Unusual symptoms complicate Pompe disease diagnosis: Report
Newborn's uncommon presentation highlight challenges doctors face
A newborn whose symptoms initially mimicked oxygen deprivation was ultimately diagnosed with Pompe disease, highlighting potential challenges in identifying the condition, according to a case report from Italy.
This was an uncommon presentation, according to researchers, who described the child’s symptoms, which included an enlarged heart and weak muscles. Based on the disease features, the investigators suspected the symptoms began before birth.
“These data may help clinicians recognize the characteristic features, enable early diagnosis, and initiate enzyme replacement therapy (ERT) promptly to decrease the morbidity and mortality associated with this disease,” researchers wrote.
The study, “An uncommon case of neonatal asphyxia associated with infantile-onset Pompe disease,” was published in the Italian Journal of Pediatrics.
Pompe disease symptoms may rarely begin before birth
Pompe disease is a metabolic disorder caused by mutations in the GAA gene, which contains instructions for cells to produce the acid alpha-glucosidase enzyme (GAA). As a result, the complex sugar glycogen accumulates in cells, reaching toxic levels that lead to cell damage.
ERT is the standard treatment approach for people with Pompe disease, providing the body with a working version of the GAA enzyme.
Symptoms can vary between individuals, but usually include muscle weakness and loss of muscle tone, as well as tongue, liver, or heart enlargement. In classic infantile-onset Pompe disease, symptoms typically appear within the first few months of life. More rarely, symptoms may begin before birth.
“The possibility of prenatal diagnostics has been described in the literature in cases of clinical suspicion or a suggestive family history, allowing for the initiation of in utero enzyme-replacement therapy,” the researchers wrote.
In the present report, they describe the case of a boy born in Pakistan without clinical suspicion of Pompe on ultrasound scans before birth. His parents were consanguineous, which means related by blood. The pregnancy was uneventful. No invasive screening tests were performed during pregnancy, even though the parents were aware of the risks associated with their consanguinity.
But after birth, “the newborn’s condition appeared immediately critical,” the researchers noted.
He showed a lack of muscle tone and was unusually pale. No heart activity was detected upon cardiac auscultation, ventilation support for breathing, cardiac massage, and three doses of adrenaline. After 15 minutes, the baby’s heart rate was detected, and he began to breathe independently.
Genetic testing revealed a mutation previously associated with Pompe
Physical examination was consistent with hypoxic-ischemic encephalopathy (HIE), a type of brain damage caused by poor oxygen flow. The clinical team lowered the boy’s body temperature, a standard therapy for HIE that slows metabolism and reduces the need for oxygen.
During the first day of life, laboratory tests indicated abnormally high levels of liver, heart, and tissue damage. A scan also showed the heart’s ventricles were abnormally large. During hospitalization, he continued to have poor muscle tone, became easily tired when sucking, and often kept his mouth open with his tongue protruding.
The child continued to require minimal breathing support for about 15 days, after which time his vital signs stabilized. Brain scans didn’t show signs of damage. Blood tests were normal, but urinary glucose tetrasaccharide, a biomarker of Pompe disease, remained persistently elevated.
Because inborn errors of metabolism can present during the neonatal period with … features that resemble HIE[,] an underlying metabolic disorder may go undiagnosed unless the clinician maintains a high index of suspicion and performs appropriate diagnostic testing.
Ultimately, genetic testing revealed a mutation previously associated with Pompe disease.
“Based on the clinical course observed at birth, we hypothesize a prenatal onset of Pompe disease in our patient,” the team wrote.
At 30 days, the newborn was transferred to a specialized hospital to start receiving ERT.
“Because inborn errors of metabolism can present during the neonatal period with … features that resemble HIE[,] an underlying metabolic disorder may go undiagnosed unless the clinician maintains a high index of suspicion and performs appropriate diagnostic testing,” the researchers wrote.
They suggested that clinicians perform appropriate tests and consider a metabolic disease such as Pompe when a newborn shows signs similar to HIE.
“In case of suspicion, it is necessary to promptly perform enzyme and genetic testing for early diagnosis and treatment,” the team added. “In the next few years, new gene therapy could emerge and completely change the prognosis for this disease.”
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