HPP - underlying electrolyte pathophysiology

Q: Patients with hypokalemic Periodic Paralysis (HPP) usually have? - select one

A) Calcium channel disorders 

B) Potassium channel disorders

C) Sodium channel disorders 

Answer: A

Although, HPP is a potassium related pathophysiology as name suggests but the most common underlying gene mutations is a calcium channel disorder, involving the gene which codes for the alpha-1 subunit of the dihydropyridine-sensitive calcium channel in skeletal muscle.

Although not fully understood that how the calcium channel defect leads to episodic potassium movement into the cells leading to weakness. The proposed mechanism, along with few others, is that a gene disorder causes a decreased calcium current density and slower rate of activation. There could also be a pathology involving insulin sensitivity or hyperthyroidism.

Some patients may also have sodium channel disorders with a mutation in the skeletal muscle sodium channel, SCN4A, but not common. It affects males and females equally, in contrast to calcium channel disorders which affects mostly males.

Some patients may not have either of the above channels disorder but may have other potentially associated mutations.

#electrolytes

#musculoskeletal

References:

1. Ptácek LJ, Tawil R, Griggs RC, et al. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 1994; 77:863.

2. Matthews E, Labrum R, Sweeney MG, et al. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology 2009; 72:1544.

3. Ruff RL. Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K+ current. Neurology 1999; 53:1556.

4. Sternberg D, Maisonobe T, Jurkat-Rott K, et al. Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 2001; 124:1091.