Newborn examination for Pompe disease It is widely possible and could facilitate early treatment with better outcomes for children with a childhood disease, according to a new study from Italy – the largest of its kind in Europe.
Newborn screening, or NBS, involves screening babies soon after birth for genetic disorders such as Pompe disease.
In Italy, a newborn screening program for Pompe and related disorders was created in 2015. In this study, researchers shared their experiences during the program — and set goals for its future.
NBS evaluation in Italy
Over the course of seven years, dried blood spot samples were collected from 206,741 neonates. Using a chemical analysis technique called tandem mass spectrometry, the samples were evaluated for, among other factors, GAA enzyme activity.
Pompe disease due to mutations in the genetic coding for GAA.
Of all newborns screened, 39 infants (0.019%) tested positive at initial screen and were referred for confirmatory testing, including genetic analysis.
Three of these children were eventually diagnosed Infantile Pompe disease (IOPD), with all three diagnoses confirmed within the first two weeks of life. Two newborns had a prenatal diagnosis of heart disease characteristic of IOPD, while all three had elevated levels of markers of muscle damage on laboratory tests.
IOPD patients started Enzyme replacement therapy (ERT), namely Lumizim (alglucosidase alfa), between the fifth and the nineteenth day of life. In two of these patients, cardiac function stabilized a few months after ERT, and the infants showed age-typical locomotor development starting at about 1 year of age.
As of the study’s publication, these children were 3.5 and 1.5 years old. Both are still on ERT without problems, and have ‘age-appropriate motor development with no signs of cardiomyopathy’. [heart disease] And the normal biochemical test.”
The course of the third child was further complicated by the development of an immune response against ERT.
After receiving supportive anti-inflammatory therapy, this child was converted to AT-GAAIt is an experimental treatment given under compassionate use. Since this switch, the child’s heart function has remained relatively stable, and although his motor function is delayed compared to normal, he can walk by the age of 2.5 years.
Now at age 3.5, this child is able to walk, eat and breathe independently, although the researchers note that he has delayed language development and has shown difficulty with relationships.
Eight more children were diagnosed with late-onset Pompe disease (LOPD) after confirmatory testing. None of these babies showed signs of heart problems at birth, as is typical in LOPD.
These eight children are regularly assessed for development Pompeii symptoms. So far, with up to 5.5 years of follow-up, none of them have developed any symptoms yet, and none have yet started early recovery treatment.
The authors note that the guidelines address the management of confirmed IOPD cases and symptomatic LOPD cases.
However, they write “there is no consensus on the definition of ‘episodic’ LOPD.”
“These guidelines should be revised based on the new data available on LOPD cases identified through NBS programmes,” the researchers wrote. They particularly stressed the need for better guidance on how to manage LOPD patients who are not yet symptomatic.
In addition to these children, some family members of children diagnosed with NBS have also been diagnosed.
For example, two older siblings who were born before the launch of the NBS show were also found to have Pompe disease.
Our study, the largest reported to date in Europe, demonstrates this [Pompe] The scientists concluded that NBS is feasible and easily expandable to larger numbers of newborns in Italy.
The rest of the patients who were ultimately positive for NBS were not diagnosed with Pompe disease after confirmatory testing. Four of these children were found to be carriers of Pompe disease – meaning they would not have symptoms, but could pass a disease-causing mutation to their children.
Others have been found to have pseudo-deficient – a genetic variation known to cause a false positive on screen – mutations that are not expected to cause disease, or to have mutations of uncertain clinical relevance.
The researchers highlighted the relatively high number of false positive rates, as well as the lack of guidance for LOPD patients who may never develop symptoms, as issues that need to be addressed in the future.
The team concluded that “the high frequency of pseudomonas deficiency, ethical issues related to early diagnosis of LOPD, and the difficulty in predicting phenotypes based on biochemical parameters and genotypes, particularly in LOPD, need further study.”