A delayed diagnosis that frequently occurs in Pompe disease (PD) may be due to the nonspecific symptoms in the disease, according to a new study published in BMJ Case Reports. This situation, in turn, causes late-onset of treatment which may be associated with higher mortality.

The team of researchers led by Senarathne described 2 case reports of patients from Sri Lanka. The first patient was a 4-month-old female whose parents complained about persistent nonproductive cough previously attributed to uncomplicated respiratory infections and failure to thrive.

During the physical examination, the positive findings included mild macroglossia, tachypnea, reduced breath sounds on the lower left lung, intercostal and subcostal recessions, nasal flaring, a systolic murmur, mild hepatomegaly, and reduced muscle tone in all extremities. Her perinatal history was without complications, although weight and length were below average, and she did not meet gross motor milestones at 4 months. The parents were second-degree consanguineous but claimed all family members were healthy. 

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The second patient was a 7-month-old male with a history of recurrent respiratory infections and gross-motor delays as early as 17-days-old. A systolic murmur was found at 1-month-old, and a cardiologist reported mild biventricular hypertrophy attributed to gestational diabetes that the mother presented. At 5 months, he had already required at least 3 hospitalizations due to respiratory distress and moderate hepatomegaly.

At 7 months his growth was below average, and the physical examination revealed coarse facial features, blue spots on the left forearm and bilateral ankles, tachypnea, hepatomegaly, and reduced muscle tone in all extremities. No family history of consanguinity was reported.

Both infants had type 2 respiratory failure, massive cardiomegaly seen in the chest X-rays, and ventricular hypertrophy, making PD the most likely diagnosis. Nonetheless, confirmatory tests were not available in the country, and samples to assess acid alpha-glucosidase (GAA) levels in India revealed low lysosomal GAA levels. Supportive medical care was administered while enzyme replacement therapy (ERT) was started; however, both infants died from cardiorespiratory failure before specific treatment could be initiated.

These cases exhibit the detrimental effects of a wrongful diagnosis. “Due to the rarity of PD and a variety of disorders with a similar presentation, the initial diagnostic workup may overlook PD, as observed in the index patients,” the authors said. “This may lead to a symptomatic management approach during initial presentations, which is detrimental in PD as irreversible muscle damage occurs with time.”

“Early initiation of treatment significantly improves the quality of life as the best motor outcome is achieved by introducing ERT before irreversible muscle damage caused by the buildup of lysosomal glycogen,” they concluded, emphasizing the importance of considering PD in patients with nonspecific symptoms that may be masking more serious diseases.


Senarathne U, Jasinge E, Viknarajah Mohan S, Waidyanatha S. Non-specificity of symptoms in infantile-onset Pompe disease may delay the diagnosis and institution of treatment. BMJ Case Rep. Published online February 22, 2022. doi:10.1136/bcr-2021-247312