title: Antenatal diagnosis of pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy.
abstract: Hypertrophic cardiomyopathy (HCM) affects most infants with Pompe disease (PD), and may serve as a marker for its antenatal diagnosis (ANDx) by fetal echocardiography (FE). Fetuses diagnosed with HCM between 2006 and 2009 were included in this study. HCM, defined as Z-score of mean left ventricular wall thickness (LVWT) and/or mass (LVM) above 2, was detected in 5/1,268 fetuses (0.39%) carried by 1,137 pregnant women referred for FE. Three fetuses (0.24%) had postnatal confirmation of PD. Their gestational age and fetal weight at diagnosis was (mean ± standard deviation) 31 ± 3.6 weeks and 1.9 ± 0.2 kg, respectively. Fetal Z-score of LVM and LVWT was 3.8 ± 0.9 and 3.1 ± 0.6, respectively. Postnatally, acid α-glucosidase (GAA) enzyme activity was nearly absent in all patients, 2 were homozygous for the mutation 1327-2A>G in the GAA gene, and 1 was homozygous for 340insT. Enzyme replacement therapy (ERT) was initiated 4.9 ± 7.8 days after birth (range 2 h-14 days), and continued every 2 weeks. Two infants are alive at 4 and 31 months, and one died of aspiration pneumonia at 19 months. Cardiac hypertrophy resolved after 10-12 weeks of ERT in all patients, and none required any respiratory support. One patient had normal neurodevelopmental assessment at 25 months, and one had severe global delay at 15 months before death. ANDx of PD by FE is feasible based on fetal HCM. It promotes early initiation of ERT which may improve outcome in some patients. However, larger studies and longer follow-ups are required.
authors.affiliation: Department of Pediatrics, Tawam Hospital, Al Ain, Abu Dhabi, PO Box 15258, United Arab Emirates. mhamdan@tawamhospital.ae
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Hamdan
authors.forename: Bushra A
authors.initials: BA
authors.lastname: El-Zoabi
authors.forename: Muzibunnisa A
authors.initials: MA
authors.lastname: Begam
authors.forename: Hisham M
authors.initials: HM
authors.lastname: Mirghani
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Almalik
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004452:Echocardiography; D056947:Enzyme Replacement Therapy; D005260:Female; D005318:Fetal Heart / Q000000981:diagnostic imaging*; D020567:Fetal Weight; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011247:Pregnancy; D013997:Time Factors; D016896:Treatment Outcome; D016216:Ultrasonography, Prenatal / Q000379:methods*; D000520:alpha-Glucosidases / Q000008:administration & dosage* / Q000235:genetics
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases
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