Mei-Hwan Wu

Early Detection of Pompe Disease by Newborn Screening Is Feasible: Results From the Taiwan Screening Program

OBJECTIVE. Pompe disease is an autosomal recessive lysosomal storage disorder that is caused by deficient acid α-glucosidase activity and results in progressive, debilitating, and often life-threatening symptoms involving the musculoskeletal, respiratory, and cardiac systems. Recently, enzyme replacement therapy with alglucosidase α has become possible, but the best outcomes in motor function have been achieved when treatment was initiated early. The aim of this study was to test the feasibility of screening newborns in Taiwan for Pompe disease by using a fluorometric enzymatic assay to determine acid α-glucosidase activity in dried blood spots. METHODS. We conducted a large-scale newborn screening pilot program between October 2005 and March 2007. The screening involved measuring acid α-glucosidase activity in dried blood spots of ∼45% of newborns in Taiwan. The unscreened population was monitored as a control. RESULTS. Of the 132 538 newborns screened, 1093 (0.82%) repeat dried blood-spot samples were requested and retested, and 121 (0.091%) newborns were recalled for additional evaluation. Pompe disease was confirmed in 4 newborns. This number was similar to the number of infants who received a diagnosis of Pompe disease in the control group (n = 3); however, newborn screening resulted in an earlier diagnosis of Pompe disease: patients were <1 month old compared with 3 to 6 months old in the control group. CONCLUSIONS. To our knowledge, this is the first large-scale study to show that newborn screening for Pompe disease is feasible. Newborn screening allows for earlier diagnosis of Pompe disease and, thus, for assessment of the value of an earlier start of treatment.

The 1998 Enterovirus 71 Outbreak in Taiwan: Pathogenesis and Management

The most recently discovered enterovirus, enterovirus 71 (EV71), is neurotropic and may cause severe disease and sudden death in children. In 1998, a large outbreak of enterovirus infection occurred in Taiwan that resulted in 405 severe cases in children and 78 deaths. Of the 78 children who died, 71 (91%) were <5 years old. EV71 was the primary agent in fatal cases of infection. Most of these patients died within 1-2 days of admission to the hospital. We hypothesize that EV71 directly attacks the central nervous system and causes neurogenic pulmonary edema and cardiac decompensation through the mechanism of sympathetic hyperactivity and inflammatory responses. Early recognition of risk factors and intensive care are crucial to successful treatment of this fulminant infection. After poliovirus is eradicated, EV71 will become the most important enterovirus that affects children, and development of a vaccine may be the only effective measure against it.

Epidemiologic Features of Kawasaki Disease in Taiwan, 2003–2006

OBJECTIVE. Kawasaki disease is the leading cause of acquired heart disease in children worldwide. This study characterizes the epidemiology of Kawasaki disease in Taiwan between 2003 and 2006. METHODS. Using Taiwans 2003–2006 national health insurance claims, we investigated the epidemiologic features of Kawasaki disease (ICD-9-CM code 446.1) and coronary artery aneurysm formation (International Classification of Diseases, Ninth Revision, Clinical Modification code 414.11) and compared the incidences of these diseases with those occurring between 1996 and 2002 in Taiwan and those reported by other countries. RESULTS. During our 4-year study period, 3877 children and adolescents <20 years of age were hospitalized for Kawasaki disease. Ninety percent of these children were <5 years of age, and the male/female ratio was 1.62:1. The annual incidence of Kawasaki disease was 153 in 100000 children <1 year of age, 111 in children 1 year of age, 58 in children 2 years of age, 30 in children 3 years of age, 19 in children 4 years of age, and 5.2 in children 5 to 9 years of age. The overall incidence was 69 cases per 100000 for children <5 years of age. Kawasaki disease recurred in 1.5% of all cases. Kawasaki disease occurred most frequently in the summer and least frequently in the winter. Coronary artery aneurysm occurred in 7.2% (279 of 3877) of all Kawasaki disease cases. CONCLUSIONS. The overall incidence of Kawasaki disease was 69 in 100000 children <5 years of age between 2003 and 2006 in Taiwan, comparable with the incidence of 66 in 100000 children between 1996 and 2002. Taiwan has the third highest incidence of Kawasaki disease in the world, after Japan and Korea. In Taiwan, it occurs more frequently during the summer.

