Antenatal diagnosis of pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy
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.
KeywordsCardiac Hypertrophy Enzyme Replacement Therapy United Arab Emirate Newborn Screening Glycogen Storage Disease
Source of funding
The authors confirm independence from any sponsor. The content of this article has not been influenced by any sponsor.
The first author (M.A. Hamdan) discloses limited consultation services and honorarium received from Genzyme Corp. (Cambridge, MA, USA). No financial support was received for preparing the manuscript.
Statement of Ethics
This manuscript was written in compliance with the regulations of the Human Research and Ethics Committee at our institution. Data regarding the patients’ clinical status were collected by chart review. Patients’ confidentiality was maintained during data collection and manuscript preparation.
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