A case report of a baby boy diagnosed with abnormal fluid accumulation due to infantile-onset Pompe disease highlights the importance of considering this type of Pompe as the root cause, especially in states that don’t screen newborns for the disease, researchers said.
The case was briefly described in the correspondence article “Infantile onset Pompe disease presenting with non-immune hydrops fetalis” published in Molecular Genetics and Metabolism Reports.
Abnormal fluid build-up in at least two fetal compartments is a well-recognized fetal and neonatal condition known as hydrops fetalis. It is considered the end-stage of several disorders. Non-immune hydrops fetalis (NIHF) is a form of this condition.
Around 15% of NIHF cases are estimated to be caused by rare genetic disorders that interfere with metabolism, meaning the body cannot properly turn food into energy.
Lysosomal storage disorders are the most common class of inherited metabolic diseases that have been linked to NIHF. They are characterized by an abnormal build-up of various toxic materials in the body’s cells due to enzyme deficiencies. However, infantile-onset Pompe disease, an autosomal recessive inborn error of metabolism, hasn’t previously been associated with nonimmune hydrops fetalis.
University of Michigan investigators report what they believe to be the first patient with NIHF later diagnosed with infantile onset Pompe disease.
Around 37 weeks of pregnancy, doctors detected severe nonimmune hydrops fetalis. Until then, the pregnancy had concerns.
After his birth, the boy was found to have lymphatic fluid leaking into the space between both lungs and chest wall, a condition called bilateral chylothoraces, which resolved on its own.
An echocardiogram revealed the baby had a heart valve defect, which lead to dilation of the right portion of the heart and pulmonary hypertension. The heart continued to dilate and the organ’s ability to pump blood efficiency decreased.
Genetic testing showed the baby had two mutations in the acid alpha-glucosidase (GAA) gene, which cause Pompe disease. His GAA enzyme was barely active and urine glucotetrasaccharide levels were elevated, all consistent with a Pompe disease diagnosis. When GAA activity is low, a sugar molecule called glycogen accumulates inside cells, damaging organs and tissues throughout the body. Researchers did not specify at what age the patient was diagnosed with the metabolic disorder.
Following diagnosis, the boy started enzyme replacement therapy, the only effective treatment for Pompe. “The patient is currently 28 months old with significant improvement in cardiac status,” the investigators wrote.
They concluded that although infantile-onset Pompe disease is usually not considered as a cause for nonimmune hydrops fetalis, laboratories offering enzyme or molecular panels for abnormal collection of fluid in fetuses should include screening for Pompe disease, otherwise these children will keep being diagnosed later in life and experience disease progression.
“This case demonstrates the importance of considering IOPD as an etiology for infants who present with NIHF, particularly in states that have not included Pompe on the newborn screen. Laboratories offering enzyme or molecular panels for NIHF should include Pompe disease, otherwise delayed diagnosis will continue,” the authors wrote.