Fucosidosis

At a glance

Lysosomal storage disease resulting from nearly complete deficiency of alpha-L-fucosidase enzyme activity characterized by accumulation of lipids (glycosphingolipids) in the central nervous system (CNS) and peripheral tissues.

Synonyms

Alpha-L-Fucosidase Deficiency; Mucopolysaccharidosis F; Mucopolysaccharidosis Storage Disease F; FUCA Deficiency; Glycoproteinoses.

Classification

Many researchers believe there are two types of fucosidosis (Types I and II), which are determined by the severity of symptoms. Others theorize there are three types, with the age at onset and disease severity the determining factors.

• Fucosidosis Type I: Most severe form of the disease. The age at onset is the infancy period, and it may become apparent as early as age 6 months. Clinical symptoms include progressive deterioration of the brain and spinal cord, mental retardation, loss of previously acquired intellectual skills, and growth retardation leading to short stature. Dysostosis multiplex, coarse facial features, cardiomegaly, hepatosplenomegaly, and seizures complete the clinical picture.

• Fucosidosis Type II: Characterized by age at onset within the first few years of life and clinical symptoms that progress more slowly than in Type I. Other symptoms may be similar to Type I but are milder. The most noticeable feature distinguishing the two types is the appearance of angiokeratomas on the skin of individuals with Type II.

Incidence

Fewer than 100 cases have been reported. Equally distributed in males and females. Panethnic, but frequency is increased in populations of Italian and Spanish descent.

Genetic inheritance

Autosomal recessive. The gene (alpha-L-fucosidase) is mapped to chromosome 1p34 with a homologous site on chromosome 2. Seventeen mutation types have been reported.

Pathophysiology

Deficiency of alpha-L-fucosidase (a lysosomal enzyme that catalyzes removal of fucose residues from glycosphingolipids) results in accumulation and excretion of oligosaccharides and glycoproteins (mainly H antigen glycolipid).

Diagnosis

Based on history and physical findings. Increased sweat sodium chloride (infantile form) and urinary fucose-rich oligosaccharides, sphingolipids, and glycopeptides (about 22 glycopeptides) detected by thin-layer chromatography (no mucopolysaccharides). Enzyme assay of alpha-L-fucosidase in white blood cells or cultured fibroblasts. Prenatal diagnosis available (deficiency of alpha-L-fucosidase activity in cultured chorionic villi or amniocytes).

Clinical aspects

More severe cases (Type I or infantile form) are affected in the first year of life with mental and growth retardation, dysostosis multiplex, and coarse faces. Hepatosplenomegaly, cardiomegaly, seizures, and infections are variable. Death occurs around age 5 years. The milder form (Type II or juvenile form) has similar but less severe features, longer survival (early adulthood), and is distinguished from the infantile form with the presence of angiokeratoma.

Anesthetic considerations

The potential ...