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.
Almost 4-year-old boy shows the typical facial features of Hurler
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
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
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 ...