Severe respiratory phenotype in a patient with HypoKPP

Submitted by deb on Fri, 03/01/2013 – 17:49

Severe respiratory phenotype caused by a de novo Arg528Gly mutation in the CACNA1S gene in a patient with hypokalemic periodic paralysis.

Authors Kil TH, et al.

Journal: Eur J Paediatr Neurol. 2010 May;14(3):278-81. doi: 10.1016/j.ejpn.2009.08.004. Epub 2009 Oct 12.

Affiliation: Department of Pediatrics, College of Medicine, Konyang University, 685 Gasoowon-dong, Su-goo, Daejun, Choongnam 302-718, South Korea.


Hypokalemic periodic paralysis (HOKPP) is a rare disorder characterized by episodic muscle weakness with hypokalemia. Mutations in the CACNA1S gene, which encodes the alpha 1-subunit of the skeletal muscle L-type voltage-dependent calcium channel, have been reported to be mainly responsible for HOKPP. The paralytic attacks generally spare the respiratory muscles and the heart.

Here, we report the case of a 16-year-old boy who presented with frequent respiratory insufficiency during the severe attacks. Mutational analysis revealed a heterozygous c.1582C>G substitution in the CACNA1S gene, leading to an Arg528Gly mutation in the protein sequence. The parents were clinically unaffected and did not show a mutation in the CACNA1S gene. A de novo Arg528Gly mutation has not previously been reported. The patient described here presents the unique clinical characteristics, including a severe respiratory phenotype and a reduced susceptibility to cold exposure. The patient did not respond to acetazolamide and showed a marked improvement of the paralytic symptoms on treatment with a combination of spironolactone, amiloride, and potassium supplements.

Copyright 2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

PMID 19822448 [PubMed – indexed for MEDLINE]