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A practical, case-based webinar with Dr Dafne Horovitz (medical geneticist, Brazil) on how to avoid the misdiagnosis and delayed diagnosis of the mucopolysaccharidoses (MPS) in children — using real patient cases to teach the early signs and the radiological clues. For paediatricians and general practitioners.
Dr Horovitz works through a series of real cases in which MPS first mimicked common childhood problems — recurrent airway infections, allergy, asthma, hernias, growth delay — before the pattern became clear. Her central message is 'too many symptoms for one child': when a young child has multiple, apparently unrelated problems across systems (ENT, orthopaedic, developmental, cardiac), the differential should widen to include a rare genetic disorder like MPS. The early signs recur across her cases — coarse facial features and coarse hair, recurrent infections, claw hands, joint restriction, hepatosplenomegaly, umbilical or inguinal hernia, a lumbar gibbus, and slowed growth with a relatively large head — and she repeatedly returns to the radiological clues: dysostosis multiplex, the J-shaped sella, the 'epiphyseal encounter' (rendez-vous des épiphyses) of the metacarpals, hook-shaped vertebrae, and widened oar-/petal-shaped ribs. Her recurring plea: on a chest X-ray, look beyond the lungs to the bones. The cases span the MPS spectrum — severe Hurler (MPS I) diagnosed in infancy, MPS VI (Maroteaux-Lamy), and Morquio A (MPS IVA) — and several show striking, avoidable delays, including a child whose severe mitral valve was recognised as storage material only by the cardiac surgeon, and another picked up because the ophthalmologist noticed she 'looked different'. Diagnosis is confirmed with urinary GAGs, enzyme activity (the gold standard) and genetics (increasingly first, but always confirmed enzymatically). Early enzyme replacement therapy, and in severe cases haematopoietic stem-cell transplantation (often after ERT to improve the child's condition first), markedly changed outcomes — one Hurler girl treated from 22 months had, by six years, stable bone disease, resolved sleep apnoea and an IQ above expectation. Dr Horovitz stresses that the paediatrician is often the first, and sometimes only, line of defence, and that family history, consanguinity (all MPS are autosomal recessive except X-linked Hunter) and a cluster of red flags should prompt prompt referral.
After viewing this webinar, participants will be able to:
The combination — 'too many symptoms for one child'. When a young child has multiple, apparently unrelated problems across different systems (recurrent ENT infections, a hernia, orthopaedic or joint restriction, and slowed growth), the clinician should stop treating them as isolated issues and think of a rare genetic disorder like MPS. Individually these signs mimic common childhood illnesses; it is the cluster, put together over the whole clinical history like a puzzle, that leads to the diagnosis — which is why it rarely comes about by chance.
Look beyond the lung fields to the bones. Dr Horovitz's one take-home message is that a child with recurrent pneumonias will have had chest X-rays, and on those films the ribs may be widened — the oar-shaped (or petal-shaped) ribs of MPS. Together with hook-shaped vertebrae, a J-shaped sella and the 'epiphyseal encounter' of the metacarpals, these make up dysostosis multiplex. So on any chest film, assess the bones, not just the parenchyma — the skeletal signs may be the clue that a storage disorder is present.
By ordering the correct specific tests, because MPS is not found by chance. Suspicion (from the clinical pattern) prompts a urinary GAG screen; the gold standard for diagnosis is the enzyme activity assay, which identifies the deficient enzyme and the MPS type; and DNA-based testing (increasingly available through panels or newborn screening) supports it — but if you start from DNA, enzyme studies are still needed to confirm. Genotyping can lag, especially with intronic variants, so a typical clinical picture plus an abnormal enzyme activity is already the diagnosis.
Because MPS are progressive, incapacitating diseases with treatments of proven benefit, so early diagnosis lets clinicians modify the natural history. Even naming the disease helps the family, allows complications to be prevented, opens treatment or rehabilitation, and enables genetic counselling (recurrence risk is significant, as these are inherited). In Dr Horovitz's cases, treating young children — some in the first weeks of life — gave less bone disease than treating at one or two years, and one Hurler girl treated from 22 months had, by six years, stable bone disease, no sleep apnoea, and an IQ above expectation for severe MPS I.