A small fat molecule that accumulates in the tissues of Fabry disease patients may be used as a biomarker for early diagnosis in the absence of recognizable clinical symptoms, according to a case report.
Globotriaosylsphingosine, or lyso-Gb3, is a fat molecule that is broke down by an enzyme called glucosidase. In Fabry disease this enzyme is absent or its activity is abnormally low, leading to the buildup of lyso-Gb3 in several tissues of the body.
Clinical manifestations of the disease have been reported as early as the age of 5, but little is known about disease progression during its asymptomatic stages.
Newborn screenings have significantly improved the diagnosis of these patients, and treatment with enzyme replacement therapy (ERT) have been shown to reverse the symptoms of Fabry disease. However, deciding when to initiate treatment may be a challenge in patients before the onset of symptoms.
A team at Boston Children’s Hospital led by Olaf Bodamer, MD and PhD, a specialist in genetics and genomics, reported the cases of two unrelated boys who were put on ERT before symptoms onset.
The results were presented in a poster titled “Early initiation of enzyme replacement therapy in pediatric Fabry disease” at the 14th WORLD Symposium held Feb. 5-9 in San Diego, California. The study’s abstract was published in the journal Molecular Genetics and Metabolism.
The boys, ages 3 and 5, had been diagnosed with classic Fabry disease, characterized by absent glucosidase activity due to mutations in the GLA gene. They had been screened for GLA mutations due to a family history of several males affected by this disorder.
When ERT was initiated, they only showed elevated lyso-Gb3 levels in the blood. Other lab tests were found to be within normal range.
The boys were treated with intravenous administration of 1 mg per kg body weight of algasidase beta every other week.
Of note, this enzyme replacement therapy was approved by the family’s medical insurance in both cases.
The relevance and liability of levels of the fat molecule lyso-Gb3 to diagnose and assess Fabry disease is still controversial, with several studies showing contrasting results.
Still, researchers believe lyso-Gb3 could be a biomarker for early asymptomatic stages of the disease, not only to help assess disease burden but also to determine the optimal timing for the start of treatment.
“A significant increase of plasma lyso-Gb3 levels over time or high levels at diagnosis should prompt the initiation of ERT in asymptomatic pediatric patients with Fabry disease,” the researchers concluded.