Fetuses with signs of intrauterine heart disease should undergo enzymatic and genetic testing for Pompe disease, according to a recently published case report in the Italian Journal of Pediatrics.

Intrauterine-onset Pompe disease is very rare, with only a handful of cases reported. Notably, all cases had some form of myocardial involvement; however, manifestations vary between hypertrophic cardiomyopathy, dilated cardiomyopathy, and myocardial masses, according to Hongmin Xi, of Qingdao University in Shandong, China, and colleagues.

“Herein, we report a case of infantile Pompe disease with intrauterine onset manifesting clinical symptoms postnatally, markedly reduced [acid alpha-glucosidase (GAA)] enzymatic activity, and the presence of an uncommon homozygous mutation on genetic testing,” the authors wrote.

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The case involved a female neonate born at 40 weeks and 3 days of gestation with shortness of breath and cyanosis at 13 minutes; a previous ultrasound performed at 38 weeks of gestation revealed an enlarged heart with a thickened ventricular wall.

Physical examination at birth revealed poor responsiveness, pale skin, irregular breathing, positive Hoover’s sign in both lungs, and edema of the lower limbs. No heart murmurs were detected. Oxygen saturation was less than 90%.

An electrocardiogram showed PR interval prolongation, an abnormal Q wave, and ST-T changes. Echocardiography was consistent with the intrauterine findings, revealing thickening of the left ventricular wall and cardiac enlargement. Brain natriuretic peptide, creatinine kinase, and myoglobin levels were elevated at admission.

The newborn was admitted into the intensive care unit and put on assisted ventilation. Initial treatment included metoprolol intended to prevent future cardiac remodeling. Enzymatic testing revealed decreased GAA activity, and genetic testing revealed a missense mutation compatible with Pompe disease.

Due to financial issues and a poor prognosis, the parents refused enzyme replacement therapy. The patient died from cardiopulmonary failure 7 months after birth. 

“Infantile Pompe disease is a rare hereditary disease that can occur in utero, with initial signs being cardiac changes. Therefore, for fetuses with intrauterine cardiac disease, enzyme assays and genetic testing should be performed as soon as possible for early diagnosis and treatment,” the authors concluded.


Xi H, Li X, Ma L, Yin X, Yang P, Zhang L. Infantile Pompe disease with intrauterine onset: a case report and literature reviewItal J Pediatr. Published online November 21, 2022. doi:10.1186/s13052-022-01379-3