Clinical Characteristics Of Hypokalemic Periodic Paralysis And Genes Screening Of CACNA1S And SCN4A In Hypokalemic Periodic Paralysis

BackgroudHypokalemic periodic paralysis(HOKPP)is a kind of hereditary muscle disorder characterized by periodic episodes of flaccid myasthenia caused by ion channel dysfunction with hypokalemia,which includes primary hypokalemia periodic paralysis(PHOKPP)and secondary hypokalemic periodic paralysis(SHOKPP).PHOKPP includes familial hypokalemic periodic paralysis(FPP)and sporadic hypokalemic periodic paralysis(SPP).SPP mainly found in China.It has been confirmed that HOKPP is related to a variety of gene mutations.According to the statistics by European countries,calcium channel Voltage-dependent L type alpha(CACNA1S)and Sodium channel Voltage-dependent type ? alpha(SCN4A)are most common mutant genes.SPP is the most common type in China,but there are few studies on SPP genetics.ObjectiveExplore the clinical characteristics of patients with HOKPP and the characteristics of gene mutations in SPP.Methods1.The collection of clinical dataWe collected 114 patients diagnosed with HOKPP in January 2013-December 2016 in Nanhua Hospital,and according to the level of potassium concentration,divided into severe hypokalemia group(serum potassium <2.5 mmol/L),moderate hypokalemia group(serum potassium 2.5 mmol/L-3.0 mmol/L),mild hypokalemia group(serum potassium> 3.0 mmol/L).Record the general condition of the patient(age,gender,etiology,frequency,predisposing factors,concomitant symptoms),physical examination(muscle strength,muscle tension,tendon reflex),auxiliary examination(muscle enzymes,electrolytes,blood glucose,inflammatory indicators,ECG,EMG),treatment(potassium supplement,remission time,discharge time).2.Gene sequencingThe exon amplification sequencing of CACNA1 S and SCN4 A genes in 48 patients with SPP was performed by PCR and DNA sequencing,when the gene sequencing showed mutation,compared with the reference sequence in genebank and 100 cases of normal control group to determine whether the site mutation is a polymorphic site or a newly discovered mutation.If the mutation was confirmed as a newly discovered mutation,the corresponding loci of the parent will be tested to determine whether the mutation is a new mutation or a hereditary mutation.ResultsClinical characteristics:1)General condition: 114 HOKPP patients,the average age of onset is(38.1±1.4),the most common type is SPP,81.6% of patients are male.Compared with mild to moderate hypokalemia group,the incidence rate of male in severe hypokalemia group is higher,the incidence age in severe hypokalemia group is younger.2)Physical examination: all patients showed muscle weakness,symmetrical involvement of limbs,lower limbs is serious than upper limbs,muscle strength and serum potassium concentration is positively related.3)Auxiliary examination: the levels of CK and MB in HOKPP patients is higher than those in the normal level,severe hypokalemia group compares with mild to moderate hypokalemia group,CK,CK-MB,MB is higher.Blood glucose and inflammation index is higher than normal,in the moderate to severe hypokalemia group,the blood glucose is higher than that in mild hypokalemia group,in the severe hypokalemia group,WBC and N% is higher than that in mild to moderate hypokalemia group.Only 9.6% of patients have done electromyography,no myogenic damage was observed.44.3% of HOKPP has abnormal electrocardiogram and no correlation between serum potassium level and abnormal ECG.Gene mutation characteristics:In 48 SPP,4 SNP(c.597C>T/ p.I199 I,c.2748C>T/p.H939 H,c.3822C>T/p.I1274 I,c.5399T>C/p.L1800)were found in the CACNA1 S,3 SNP(C.366C>T/p.R122 R,c.1570A>G/p.S524 G,c.2289C>T/p.I763I)and a heterozygous missense mutation(c.1288A>G/ p.I430V)were found in the SCN4 A,the new missense mutation was highly conserved and was not observed in normal controls,and may be pathogenic.Conclusion1.In the patients of HOKPP,the moderate to severe hypokalemia is the most common type,most of patients are male,the muscle weakness in limb is symmetrical,the increase of CK is the main changs in creatases,and the contents of CK,CK-MB,and MB are negatively correlated with the concentration of serum potassium.2.The new mutation site c.1288A> G / p.I430 V in SCN4 A gene might be a pathogenic mutation site.