What specialist should a child with suspected mucopolysaccharidosis (MPS) and macroglossia be referred to?

Referral for Suspected Mucopolysaccharidosis

A child with suspected mucopolysaccharidosis should be immediately referred to a metabolic specialist (biochemical genetics/metabolic disease center) for diagnostic confirmation, genetic counseling, and coordination of multidisciplinary subspecialty care. 1

Primary Referral Pathway

The metabolic specialist serves as the central coordinator and should be the first referral destination because:

• Diagnostic confirmation requires specialized enzyme testing (leukocyte enzyme activity assays) and genetic sequencing that metabolic centers are equipped to perform 1
• Treatment decisions are time-sensitive and depend on accurate phenotype prediction, which requires expertise in genotype-phenotype correlations 1
• Early intervention is critical for neurocognitive outcomes, particularly in severe forms where hematopoietic stem cell transplantation (HSCT) must occur before irreversible neurological damage 1

Essential Multidisciplinary Subspecialty Evaluations

Once the metabolic specialist confirms the diagnosis, the following subspecialists should be involved in comprehensive evaluation and ongoing management 1:

Immediate Surgical/Procedural Specialists

• Hematology/oncology - for HSCT evaluation and implementation in severe phenotypes (MPS I-H, severe MPS II) 1
• Pediatric surgery - for central venous catheter placement when enzyme replacement therapy (ERT) is initiated 1

Core Medical Subspecialists

• Cardiology - for echocardiography and electrocardiography to assess valvular dysfunction and cardiac complications 1
• Ophthalmology - for evaluation of corneal clouding, glaucoma, and vision impairment 1
• Otolaryngology - for management of recurrent otitis media, conductive hearing loss, upper airway obstruction, and macroglossia 1, 2
• Orthopedic surgery - for skeletal dysplasia, joint contractures, hip dysplasia, and spinal cord compression 1
• Pulmonology - for sleep-disordered breathing and respiratory complications 1
• Neurodevelopmental specialists - for cognitive assessment and monitoring developmental trajectory 1
• Pediatric neurosurgery - for communicating hydrocephalus and spinal cord compression management 1

Supporting Specialists

• Audiology - for periodic hearing assessments 1
• Genetics counseling - for family counseling and at-risk family member testing 1

Clinical Context: Macroglossia as a Presenting Sign

When macroglossia is present in suspected MPS:

• Macroglossia is a characteristic early sign of MPS, particularly in severe forms appearing in the first months of life, along with coarse facial features, hepatosplenomegaly, and skeletal abnormalities 3, 2
• Macroglossia in MPS causes functional complications including feeding difficulties, swallowing problems, sialorrhea, language alterations, and upper airway obstruction 2
• Otolaryngology involvement is essential for airway management and surgical evaluation if tongue reduction becomes necessary 1, 2

Critical Timing Considerations

The diagnostic delay in MPS remains problematic despite early signs being present 3. The urgency of referral depends on phenotype severity:

• Severe phenotypes (MPS I-H): HSCT must occur before significant developmental delay to preserve neurocognitive outcomes; engrafted survivors may still experience speech delay and learning disability even with early transplant 1
• Attenuated phenotypes: ERT can be initiated based on clinical judgment with regular monitoring every 3 months 1
• Unknown phenotypes: Require neurodevelopmental assessments every 3-4 months with HSCT evaluation "on hold" pending developmental trajectory 1

Common Pitfalls to Avoid

• Do not delay referral waiting for "classic" features to fully develop - early signs like hernias, recurrent upper respiratory infections, and organomegaly are nonspecific but their combination should prompt immediate evaluation 3
• Do not refer to individual subspecialists first - the metabolic specialist must coordinate care and determine phenotype before subspecialty interventions 1, 4
• Do not assume normal early development rules out severe disease - patients typically appear normal at birth with onset during early childhood 5
• Routine newborn screening is not yet universally available for all MPS types, making clinical recognition by pediatricians critical 4