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At a glance

Genetically transmitted lysosomal storage disorder characterized by the accumulation of acid mucopolysaccharides (heparan and dermatan sulfates) in the central nervous system and peripheral tissues, affecting only male children and resulting in severe neurologic impairment.

Synonyms

Mucopolysaccharidosis Type II (MPS II); Hurler-Hunter Disease.

History

Inborn error of metabolism that was described by Charles A. Hunter in 1917.

Incidence

1:100,000 live births.

Genetic inheritance

X-linked (male only). Gene map location is Xq27.3-q28. Defective gene is iduronate 2-sulfatase (IDS).

Pathophysiology

Deficiency of iduronosulfate sulfatase, which catalyzes the breakdown of heparan sulfate (HS) and dermatan sulfate (DS), leading to tissue accumulation of these two mucopolysaccharides. The disease leads to severe disorders of the extracellular matrix, which is made up of several proteins and sugars including proteoglycan. The metabolism of proteoglycan yields mucopolysaccharides (also termed glycosaminoglycans [GAGs]). Depending on the severity of the deficiency of iduronosulfate sulfatase, accumulation of HS and DS is delayed (mild forms with residual enzyme activity) or rapidly severe (MPS IIA).

Diagnosis

Typical phenotype. Increased urinary excretion of dermatan and heparan sulfates. Specific enzyme defect is demonstrable (deficiency of iduronate 2-sulfatase activity in leukocytes and cultured skin fibroblasts). Prenatal diagnosis is available (defective enzyme activity in cultured chorionic villi or amniocytes).

Clinical aspects

Two clinical variants—MPS IIA (severe form) and MPS IIB (mild form)—represent the two ends of a wide spectrum of clinical severity.

  • MPS IIA: Severe form. Children develop coarse facial features (not visible at birth) with thick tongue and short neck, hernias, hepatosplenomegaly and skeletal deformities (pectus excavatum, kyphosis, pes cavus, progressive joint stiffening), growth retardation (dwarfism), obstructive airway disorders, pulmonary hypertension, and development of small nodules over the skin. Severe mental retardation and hearing loss. Cardiac involvement common (myocardial thickening, valvular dysfunction, coronary artery anomalies). Progression slower than in Hurler Syndrome, with survival to early adulthood common.

  • MPS IIB: Mild form. Normal intelligence or mild mental retardation, same skeletal disorders but at a reduced rate, carpal tunnel Syndrome, upper airway obstruction syndrome, corneal opacities, and progressive development of congestive heart failure and hearing loss. Life expectancy is up to the sixth decade.

Precautions before anesthesia

Assess cardiorespiratory status carefully and obtain appropriate investigations, for example, an echocardiogram. Assess airway (difficult direct laryngoscopy and tracheal intubation because of facial features, macroglossia, short neck). Check history of obstructive sleep apnea. The preparation for anesthesia must include proper airway management equipment for suspected difficult airway. It is mandatory to have the proper size laryngeal mask airway (LMA) before the procedure.

Anesthetic considerations

Patients ...

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