Digital Microfluidics in Newborn Screening for Mucopolysaccharidoses: A Progress Report

Area of Science:

• Biochemistry
• Genetics
• Public Health

Background:

• Mucopolysaccharidosis type I (MPS I), also known as Hurler syndrome, is a rare genetic disorder.
• Newborn screening (NBS) for MPS I is implemented in select US programs using enzyme activity measurement in dried blood spots.
• Current screening methods include tandem mass spectrometry and digital microfluidic fluorometry (DMF).

Purpose of the Study:

• To detail the development and practical application of DMF for MPS I newborn screening in the USA.
• To assess the screen positive rate, follow-up procedures, and case classification for MPS I identified via DMF screening.
• To evaluate the effectiveness and cost-efficiency of DMF for MPS I NBS.

Main Methods:

• A questionnaire was distributed to US NBS programs utilizing DMF for MPS I screening.
• Data collected included screen positive rates, follow-up protocols, and confirmed MPS I case classifications (severe vs. attenuated).
• Analysis of over 1.3 million screened newborns' data.

Main Results:

• Over 1.3 million newborns were screened for MPS I using DMF.
• A screen positive rate of 0.173% (2094 infants) was observed.
• Confirmed diagnoses included five severe MPS I cases, two attenuated MPS I cases, and one undetermined phenotype.

Conclusions:

• DMF is an effective and economical method for MPS I newborn screening.
• High screen positive rates necessitate second-tier testing for accurate diagnosis.
• Preliminary data on DMF screening for MPS II and MPS III are also discussed.