Primary periodic paralysis – PP

Rare autosomal dominant (even sporadic) neuromuscular disorders related to mutations of sodium, potassium and calcium channels of muscle cells.

Their common feature is crisis of muscle paralysis, often triggered by behavior or food related to the concentration of sodium in blood.

They include hypokalemic paralysis (HypoPP), hyperkalemic paralysis (HyperPP) and Andersen – Tawil syndrome.

Incidence of HypoPP is estimated 1:100,000, for HyperPP 1:200,000 and for Andersen – Tawil 1: 1,000,000.

HypoPP is related to mutations in CACNA1S gene (calcium channel gene) (60%) and in SCN4A gene (sodium channel gene)(20%).

HyperPP is related to SCN4A gene and Andersen – Tawil syndrome is related to KCNJ2, which for an important protein for potassium flow in the channel of skeletal and heart muscles.   In this syndrome multiple tissues are affected and are related periodic paralysis symptoms, heart arrhythmias and particular face and skeletal abnormalities.

Clinical Features

HypoPP is characterized by local or generalized paralytic episodes in skeletal muscles, that might occur from hours to days related to hypokalemia. Myopathy evolves and leads to muscle weakness close to lower limbs. The first crisis usually occurs between the ages of 5 to 35 years old, but occur more often after 15 years old till 35, and gradually become less.

HyperPP is characterized by limb muscle weakness and sodium increase in blood. Crisis of muscle weakness start usually from the first decade of life (50%), without excluding the fact that they might occur from earlier than the age of 10 (25%), which last 2 hours. Most of the patients (80%) develop permanent muscular weakness, and 1/3 chronic and progressive myopathy.

Andersen – Tawil syndrome is characterized by the triad of periodic paralysis episodes, heart abnormalities and skeletal characteristics in 58-78% of the patients with mutations in KCNJ2 gene. Symptoms occur in the first or the second decade in life either with heart problems or with muscle weakness, which gradually becomes permanent and potentially life threatening.

Diagnosis

It could be conducted through molecular test and clinical exam, since all paralytic cases have certain clinical features. Use of electrodiagnostic methods and via particular physical exercises could also be diagnostic tools.

 

General therapeutic approaches  

They mainly include patient education with every possible change in their way of living, so they could avoid triggering a paralytic crisis. Dietary advices and some drug interventions, eventhough limited, could greatly contribute. Especially, in the case of Andersen – Tawil, a specialist cardiologist is needed for heart arrhythmias and definitely for the prevention of malignant hyperthermia, in case of anesthetic drugs.

References

  1. Statland J.M. et al, Review of the diagnosis and treatment of periodic paralysis, Muscle & Nerve, 2018, pp. 522-530.
  2. Tristani-Firouzi M. et al, Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome), The Journal of Clinical Investigation, 2002, 110, 3, pp. 381-388.