Newborn screening for lysosomal storage disorders in hungary

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Lysosomal storage disorders (LSDs) are rare but significant causes of illness and death, with a cumulative prevalence of 1:4,000.
• Early treatment for LSDs, including enzyme replacement and stem cell therapy, can improve prognosis and prevent irreversible organ damage.

Purpose of the Study:

• To assess the frequency of Fabry disease (FD), Gaucher disease (GD), Pompe disease (PD), and Niemann-Pick A/B (NPB) in newborns.
• To evaluate the feasibility and validity of tandem mass spectrometry (MS/MS) for LSD screening in a newborn population.

Main Methods:

• Screened 40,024 Hungarian newborns for FD, GD, PD, and NPB using tandem MS/MS.
• Conducted genetic confirmation for 120 samples with abnormal screening results after retesting.

Main Results:

• Identified a total of 17 LSD cases: 3 GD, 3 FD, 9 PD, and 2 NPB.
• Detected novel mutations in NPB and PD, raising questions about late-onset manifestations.
• Tandem MS/MS screening followed by genetic workup proved robust and feasible.

Conclusions:

• Newborn screening for LSDs using tandem MS/MS is a valid and feasible technology.
• Early diagnosis facilitates prompt treatment, but long-term clinical data are needed, especially for novel mutations.