Newborn screening for MPS I and Hurler syndrome
In some countries, mucopolysaccharidosis type I (MPS I) is included in the national newborn screening programme. A small blood spot taken from a baby’s heel shortly after birth is tested for alpha L iduronidase (IDUA) activity. Low IDUA can be the first sign of MPS I, including severe Hurler syndrome (MPS I-H). Newborn screening can identify affected babies before symptoms appear, so that life-saving treatment, especially haematopoietic stem cell transplantation (HSCT), can be considered very early.
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.
First tier and second tier tests
Most newborn screening programmes use a tiered algorithm to improve accuracy and reduce false positives. Although protocols differ by country, they generally follow this pattern:
Screening Flow
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.
Reassurance: Many babies with a positive screen eventually turn out not to have MPS I or to have a milder form. It is understandable to feel anxious, but screening is designed to be cautious, so that no affected child is missed.
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.
The team explains that the screen is not a diagnosis.
Enzyme testing, urine GAGs and IDUA gene analysis.
A metabolic doctor examines your baby.
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
Advantages and current limitations
◎ Benefits
- Earlier identification
- Timely HSCT planning
- Better family counselling
ⓘ Challenges
- False positives
- Severity prediction uncertainty
- Long-term follow-up needed
For families
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?
For healthcare professionals
Managing a positive MPS I newborn screen
For clinicians receiving a positive screen from the laboratory, practical steps include:
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1Contact the family promptly, ideally in person or by phone with enough time to explain the result calmly.
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2Arrange early metabolic referral and follow local protocols for confirmatory testing (enzyme assay, urine GAGs, IDUA sequencing).
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3Avoid over-reassuring or over-alarming; make clear that the screening test is a signal, not a diagnosis.
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4If results strongly suggest severe MPS I-H, treat the situation as time sensitive and liaise with a transplant centre without delay.
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5Ensure ongoing communication with the family while results are pending, and document all discussions.