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“We hope that when the paediatrician sees the physical findings, and if the radiologist gets some X-rays, [that] they can say that these vertebrae don’t look normal [and] we need to send this child to the geneticist.” – Dr. Paul Harmatz

ENT in MPS: key to early suspicion and long-term care

Otolaryngology plays a critical role in MPS diagnosis

Ear, nose and throat (ENT) manifestations are commonly seen in individuals with mucopolysaccharidosis (MPS) and are often among the first symptoms to appear.1 Common manifestations include, but are not limited to, adenotonsillar hypertrophy, frequent infections of the upper airway and hearing loss.1,2

Delayed diagnosis can lead to:

  • Severe multisystemic complications1,4
  • Irreversible or end-organ damage1
  • Delayed treatment3
  • Lack of access to disease-specific management, with concomitant increase in risk of surgical mortality8-12
Signs and symptoms are unpredictable and clinically heterogeneous across and within MPS disorders, making diagnosis challenging. Patients may exhibit non-classical and/or classical signs of MPS, as well as rapidly or slowly progressing disease.3-7

Suspect, refer and rule out MPS

Because of emerging knowledge and therapeutic options, otolaryngology has opportunities to positively impact the lives of patients and families living with MPS through early identification, which can enable disease-specific management and access to available therapies. Be aware of signs and symptoms to expedite early intervention.

ENT and respiratory symptoms are common and can present in isolation or in combination with other symptoms. Maintaining a high index of suspicion for ENT manifestations may be a key trigger for early diagnosis of MPS and timely access to treatment.

  • In a cohort study of patients with MPS evaluated at a paediatric medicine department (Naples, Italy; June 1999 to June 2009), the vast majority (90%) of patients (N=20) had ENT manifestations2
  • In this cohort, the median age of presentation to an otolaryngologist was 12 months and median age at diagnosis was 3 years. This delay in diagnosis indicates there may be a significant opportunity to reduce time to diagnosis within this clinical setting2
  • Ten patients (50%) underwent ENT surgery as follows: adenotonsillectomy (5 patients, 25%), adenoidectomy (3 patients, 15%), tonsillectomy (2 patients, 10%), insertion of middle ear ventilation tubes (3 patients, 15%), tracheotomy (1 patient, 5%) and exeresis of vocal cord polyps (1 patient, 5%)2

Any number of ENT symptoms, especially if coupled with other systemic signs and symptoms, should prompt referral to a geneticist or metabolic centre.9,14 Along with the common ENT and respiratory signs, these additional features should also raise your index of suspicion for MPS:7

  • Coarse facial features
  • Enlarged head and tongue
  • Irregularly shaped teeth

Take a deep dive into signs and symptoms that should elevate your suspicion of MPS

Presentation and disease progression are unpredictable, multisystemic and variable across and within MPS disorders, making diagnosis challenging.9

Delayed diagnosis is common and it can have devastating consequences for your patients. Early identification of signs and symptoms across systems can be critical to early and accurate diagnosis. Become familiar with the diverse signs and symptoms of MPS that may present in your department.3,8

How else might you see MPS?

Patterns of signs and symptoms should elevate your clinical suspicion of MPS

Regardless of the clinical setting, there are overt and generally observable signs that should raise your suspicion. Upon further examination, additional symptomatology may be discovered through speciality-specific targeted clinical assessments, laboratory findings and patient history. This division is illustrated below.

Signs and symptoms of MPS1-5,7,9,13,15-24


General features

  • Abnormal gait
  • Bone dysplasia
  • Claw hands
  • Coarse facial features
  • Joint pain
  • Macrocephaly
  • Pectus carinatum
  • Reduced endurance/exercise intolerance
  • Short stature/growth retardationa

Features revealed by speciality-specific assessment

  • Abnormal gait
  • Bone deformities
  • Dysostosis multiplex
  • Genu valgum
  • Joint involvement (contractures, joint laxity) without inflammation
  • Spinal subluxation


General features

  • Decreased joint mobility
  • Hip stiffness and pain
  • Joint pain
  • Joint stiffness or laxity

Features revealed by speciality-specific assessment

  • Carpal tunnel syndrome
  • Joint involvement without joint swelling or erosive bone lesions

Ear, nose and throat

General features

  • Conductive and/or sensorineural hearing loss
  • Enlarged tongue
  • Recurrent otitis media

Features revealed by speciality-specific assessment

  • Abnormal epiglottis
  • Depressed nasal bridge
  • Hypertrophic adenoids
  • Hypertrophic tonsils
  • Middle ear mucus
  • Narrowing of supraglottic and infraglottic airway
  • Ossicular malformation
  • Recurrent and excessive rhinorrhea
  • Recurrent otitis media
  • Tracheal thickening/compression
  • Tubular obstruction
  • Tympanic membrane thickening


General features

  • Cataracts
  • Diffuse corneal clouding
  • Glaucoma

Features revealed by speciality-specific assessment

  • Amblyopia
  • Corneal clouding with characteristic ‘ground glass’ appearance
  • High hyperopia
  • Hypertelorism
  • Optic nerve abnormalities (swelling and atrophy)
  • Peripheral vascularisation of the cornea
  • Progressive pseudo-exophthalmos
  • Reduction in visual acuity
  • Retinopathy
  • Strabismus


General features

  • Behavioural abnormalities (typically not present in MPS IVA and VI)
  • Developmental delay (typically not present in MPS IVA and VI)
  • Hearing impairment
  • Seizures (typically not present in MPS IVA and VI)

Features revealed by speciality-specific assessment

  • Arachnoid cysts (typically not present in MPS IVA and VI)
  • Brain atrophy (typically not present in MPS IVA and VI)
  • Carpal tunnel syndrome
  • Cervical cord compression/myelopathy/subluxation
  • Enlarged perivascular space
  • Hydrocephalus
  • Odontoid dysplasia
  • Papilledema/optic atrophy
  • Sensorineural deafness
  • Signal-intensity abnormalities
  • Spinal canal stenosis
  • Ventriculomegaly


General features

  • Reduced endurance/exercise intolerance

Features revealed by speciality-specific assessment

  • Pulmonary hypertension
  • Thickened, regurgitant or stenotic mitral or aortic valves in presence of left ventricular hypertrophy
  • Tricuspid regurgitation


General features

  • Reduced endurance/exercise intolerance
  • Sleep apnoea

Features revealed by speciality-specific assessment

  • Obstructed upper and lower airways (bronchial narrowing, narrowing of supraglottic and infraglottic airway)
  • Progressive reduction in lung volume
  • Respiratory infections
  • Sleep disorders (OSAHS and UARS)


General features

  • Abdominal pain
  • Constipation
  • Hepatosplenomegaly
  • Hernias
  • Loose stools

Features revealed by speciality-specific assessment

  • Hepatosplenomegaly


General features

  • Abnormal buccal surfaces
  • Dentinogenesis imperfecta
  • Hypodontia
  • Pointed cusps
  • Spade-shaped incisors
  • Thin enamel

Features revealed by speciality-specific assessment

  • Abnormal buccal surfaces
  • Thin enamel

aSkeletal involvement and short stature may be less overt in some patients.

Otolaryngology can play a key role in identifying individuals with MPS and appropriate patients should be referred to a geneticist or metabolic centre for definitive diagnosis and, when available, initiation of treatment.9

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Early investigation leads to early intervention.
Avoid delay.

Stay informed about the latest updates and information about MPS.

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