A newborn boy has been diagnosed with infantile Pompe disease (IOPD) and sickle cell anemia (SCD) in the first case study to report two coexisting genetic disorders.
The boy received enzyme replacement therapy (ERT), standard Pompe therapy and regular blood transfusions to prevent heart damage from low red blood cell count due to SCD.
The case study, “Infantile Pompe disease complicated by sickle cell disease: case report and management considerationswas published in the journal Frontiers in Pediatrics.
Pump and sickle cell disease are caused by mutations in different genes
Pompe disease is caused by mutations in the GAA gene, which codes for acid alpha-glucosidase (GAA), an enzyme that breaks down a complex sugar molecule called glycogen. Such mutations result in the absence of GAA or a defective enzyme, leading to toxic buildup of glycogen and tissue damage, especially in muscle.
In people with IOPD, low muscle tone (hypotonia), swollen tongue (macroglossia), and cardiac enlargement can be seen before the age of 1 year.
SCD is caused by inherited mutations in the HBB gene, which contains instructions for making a component of hemoglobin, the protein that carries oxygen in red blood cells. Defective hemoglobin causes red blood cells to become stiff and sickle-shaped, making it difficult for them to pass through small blood vessels.
Blockage of blood vessels by sickled red blood cells can impede blood flow, leading to episodes of sudden, intense pain called vaso-occlusive crises. Sickle cells also die faster than they are made, leading to a shortage of red blood cells – a condition known as anemia, the most common symptom of SCD.
In this report, researchers from the Washington University School of Medicine in Missouri described the case of a newborn boy diagnosed with both IOPD and SCD.
“To our knowledge, no other reports of concurrent cases [occurring together] of these two disorders was found,” the researchers wrote.
The boy, of African American descent, was born at 39 weeks of pregnancy to two unaffected parents, each carrying the same mutation on one of their two HBB Genoa. Shortly after birth, he had difficulty breathing, which required non-invasive respiratory support and admission to the newborn intensive care unit.
Chest images revealed an enlarged heart and a physical exam showed the boy had low muscle tone and mild macroglossia. Echocardiogram images showed severe left ventricular hypertrophy, Pompe’s sign. Blood tests revealed elevated markers of muscle and heart damage, including pro-BNP, creatine kinase, and aldolase.
To our knowledge, no other reports of concurrent cases [occurring together] of these two disorders was found…. As more and more locations implement [newborn screening] for Pompe disease, it is expected that such cases will become more frequent
Newborn screening and genetic analysis confirm diagnosis of two diseases
Genetic analysis revealed two different mutations in each of the GAA genes, and a Newborn Screening Panel (NBS) revealed he had a GAA enzyme activity of 4%, which would normally be above 22%. Further testing confirmed low GAA activity and elevated urinary glucotetrasaccharide (Hex4), a biomarker of Pompe.
Regular infusions into the vein of Lumizyme (alglucosidase alfa) ERT were prescribed, which provided a working copy of the GAA enzyme.
Newborn screening also revealed the absence of a component of hemoglobin, consistent with sickle cell disease, and the diagnosis was confirmed by genetic analysis showing a HBB mutation.
Red blood cell transfusion was chosen as the boy’s primary treatment due to fears that chronic anemia would adversely affect heart function and that he would not be able to tolerate a vaso-occlusive crisis.
At 2 months of age, the boy showed further left ventricular enlargement in addition to global cardiac enlargement. As a result, he was treated with the blood pressure drug enalapril to prevent heart damage.
The viral infection of the lungs required three readmissions to hospital when the boy was three, five and six months old, with various respiratory supports. At the age of seven months, he was admitted with respiratory failure and received non-invasive respiratory support. Further echocardiogram showed resolved left ventricular hypertrophy and his heart function normalized.
At the time of the case report, he had received 10 blood cell infusions, remained on food assistance and continued to show low muscle tone. Despite excessive calorie intake to help him grow taller, he remained at less than 1% for weight and weight for height for boys his age.
“We presented a unique case of concurrent IOPD and ACS leading to complex initiation of ERT and the need for aggressive transfusion support to prevent cardiomyopathy [heart muscle disease] due to anemia,” the team concluded. “As more places implement NBS for Pompe disease, it is expected that such cases will become more common.”
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