Primary Carnitine Deficiency-induced Cardiomyopathy:Clinical And Genetic Features And Therapeutic Outcome

Objective: To explore 8 Primary carnitine deficiency(PCD)-induced cardiomyopathy patients' clinical features,gene mutations and evaluate the efficacy of carnitine in the treatment of PCD.Methods: We found 8 patients including 3 males and 5 females diagnosed as primary carnitine deficiency-induced cardiomyopathy during the period March 2010 to May 2013 in Shanghai Children's Medical Center: affiliated to Shanghai Jiaotong University of Medicine,summarized and analyzed the patients' clinical features,the results of gene test and echocardiography,EKG,plasma free carnitine level and the time when the plasma free carnitine level concentration to normal,and the follow-up of the L-carnitine therapy.Results 1.8 patients were diagnosed of PCD-induced cardiomyopathy in our hospital including 3 males and 5 females,average ages was 8~77 months when being diagnosed,all of them were undergoing compromised cardiac functions.Moreover,5 patients had respiratory tract infection or pneumonia,4 of them had myasthenia an d one with stomachache.2.The average of the first screen plasma free carnitine concentration was(1.38±0.61)?mol/L and other kinds of acyl carnitine decreased,before receiveing the treatment.Some of the patients had a little increase of Creative kinase(CK),Creative kinase MB(CKMB),Cardiac troponin I(cTnI),N-terminal pro-B-type natriuretic peptide(NT-proBNP);and 1 patient whose liver function was impaired his Alanine aminotransferase(ALT)increased,5 patient had anemia,the level of Hemoglobin(Hb)was lower.3.Before the L-carnitine therapy,all of the patients have the left ventricular enlargement,the left ventricular end-diastolic diameter(LVDd)was(5.29±0.70)cm,the Z scores was(5.6±1.7);the Left Ventricular Posterior Wall Diameter(LVPWd)was(0.60±0.26)cm,the Z scores was(1.6 ± 1.7),2 patients with left ventricular hypertrophy.And with the reduction of left ventricular systolic function,the left ventricular ejection fraction was(38.13±11.13)%.The patients` QT interval were abnormal short,the Corrected QT interval were(357.50±12.35)ms,5 patients with high T waves.4.After the treatment in the early,the symptoms of cardiac insufficiency and myasthenia were reduced.The free carnitine level came to (23.51±14.93)?mol/L,and LVDd decreased to(4.32±0.59)cm,and the Z scores was(3.5±1.9),the LVEF was(55.7±5.1)% and the QTc prolonged to(406.88±24.57)ms.5.Half a year after the treatment,the symptoms of cardiac insufficiency and myasthenia were reduced furtherly.And the free carnitine level came to the normal,it`s(18.97±6.46)?mol/L,LVDd decreased to(3.63±0.6)cm and the Z scores was(1.4±1.1),4 patients still had cardiac dilatation.LVEF increased to(67.8±9.5)%,the Z scores of the LVPWd was(2.3±1.5)and QTc was(397.50±23.72)ms.6.One year after the treatment,the symptoms of cardiac insufficiency disappeared and the myodynamia was normal.And the free carnitine level was(12.69±2.80)?mol/L,LVDd decreased to(3.69±0.35)cm and the Z scores was(1.2±0.7),LVEF increased to(68.9±12.9)%,the Z scores of the LVPWd was(1.5±1.1)and QTc was(392.29±19.58) ms.7.Two years after the treatment,all of the patients had not any symptoms of the cardiac insufficiency and myasthenia.The free carnitine level was(19.98±7.42)?mol/L,LVDd was(3.75±0.40)cm and its Z scores was(0.9±0.7),LVEF was(69.7±6.6)% and QTc was(395.00±17.77)ms.8.All of the patients were finished the gene test,and 9 different mutation sites,including c.338G>A(p.C113Y)and c.51C>G(p.F17L) in exon 1,c.433 ins A and c.497+1G>A in exon 2,c.517 del C in exon 3,c.700G>C(p.G234R)and c.760C>T(p.R254X)in exon 4, c.865C>T(p.R289X)in exon 5,c.1327T>A(p.F443I)in exon 8.And 6 patients' mutations were confirmed from their parent.Among them, c.760C>T(p.R254X)has the highest mutation.Conclusions 1.Primary carnitine deficiency was associated with cardiomyopathy as an etiologic factor,and more attention should be paid to the PCD screening in the children with cardiomyopathy.2.The free carnitine level was lower than normal,with dilated cardiomyopathy and/or hypertrophic cardiomyopathy,and myasthenia, liver dysfunction,anemia in the PCD induced cardiomyopathy.And the GC/MS is an important screening way of PCD 3.After the treatment in early,the free carnitine level and QT interval came to normal,LVDd was reduced and LVEF increased significantly,the cardiac function and myasthenia were improved.4.During the median-and long follow up,all of the clinical symptoms disappeared,and the cardiac function and structure was normal,it had obviously median-and long-effect with keeping the oral of L-carnitine.5.All of the patients had been found the mutations in the SLC22A5 gene,mainly in exon 1?2?4,and c.760C>T(p.R254X)in exon 4 was the most common mutation.And the mutation c.1327T>A(p.F443I)was de nove,the genetic test can be used as a way of PCD diagnosis.