Learning objectives

• Describe mucopolysaccharidoses
• Understand the anesthetic risk factors and complications associated with mucopolysaccharidoses
• Anesthetic management of a patient with mucopolysaccharidosis

Definition and mechanisms

• Mucopolysaccharidoses (MPS) are rare, inherited, lysosomal storage diseases characterized by deficiencies in different lysosomal enzymes involved in the metabolism of glycosaminoglycans (mucopolysaccharides)
• MPS causes an accumulation of glycosaminoglycans (mucopolysaccharides) in the brain, heart, liver, bone, cornea, and tracheobronchial tree
• Glycosaminoglycan accumulation in the upper airway results in hypertrophy of adenoids, tonsils, tongue (macroglossia), and laryngopharynx
• There are seven types and several subtypes of MPS, each with various clinical presentations → four broad categories
  • MPS I, II, and VII affect soft tissue storage and the skeleton with or without brain disease
  • MPS VI affects both soft tissues and the skeleton
  • MPS IVA and IVA are primarily associated with skeletal disorders
  • MPS III A-D are primarily associated with central nervous system disorders
• Autosomal recessive inheritance, except for MPS II, which is an inherited X-linked recessive disorder
• Patients with MPS often have a significantly shortened lifespan

Signs and symptoms, complications

• Damage to neurons
• Pain and impaired motor function resulting from compressed nerves or nerve roots in the spinal cord or peripheral nervous system
• Coarse facial features (flat nasal bridge, thick lips, and enlarged mouth and tongue)
• Short stature with disproportionately short trunk/torso (dwarfism)
• Abnormal bone size and/or shape (dysplasia) and other skeletal abnormalities
• Thickened skin
• Hepatosplenomegaly
• Hernias
• Carpal tunnel syndrome restricting hand mobility and function
• Recurring respiratory infections, obstructive airway disease, and obstructive sleep apnea (OSA)
• Heart disease, often involving enlarged or diseased heart valves
• Hyperactivity
• Depression
• Speech difficulties
• Hearing impairment
• Hydrocephalus 
• Corneal clouding, degeneration of the retina, and glaucoma → vision problems
• Intellectual disabilities, developmental delays, or behavioral problems

Treatment

• Surgery to drain excess cerebrospinal fluid from the brain
• Surgery to free nerves and nerve roots compressed by skeletal and other abnormalities
• Surgery to correct hernias
• Corneal transplants to improve vision in patients with significant corneal clouding
• Surgery to remove the tonsils and adenoids to improve breathing in patients with obstructive airway disorders and OSA
• Enzyme replacement therapy (MPS I, II, IVA, VI, and VII) to reduce non-neurological symptoms and pain

Anesthesia challenges

Anesthetic risk factors

• Hypopharynx
• • Hyperplasia of adenoids, tonsils, and pharyngeal tissue
  • Narrow due to redundant tissue
• Neck pathology
  • Cervical cord compression
  • Short neck
  • Atlantoaxial instability (only for MPS IV)
• Oral cavity
  • Macroglossia (large tongue)
  • Limited mouth opening
• Cardiac
  • Coronary disease
  • Valve disease
  • Heart failure
  • Significant arrhythmias
  • Pulmonary hypertension
• Respiratory
  • Restrictive lung disease
  • Obstructive lung disease, OSA
  • Breathing at closing capacity
  • Recurrent pulmonary infections
  • Pectus excavatum
  • Kyphoscoliosis
  • Narrow trachea
• Neurological
  • Potential developmental delay, uncooperative
  • Dural thickening can result in compressive myelopathy
  • Hydrocephalus
• Other
• • Hepatosplenomegaly
  • Hepatic dysfunction
  • Metabolic acidosis due to the inability to convert lactic acid to glycogen
  • Hemorrhagic diathesis due to platelet dysfunction

Anesthetic complications that may occur during anesthesia in patients with MPS

• Inability to ventilate or intubate
• Temporary airway obstruction → can cause negative pressure (potentially obstructive) pulmonary edema
• Complete airway obstruction (mostly during induction or at extubation) → can cause hypoxemia and cardiac arrest
• Post-intubation problems
• Stridor
• Lower airway collapse/infection
• Need for reintubation or tracheostomy

Management

Keep in mind

• MPS are multisystem diseases, but the airway is the main concern (53% difficult intubation, 23% failed intubation)
• All MPS types, except for MPS III, have facial and airway characteristics which may challenge anesthetic airway management

Suggested reading

• Clark BM, Sprung J, Weingarten TN, Warner ME. Anesthesia for patients with mucopolysaccharidoses: Comprehensive review of the literature with emphasis on airway management. Bosn J Basic Med Sci. 2018;18(1):1-7.
• Walker R, Belani KG, Braunlin EA, et al. Anaesthesia and airway management in mucopolysaccharidosis. J Inherit Metab Dis. 2013;36(2):211-219.