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association.

Background: Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. Methods and Results: To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and long-term outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. Conclusions: These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.

Pompe Disease in Infants: Improving the Prognosis by Newborn Screening and Early Treatment

OBJECTIVE: Pompe disease causes progressive, debilitating, and often life-threatening musculoskeletal, respiratory, and cardiac symptoms. Favorable outcomes with early intravenous enzyme-replacement therapy and alglucosidase alfa have been reported, but early clinical diagnosis before the development of severe symptoms has rarely been possible in infants. METHODS: We recently conducted a newborn screening pilot program in Taiwan to improve the early detection of Pompe disease. Six of 206088 newborns screened tested positive and were treated for Pompe disease. Five had the rapidly progressive form of Pompe disease, characterized by cardiac and motor involvement, and were treated soon after diagnosis. The sixth patient was started on treatment at 14 months of age because of progressive muscle weakness. Outcomes were compared with treated patients whose disease was diagnosed clinically and with untreated historical control subjects. RESULTS: At the time of this report, patients had been treated for 14 to 32 months. The 5 infants who had early cardiac involvement demonstrated normalization of cardiac size and muscle pathology with normal physical growth and age-appropriate gains in motor development. The infant without cardiac involvement also achieved normal motor development with treatment. Survival in patients who had newborn screening was significantly improved compared with those in the untreated reference cohort (P = .001). Survival in the treated clinical comparators was reduced but not statistically different from that in the newborn screening group (P = .48). CONCLUSIONS: Results from this study indicate that early treatment can benefit infants with Pompe disease and highlight the advantages of early diagnosis, which can be achieved by newborn screening.

Prevalence of Congenital Heart Disease at Live Birth in Taiwan

OBJECTIVES To investigate the prevalence at live birth of congenital heart disease (CHD) in Taiwan. STUDY DESIGN Patients with CHD born from 2000 to 2006 were identified from National Health Insurance databases. RESULTS CHD prevalence was 13.08 per 1000 live births: 12.05 (simple, 10.53; severe, 1.51) in male infants and 14.21 (simple, 12.90; severe, 1.32) in female infants. Ventricular septal defect (VSD; 4.0) was the most common defect, followed by secundum atrial septal defect (ASDII; 3.2), patent ductus arteriosus (PDA; 2.0), pulmonary stenosis (PS; 1.2), tetralogy of Fallot (TOF; 0.63), coarctation of aorta (CoA; 0.25), transposition of great arteries (TGA; 0.21), endocardial cushion defect (ECD; 0.20), double outlet of right ventricle (DORV; 0.15), total anomalous pulmonary venous return (TAPVR; 0.11), aortic stenosis (0.09), hypoplastic left heart syndrome (HLHS; 0.062), Ebstein anomaly (0.047), and tricuspid atresia (0.046). Female predominance was observed in VSD, ASDII, PDA, and ECD; and male predominance was observed in TGA and TOF. Ratios of western prevalence to our Asian prevalence were high for HLHS (3.68-4.5), CoA (1.13-1.96), TGA (1.09-1.83), and tricuspid atresia (1.09-2.57), but low for PS (0.15-0.99), TOF (0.41-0.92), and possibly ASDII. CONCLUSIONS In this Asian population, the prevalence of CHD was at the high end of the reported range, with more PS and TOF, but fewer left-sided obstructions, TGA, and tricuspid atresia.

