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Published on: April 16, 2013
Prospective Monitoring of Lyso-Gb1 on DBS Sample in Three Children Recognized at Newborn Screening for Gaucher
Claudia Rossi1,2, Daniela Trotta3, Rossella Ferrante1
1Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Insights
Gaucher disease (GD) screening in newborns shows that monitoring glucosyl-sphingosine (lyso-Gb1) levels can help determine enzyme replacement therapy (ERT) timing. A stable increase in lyso-Gb1 may indicate the need for ERT before symptoms appear.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Gaucher disease (GD) is an autosomal recessive lysosomal disorder.
- Neonatal screening for GD is expanding globally.
- Optimal timing for initiating enzyme replacement therapy (ERT) for GD remains unclear.
Purpose of the Study:
- To evaluate the utility of serial monitoring of blood glucosyl-sphingosine (lyso-Gb1) levels in newborns diagnosed with GD via screening.
- To assess if lyso-Gb1 trends can inform decisions about starting ERT in asymptomatic infants.
Main Methods:
- Three newborns diagnosed with GD through screening were monitored without ERT.
- Blood samples were collected on dried blood spots (DBS) at birth and every 4 weeks.
- Glucosyl-sphingosine (lyso-Gb1) levels were measured serially.
Main Results:
- All infants had elevated initial lyso-Gb1 levels.
- Two infants showed decreasing lyso-Gb1 levels within 4 months, normalizing by month 4.
- The third infant had a transient decrease, followed by stable levels; all remained asymptomatic with normal growth and blood counts.
Conclusions:
- A definitive lyso-Gb1 threshold for irreversible GD progression is not established.
- Hypothesize that a consistent upward trend in lyso-Gb1, rather than a single value, may warrant initiating ERT preemptively.
- Serial lyso-Gb1 monitoring shows potential for guiding ERT decisions in early-stage Gaucher disease.
Abstract:
Gaucher disease (GD) is an autosomal recessive lysosomal disease. Extended neonatal screening currently includes GD in several different regions. Decision on when to start enzyme replacement therapy (ERT) upon confirmed diagnosis or upon appearance of first clinical manifestation of the disease remains an unmet need. Methods: We report our preliminary experience in tightly monitoring blood levels of glucosyl-sphingosine (lyso-Gb1), on DBS at birth and then every 4 weeks, in the absence of ERT in three consecutive newborns identified for GD as part of a screening program. Results: Initial lyso-Gb1 values were above cut-off. In two cases, lyso-Gb1 levels showed a reduction during the first 3 months of life and, by month 4, they had reached a value lower than the upper normal value. In the case of the third child, after an initial drop to less than 50% of the initial value, lyso-Gb1 levels remained pretty stable at the following four time-points. At the time of writing, all remain free from any disease manifestation at the age of 20, 11 and 8 months, respectively, with normal physical growth and blood count; therefore, ERT has not been started yet. Conclusions: A specific threshold for lyso-Gb1 value to be considered as associated with non-reversible progression to disease is not yet defined. We hypothesize that a trend toward stable increase of this biomarker, confirmed at repeated evaluation, rather than a single threshold, could be convincing for starting ERT even before clinical manifestation of the disease.
