Genetic test flags Pompe disease in expectant father with no symptoms
Prenatal counseling reveals LOPD, prompting new guidance for family's health
A man was diagnosed with late-onset Pompe disease (LOPD) after prenatal genetic counseling, even though he exhibited no symptoms.
“This example stresses the importance of pretest consultation and the relevance of clinical and ethical implications during prenatal genetic testing for the whole family group,” scientists wrote.
His condition was described in “Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction,” which appeared in Frontiers in Genetics.
In Pompe disease, mutations in the GAA gene result in low activity of acid alpha-glucosidase, an enzyme needed to break down a sugar called glycogen. Too much glycogen is toxic, particularly to muscle cells, which use glycogen as a source of energy. As a result, patients develop muscle weakness and other symptoms.
In LOPD, symptoms begin after 1 year of age. Usually, when appearing later in life, symptoms tend to be less severe, and the disease progresses more slowly. However, symptoms of LOPD are highly variable between patients.
Wife was 4 months pregnant during prenatal genetic counseling
The case study described a 33-year-old man in Italy who was diagnosed with Pompe disease after undergoing prenatal (parental) counseling along with his wife, who was four months pregnant.
Genetic screening revealed he carried two copies (homozygous) of a mutation called IVS1-32-13T>G in the GAA gene, meaning he had inherited it from both parents. This is consistent with a diagnosis of LOPD, the investigators noted. Approximately 50 patients have been described with such an IVS1 defect in the scientific literature, and those who carry it in both GAA gene copies may remain asymptomatic.
“Overall, findings collected on IVS1 homozygous patients suggest that this genotype [genetic makeup] is not associated with a severe course of the disease,” the researchers wrote.
The man’s wife had no GAA gene mutations, which means the fetus is a disease carrier with a mutation in the gene copy inherited from the father.
The man had no neuromuscular symptoms (muscle weakness, muscle pain, or cramps) and no reported limitations to his daily life. Heart and lung tests were normal, as were the blood levels of a biomarker of muscle damage.
At the molecular level, the mutation led to reduced activity of the acid alpha-glucosidase enzyme in the patient and, to a lesser extent, in his parents.
Because the man had no symptoms, enzyme replacement therapy was not recommended. Still, his clinicians suggested he adhere to the follow-up schedule they propose for LOPD-diagnosed newborns, with biomarker evaluations every six to eight months and yearly monitoring of heart and lung status. Skeletal muscle MRI is to be performed every two years if the man’s condition remains stable.
“ERT starting is likely not necessary for adult patients while it should be evaluated on symptomatic pediatric cases. The decision on when to start ERT in pre-symptomatic LOPD patients is a treatment dilemma in the balance between the expected relevant benefits in terms of muscle preservation and medical and economical aspects,” the scientists wrote.
The findings also have implications for genetic counseling. “Incidental parental findings during prenatal and reproductive genetic screening and testing have implications for reproductive decision making but also, as in this case, for parental health guidance and management,” the investigators concluded.
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