an attack by high-carbohydrate meals.
Attacks can be aborted by administration of potassium or by exercise.
- Hyperkalaemic periodic paralysis (HYPP) is very similar clinically. It is also an autosomal dominant condition causing paralytic attacks (but with high rather than low potassium during an attack) and with myotonia more commonly seen.
- Another variant that is genetically determined, apparently from mutation on the 1 chromosome, is thyrotoxic periodic paralysis, in which hypokalaemic paralysis is associated with thyrotoxicosis. 85% of cases are in males of Asian descent.
- Secondary hypokalaemia will cause weakness and there are a number of causes:
Between attacks, parameters may be normal.
- During an attack the plasma potassium level is decreased, although it may not fall below the normal or reference range.
- Urine output is low with elevated urine levels of sodium, potassium, and chloride.
- There is a fall in serum phosphate levels, whilst creatine phosphokinase (CPK) is elevated during an attack.
- It may be possible to distinguish the primary condition from secondary periodic paralysis from potassium loss by the ratio of urinary creatinine to potassium (CRP). In molar terms, if the CRP exceeds 2.5, there is secondary potassium loss.
- The ECG may show sinus bradycardia with evidence of hypokalaemia, including flattening of T waves, U waves in leads II, V2, V3, and V4, and ST segment depression.
Provocative testing, eg exercise test, or insulin or glucose infusion, can be employed but, for safety, is best within secondary care:
- A doctor should be present during testing.
- It should be performed in a setting where intensive care, such as ventilation, may be provided if required, with facilities for rapid electrolyte and glucose testing and correction.
- Do not test patients with serum potassium disturbances, diabetes mellitus, or renal or cardiac dysfunction.
- There must be close monitoring of the ECG.
Oral or intravenous (IV) potassium, depending on whether patients are able to swallow:
- Oral potassium salts, at a dose of 0.25 mmol/kg bodyweight, should be given every 30 minutes until the weakness improves.
- Continuous ECG monitoring and serial potassium measurements are essential.
- Acetazolamide may be used at a dose of 125-1,500 mg/day in divided doses.
- A recent Cochrane review found dichlorphenamide was significantly better than placebo for prophylaxis in hypokalaemic periodic paralysis (HOKPP) or in hyperkalaemic periodic paralysis (HYPP).
- Potassium-sparing diuretics like triamterene (25-100 mg/day) and spironolactone (25-100 mg/day) are second-line drugs to be used in patients in whom the weakness worsens or in those who do not respond to carbonic anhydrase inhibitors.
- As these diuretics are potassium-sparing, potassium supplements may not be necessary.
- Topiramate is an antiepileptic drug with carbonic anhydrase inhibitory properties. A case report documented patients experiencing a decrease in the severity of their attacks upon initiation of treatment.
There is no evidence base for the management of HOKPP in pregnancy.
Attacks can be minimised by a very low-sodium diet and avoidance of meals that are high in carbohydrate.
Further reading and references
Garth D; Hypokalemia in Emergency Medicine, Medscape, Apr 2012
Sternberg D, Tabti N, Hainque B, et al; Hypokalemic Periodic Paralysis. GeneReviews®. Seattle (WA): University of Washington, Seattle 1993-2016.
Sripathi N; Periodic Paralyses, eMedicine, Nov 2010
Hyperkalaemic Periodic Paralysis; HYPP, Online Mendelian Inheritance in Man (OMIM)
Lin SH, Lin YF, Chen DT, et al; Laboratory tests to determine the cause of hypokalemia and paralysis. Arch Intern Med. 2004 Jul 26
McManis PG, Lambert EH, Daube JR; The exercise test in periodic paralysis. Muscle Nerve. 1986 Oct
Sansone V, Meola G, Links TP, et al; Treatment for periodic paralysis. Cochrane Database Syst Rev. 2008 Jan 23(1):CD005045.
Fiore DM, Strober JB; Treatment of hypokalemic periodic paralysis with topiramate. Muscle Nerve. 2011 Jan43(1):127-9.
Levitt JO; Practical aspects in the management of hypokalemic periodic paralysis. J Transl Med. 2008 Apr 216:18.
Ahlawat SK, Sachdev A; Hypokalaemic paralysis. Postgrad Med J. 1999 Apr75(882):193-7.
Hello is there anyone out there in the UK with adult Hypophosphatasia. If so I would be grateful to hear from you as I am searching for support and answers. Many thanks.Elderberry.Elderberry
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