This page explains how newborn screening for MPS I works, what happens after a positive screen, and why follow up is especially urgent when a baby is likely to have severe MPS I-H.
What newborn screening does and does not do
Newborn screening is not a full diagnosis. It is a first test that looks for conditions where early treatment can change the outcome. For MPS I, the screening test measures IDUA enzyme activity in a dried blood spot. Babies with IDUA activity below a set cut-off are flagged for further testing.
A normal screening result makes MPS I very unlikely, although no test is perfect.
A positive screening result means the baby needs confirmatory tests, it does not mean that MPS I is already confirmed.
Screening can detect both severe MPS I-H and attenuated MPS I, as well as some babies with low IDUA due to pseudodeficiency who will never develop the disease.
Screening Flow
Heel prick sample
IDUA activity measured
If low: Second tier tests
If still concerning: Metabolic referral
First tier test
- IDUA enzyme activity is measured in dried blood spots using mass spectrometry or fluorimetric assays.
- If IDUA activity is within the normal range, the result is reported as screen negative.
- If IDUA activity is below the cut-off, the sample is screen positive and moves to further testing.
Second tier tests
Common second tier approaches include:
- Repeat IDUA activity with more specific methods.
- Measurement of glycosaminoglycan (GAG) markers in dried blood spots.
- IDUA gene sequencing to look for known pathogenic variants and pseudodeficiency alleles.
Referral for confirmatory testing
Babies who remain of concern after second tier testing are referred to a metabolic centre for full enzyme and genetic confirmation and clinical assessment.
What happens after a positive newborn screen
If your baby has a positive newborn screen for MPS I, you will usually be contacted by a specialist team or your local paediatrician. Although procedures vary, typical steps include:
You are contacted
- The team explains that the screen is not a diagnosis, but that further tests are needed.
Confirmatory tests
- Enzyme testing for IDUA in blood or white cells, urine GAGs, and IDUA gene analysis.
Specialist assessment
- A metabolic doctor examines your baby to look for very early signs of MPS I-H and to assess general health.
Discussion of severity
- Team discusses likely severity and treatment options based on test results.
What happens after a positive newborn screen
If your baby has a positive newborn screen for MPS I, you will usually be contacted by a specialist team or your local paediatrician.
You are contacted
- The team explains that the screen is not a diagnosis.
Confirmatory tests
- Enzyme testing, urine GAGs and IDUA gene analysis.
Specialist assessment
- A metabolic doctor examines your baby.
Discussion of severity
- Likely severity and treatment options are discussed.
Using newborn screening information to judge severity
- Type of IDUA variants found
- Level of enzyme activity
- Pattern of GAG markers
- Early clinical signs
◎ Benefits
- Earlier identification
- Timely HSCT planning
- Better family counselling
ⓘ Challenges
- False positives
- Severity prediction uncertainty
- Long-term follow-up needed
Further detail from the source pages
Further detail6 sections
Questions you can ask your team
If your baby has a positive MPS I screen, you may find it helpful to ask:
- Which tests have already been done, and what did they show?
- Which tests will be done next, and when will we get the results?
- Do the current results suggest severe MPS I-H, an attenuated form, or is it too early to tell?
- When will we meet a metabolic specialist and, if needed, a transplant team?
- How often will our baby be reviewed while we wait for more information?
- Can we speak to a genetic counsellor and, if desired, to another family who has gone through this process?
Managing a positive MPS I newborn screen
For clinicians receiving a positive screen from the laboratory, practical steps include:
- Contact the family promptly, ideally in person or by phone with enough time to explain the result calmly.
- Arrange early metabolic referral and follow local protocols for confirmatory testing (enzyme assay, urine GAGs, IDUA sequencing).
- Avoid over-reassuring or over-alarming; make clear that the screening test is a signal, not a diagnosis.
- If results strongly suggest severe MPS I-H, treat the situation as time sensitive and liaise with a transplant centre without delay.
- Ensure ongoing communication with the family while results are pending, and document all discussions.
Key points about newborn screening for MPS I
Newborn screening for MPS I measures IDUA activity in dried blood spots and can detect both severe MPS I-H and attenuated forms.
A positive screen is not a diagnosis; it triggers a series of confirmatory tests and clinical assessments.
Early identification of severe MPS I-H allows timely HSCT, which can prevent or reduce neurocognitive decline.
Many screen positive babies either do not have MPS I or have uncertain/attenuated forms, so algorithms that combine enzyme, GAG and genetic data are essential.
Long term follow up and clear communication are critical for both families and clinicians, particularly when severity is not immediately obvious.
How Hurler syndrome is diagnosed
Step by step diagnostic pathway
Early signs and red flags
What to look for if screening is not available
MPS I spectrum and severity
How severe MPS I-H differs from attenuated forms
Further detail — part 21 sections
Treatments and care
What happens after a confirmed diagnosis