title: Severe respiratory phenotype caused by a de novo Arg528Gly mutation in the CACNA1S gene in a patient with hypokalemic periodic paralysis.
abstract: 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.
authors.affiliation: Department of Pediatrics, College of Medicine, Konyang University, 685 Gasoowon-dong, Su-goo, Daejun, Choongnam 302-718, South Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kil
authors.forename: June-Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000584:Amiloride / Q000627:therapeutic use; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type; D003080:Cold Temperature / Q000009:adverse effects; D004252:DNA Mutational Analysis; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D011188:Potassium / Q000627:therapeutic use; D012131:Respiratory Insufficiency / Q000235:genetics* / Q000503:physiopathology; D013148:Spironolactone / Q000627:therapeutic use
chemical_list: C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D013148:Spironolactone; D000584:Amiloride; D001120:Arginine; D011188:Potassium; D005998:Glycine