Mucopolysaccharidoses

Learning objectives

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

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

MPS type	Accumulated product	Enzyme	Gene/locus	Clinical manifestations
MPS I H	Heparan sulfate, dermatan sulfate	α-L-iduronidase	IDUA/4p16.3	Intellectual disability, facial dysmorphism, dwarfism, cardiomegaly, valvular disease, OSA, and hepatosplenomegaly
MPS I S
MPS I HS
MPS II	Heparan sulfate, dermatan sulfate	Iduronate-2-sulfatase	IDS/Xq28	Macroglossia, vocal cord enlargement, hydrocephalus, narrow airway, spinal stenosis, cardiomegaly, valvular disease, OSA, and hepatosplenomegaly
MPS III A	Heparan sulfate	Heparan N-sulfatase	SGSH/17q25.3	Dementia, seizures, language skills, deafness, blindness, enlarged tonsils, adenoids, and respiratory infections
MPS III B		N-acetylglucosaminidase	NAGLU/17q21.2
MPS III C		Heparan-α-glucosaminide N-acetyltransferase	HGSNAT/8p11.21
MPS III D		N-acetylglucosamine 6-sulfatase	GNS/12q14.3
MPS IV A	Keratan sulfate, chondroitin-6-sulfate	Galactose-6-sulfate sulfatase	GALNS/16q24.3	Short stature, atlantoaxial instability, odontoid hypoplasia, pectus carinatum, spine deformities, hepatomegaly, and restrictive lung disease
MPS IV B	Keratan sulfate	β-galactosidase	GLB1/3p22.3
MPS VI	Dermatan sulfate	N-acetylgalactosamine-4-sulfatase	ARSB/5q14.1	Short trunk, crouched stance, restricted joint movements, and heart disease
MPS VII	Heparan sulfate, dermatan sulfate, chondroitin-4,6-sulfate	β-glucuronidase	GUSB/7q11.21	Skeletal dysplasia, short stature, nerve entrapment, developmental delay, and hepatomegaly

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

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

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

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