[Hyperkalemic periodic paralysis: a Spanish family with the p.Thr704Met mutation in the SCN4A gene].
BACKGROUND
Hyperkalemic periodic paralysis (HYPP) is an autosomal dominant disease characterized by recurrent episodes of muscular weakness with increased blood potassium levels. Here we present the clinical, analytical, neurophysiological and genetic findings of family with eight affected individuals, five of which were available for study.


METHODS
The five patients were subjected to complete anamnesis, neurological examination, routine blood analysis and genetic study. Two of the patients were also examined both at the clinical and neurophysiological levels. In one case, the potassium levels were determined during a crisis.


RESULTS
Almost all patients presented 2 to 3 episodes of muscle weakness of the limbs per day of 30-45 min, and showed calf hypertrophy. During the observed episodes, the paralysis was massive in the lower limbs and the patients showed generalized osteotendinous areflexia. The potassium levels of the probandus measured during one of the episodes were elevated. The genetic analysis showed that all the affected individuals carried the p.Thr704Met mutation in the a subunit of the skeletal muscle sodium channel, encoded by the SCN4A gene.


CONCLUSIONS
Our findings correlate well with those reported previously in HYPP, although the frequency of the episodes is exceptionally high in our family. HYPP is a channelopathy caused by mutations in the SCN4A gene, although molecular alterations have only been identified in 70 % of the patients. The affected members of the studied family bear a frequent mutation, p.Thr704Met, associated with a severe presentation of the disease.
Narberhaus
B
B
Servicio de Neurologia, Hospital Sant Joan de Déu (Fundación Althaia), Manresa, Barcelona. 19345bnd@comb.es
Cormand
B
B
Cuenca-León
E
E
Ribasés
M
M
Monells
J
J
D000818:Animals; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062553:NAV1.4 Voltage-Gated Sodium Channel; D020513:Paralysis, Hyperkalemic Periodic / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D015222:Sodium Channels / Q000235:genetics*; D013030:Spain
D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels