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A 60-minute webinar with Prof. Barbara Burton (clinical geneticist, Northwestern/Lurie Children's, Chicago), Prof. Joseph Muenzer (MPS specialist, University of North Carolina) and patient advocate Kristin McKay (Project Alive) on the early recognition and management of mucopolysaccharidosis (MPS) in primary care — the subtle signs, the role of newborn screening, and why early treatment matters. For primary-care physicians, paediatricians and specialists.
MPS disorders are progressive and multisystem, and the earliest signs are often things common in general practice — recurrent otitis media and upper-respiratory infections, hernias, chronic diarrhoea, developmental delay — so it is the combination that should prompt a search for a unifying diagnosis. Prof. Barbara Burton highlights the more specific clues (corneal clouding, thoracolumbar kyphosis, the gradual coarsening of facial features, progressive joint and shoulder stiffness) and notes that short stature is a later, not early, sign. Prof. Joseph Muenzer expands on the biology and the case for newborn screening: MPS comprises twelve enzyme deficiencies across eight clinical types, patients look normal at birth (except MPS VII) though storage begins in utero, and diagnosis rests on clinical suspicion supported by urinary GAG analysis and confirmatory enzyme and molecular testing. He reviews the treatment landscape — stem-cell transplantation (for severe MPS I under about two years) and intravenous ERT (for MPS I, II, IVA, VI, VII) — and stresses that ERT is far better at preventing disease than reversing it, so the earlier treatment begins the better, with newborn screening the way forward (now near-universal for MPS I in the US and expanding for MPS II). Kristin McKay brings the patient and family perspective, contrasting her brother — diagnosed with Hunter syndrome (MPS II) at about ten, after the typical diagnostic odyssey, and treated only once the disease had advanced — with her son, diagnosed before birth and treated from the first month with enzyme replacement and a stem-cell transplant at four months, who has shown few features of the disease. Her message: her son's early diagnosis is currently rare and will become possible for others only through newborn screening; and that even where a therapy does not treat the brain, there is always something that can be done — pain relief, range of motion, connection to resources and advocacy — that matters enormously to families. The panel closes on the hope offered by new therapies and the importance of primary-care recognition and referral.
After viewing this webinar, participants will be able to:
Many early signs are common in general practice — recurrent otitis media and upper-respiratory infections (often needing tubes several times), inguinal and umbilical hernias, chronic or recurrent diarrhoea, and developmental delay — so it is the combination of several that should prompt thinking about a unifying diagnosis. More specific clues include corneal clouding, a lump on the back (thoracolumbar kyphosis), the gradual coarsening of facial features, and progressive finger and shoulder stiffness. Short stature is a later sign, not an early one.
Because MPS is rare, heterogeneous and clinically subtle — the average paediatrician may see only one or two cases in a career — and because storage begins in utero while babies look normal at birth, so clinical diagnosis is usually made only after irreversible damage has begun. Newborn screening allows treatment before symptoms appear. In the US it is now near-universal for MPS I and expanding for MPS II (added to the recommended panel in 2022), with pilot and regional programmes for other types and in several countries.
Diagnosis rests on clinical suspicion supported by quantitative urinary GAG analysis (with species analysis by LC-MS/MS) and confirmed by lysosomal enzyme and molecular testing — straightforward for a geneticist once the child is referred, so the key is thinking of it. Treatment is haematopoietic stem-cell transplantation (for severe MPS I, best under about two years, and while development is still normal) and intravenous enzyme replacement therapy (for MPS I, II, IVA, VI and VII). ERT does not cross the blood-brain barrier and is far better at preventing disease than reversing it, so early treatment is essential.
It shows what timing means in real lives: a brother diagnosed with Hunter syndrome at about ten, after the usual diagnostic odyssey and treated only once the disease had advanced, compared with a son diagnosed before birth and treated from the first month (with a stem-cell transplant at four months) who shows few features of the disease. It also carries an important message: even when a therapy cannot treat the brain, there is always something worth doing — relieving pain, preserving range of motion, connecting families to resources and advocating for them — and any improvement, the 'inch-stones', matters enormously to families.
This content is intended for healthcare professionals only. The views expressed are those of the presenters and do not necessarily reflect those of Excellence in Pediatrics; their inclusion does not imply endorsement. The content is provided for educational purposes only and does not constitute medical advice or replace independent clinical judgement.