Losartan Added to β-Blockade Therapy for Aortic Root Dilation in Marfan Syndrome: A Randomized, Open-Label Pilot Study

OBJECTIVE To assess the tolerability and efficacy of the investigational use of the angiotensin II receptor blocker losartan added to β-blockade (BB) to prevent progressive aortic root dilation in patients with Marfan syndrome (MFS). PATIENTS AND METHODS Between May 1, 2007, and September 31, 2011, 28 patients with MFS (11 males [39%]; mean ± SD age, 13.1±6.3 years) with recognized aortic root dilation (z score >2.0) and receiving BB (atenolol or propranolol) treatment were enrolled. They were randomized to receive BB (BB: 13 patients) or β-blockade and losartan (BB-L: 15 patients) for 35 months. RESULTS In the BB-L group, aortic root dilation was reduced with treatment, and the annual dilation rate of the aortic root was significantly lower than that of the BB group (0.10 mm/yr vs 0.89 mm/yr; P=.02). The absolute aortic diameters at the sinus of Valsalva, annulus, and sinotubular junction showed similar trends, with a reduced rate of dilation in the BB-L group (P=.02, P=.03, and P=.03, respectively). Five patients (33%) treated with BB-L were noted to have a reduced aortic root diameter. However, the differences between the groups regarding changes in aortic stiffness and cross-sectional compliance were not statistically significant. CONCLUSION This randomized, open-label, active controlled trial mostly based on a pediatric population demonstrated for the first time that losartan add-on BB therapy is safe and provides more effective protection to slow the progression of aortic root dilation than does BB treatment alone in patients with MFS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00651235.

Supraventricular tachycardia in patients with right atrial isomerism

OBJECTIVES To clarify the prevalence and mechanism of supraventricular tachycardia in patients with right atrial isomerism. BACKGROUND Paired SA and dual atrioventricular (AV) nodes have been described in patients with right atrial isomerism. However, the clinical significance remains unclear. METHODS From 1987 to 1996, a total of 101 patients (61 male, 40 female) and four fetuses were identified with right atrial isomerism. The diagnosis of supraventricular tachycardia exclude the tachycardia with prolonged QRS duration or AV dissociation, and primary atrial tachycardia. RESULTS The median follow-up duration was 38 months (range 0.2-270 months). Supraventricular tachycardia was documented in 25 patients (24.8%) and one fetus (25%) (onset age ranged from prenatal to 14 years old; median 4 years old). Actuarial Kaplan-Meier analysis revealed that the probability of being free from tachycardia was 67% and 50% at 6 and 10 years of age, respectively. These tachycardias could be converted by vagal maneuvers in one, verapamil in seven, propranolol in four, digoxin in two, procainamide in one, and rapid pacing in five. Spontaneous conversion was noted in six (including the fetus). Seven cases had received electrophysiological studies. Reciprocating AV tachycardia could be induced in five and echo beats in one. The tachycardia in three patients was documented as incorporating a posterior AV node (antegrade) and an anterior or a lateral AV node (retrograde). Two of them received radiofrequency ablation. Successful ablation in both was obtained by delivering energy during tachycardia, aimed at the earliest retrograde atrial activity and accompanied by junctional ectopic rhythm. The patient with echo beats developed tachycardia soon after operation. CONCLUSIONS Supraventricular tachycardia is common in patients with right atrial isomerism and can occur during the prenatal stage. Drugs to slow conduction through the AV node may help to terminate the tachycardia. Radiofrequency ablation is a safe and effective treatment alternative to eliminate tachycardia.

Transcatheter closure of moderate to large patent ductus arteriosus with the Amplatzer duct occluder

To investigate the acute and follow‐up results of transcatheter closure of moderate to large patent ductus arteriosus (PDA) with the Amplatzer duct occluder.

Rheumatic fever recurrences: controlled study of 3-week versus 4-week benzathine penicillin prevention programs

To compare the merits of 3-week versus 4-week injections of benzathine penicillin G in preventing recurrence of rheumatic fever, 179 patients aged 4 to 19 years were assigned to one of the two programs. Age, weight, cardiac status, and streptococcal infections among the patients and their family members studied in each program were comparable. Eight-two patients and their family members were monitored for streptococcal infections. Compliance in the two programs was comparable. Of the 63 patients who stayed in the 4-week program, RF recurred in six, as a result of prophylaxis failure in five and associated with partial compliance in one. Of the 90 patients in the 3-week program, RF recurred in one, associated with partial compliance; no failures occurred (P = 0.01). We recommended that for RF chemoprophylaxis in individuals at great risk, regardless of age, benzathine penicillin injections should be administered every 3 rather than every 4 weeks.