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.
Mucopolysaccharidosis Type II (MPS II); Hurler-Hunter
Inborn error of metabolism first described by Charles A.
Hunter in 1917.
X-linked (male only). Gene map location is
Xq27.3-q28. Defective gene is iduronate 2-sulfatase (IDS).
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).
Typical phenotype. Increased urinary excretion of
dermatan and heparan sulfates. Specific enzyme defect demonstrable
(deficiency of iduronate 2-sulfatase activity in leukocytes and cultured
skin fibroblasts). Prenatal diagnosis available (defective enzyme activity
in cultured chorionic villi or amniocytes).
Two clinical variants—MPS IIA (severe form) and
MPS IIB (mild form)—represent the two ends of a wide spectrum of clinical
- MPS IIA: 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
- 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
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.
Children with Hunter syndrome most
frequently present with problems with airway management. The presence of
cardiomyopathy or obstructive sleep apnea further complicates anesthesia. In
general, anesthetic considerations are similar to those in Hurler syndrome
(see Hurler Syndrome). If tracheal intubation is predicted to be
difficult, spontaneous ventilation should be preserved until the airway is
secured and lung ventilation is confirmed.
Postoperatively, the patient should be carefully monitored for
episodes of airway obstruction. Opioids should be avoided and analgesia
provided by NSAIDs or regional techniques may be more appropriate.
The use of sedative medication preand postoperatively should ...