Hurler Syndrome

Genetically transmitted lysosomal storage disease resulting in accumulation of acid mucopolysaccharides in the central nervous system and peripheral tissues characterized by coarse facies (gargoyle-like), profound mental retardation, considerable hepatomegaly, hernias, enlarged tongue, skeletal disorders (kyphoscoliosis), dwarfism, and respiratory and cardiac impairment.

(Figure)

Alpha-L-Iduronidase Deficiency Syndrome; Dysostosis Multiplex; Dysostotic Idiocy; Johnie McL Disease; Hurler-Pfaundler Syndrome; Gargoylism; Lipochondrodystrophy; Mucopolysaccharidosis type IH; Pfaundler-Hurler Syndrome; Thompson Syndrome; Hurler-Scheie Syndrome.

Inborn error of metabolism of GAGs. First described in 1919 by Gertrud Hurler, a German pediatrician (1889-1965).

1:10,000-100,000 live births.

Autosomal recessive. Defective gene responsible for the production of alpha-l-iduronidase is located at chromosome 4p16.3. No sex predilection.

Deficiency of alpha-l-iduronidase leads to tissue accumulation of dermatan and heparan sulfates. The disease leads to severe disorders within the extracellular matrix, which is made up of several proteins and sugars, including proteoglycan, the catabolism of which yields dermatan and heparin sulfates.

Typical phenotype. Increased urinary excretion of dermatan and heparan sulfates. Deficiency of alpha-l-iduronidase activity in leukocytes and cultured skin fibroblasts. Prenatal diagnosis available (deficiency of enzyme activity in cultured chorionic villi or amniocytes, increased GAGs in amniotic fluid). Carrier detection possible using 4-methylumbelliferyl-α-iduronate.

Infants appear normal at birth but develop typical phenotype by the end of first year of life, including coarse facial features, large, deformed skull, short stature, kyphoscoliosis, multiple skeletal abnormalities, clouded corneas, hernias, and hepatosplenomegaly. As the disease progresses, there may be narrowing of the coronary arteries and thickening of the cardiac valves and myocardium leading to heart failure. The course of the disease is associated with a progressive deterioration with mental retardation. Death from cardiorespiratory failure commonly occurs in the early teens.

Assess cardiorespiratory status carefully and obtain appropriate investigations, for example, chest radiograph, echocardiogram. Assess airway and degree of cervical spine instability. Check medical history for evidence of airway obstruction during sleep. Treat intercurrent respiratory infections.

Children with Hurler syndrome frequently present difficulties with airway management that increases with age. About half of direct laryngoscopy and tracheal intubations are very difficult, and securing the airway may fail in 10%. The airway is compromised by accumulation of mucopolysaccharides in the soft tissues of the head and neck. Airway obstruction may occur during induction of anesthesia, and face-mask fit may be poor. The trachea may be narrowed or flattened, necessitating the availability of a range of endotracheal tube sizes. There is frequently severe limitation of movement of the cervical spine and restrictive lung disease. Progressive cardiac failure or pulmonary hypertension occur in some patients, further complicating management. The skin is thickened, and venous cannulation may be difficult. Because of the progressive ...