Lysosomal glycoprotein storage disease with mental
retardation, hearing loss, and recurrent infections (upper or lower
respiratory tract, and gastrointestinal tract). Other clinical features include
coarse face, prominent forehead, prominent jaw, diffuse dysfunction of the
brain, severe ataxia, deafness, scoliosis, rheumatoid arthritis, hypotonia,
and muscle pain. Two types are described: α and β. α-Mannosidosis displays clinical heterogeneity, ranging from very serious to
very mild forms. β-Mannosidosis causes a severe disorder that affects
the peripheral and central nervous systems.
Lysosomal Mannosidosis Deficiency Syndrome.
First reported in 1967 by Oeckerman in Lund, Sweden, who
described a boy affected with mental retardation, increased tissue total
mannose concentration, and susceptibility to infection.
Rare; approximately 100 cases of α-mannosidosis
and 10 to 15 cases of β-mannosidosis have been described. Found in
all ethic groups in Europe, America, Africa, and Asia.
Autosomal recessive genetic disorder, 2.5:1
male preponderance. The α-mannosidase gene maps to chromosome
19p13.2-q12. The β-mannosidase gene is located at chromosome 4q22-25.
Prenatal diagnosis is possible.
α-Mannosidosis is a disorder of
glycoprotein catabolism associated with abnormal levels and excretion of
mannose-rich oligosaccharides, caused by a deficiency of its catabolic
enzyme α-mannosidase. β-Mannosidosis results from β-mannosidase deficiency with an increase in the corresponding
oligosaccharide. Both enzymes are located in the lysosomes.
Usually made by measuring enzyme activity in white blood
cells and eventually by measuring certain substances in urine. Increased
urinary oligosaccharides as measured by thin-layer chromatography confirms
the type. Measuring activity in lymphoblasts correlates with severity.
Pathology shows multiple vacuoles in lymphocytes and hepatocytes. Clinical
history and physical findings are considered important in the diagnosis.
Facies: The very typical facial
characteristics of mannosidosis are a coarse face, a prominent forehead, a
flattened nasal bridge, a small nose, and prominent jaw. Cerebral
symptoms: The disease causes a diffuse dysfunction of the brain
characterized by delayed early landmarks of neural development and severe
ataxia. Hearing problems: Central and peripheral deafness. Immunodeficiency: Recurrent infections are a main feature of the
disease. These infections are in the upper or lower respiratory tract, middle
ear, or gastrointestinal tract. Skeletal: Scoliosis, rheumatoid
arthritis, ataxia. Muscular: Muscular pain and weakness, which is
caused by accumulation of storage material in the muscle and usually
contributes to the immobilization of the patient.
α-Mannosidosis: Type I or severe infantile phenotype (onset between 3 and 12 months)
includes rapid, progressive mental retardation, coarse facies resembling
mucopolysaccharidosis, hepatosplenomegaly, dysostosis multiplex, recurrent
bacterial infections with death between 3 and 12 years. Type II or
juvenile-adult phenotype (onset between 1 and 4 years) is milder and slowly
progressive with survival into adulthood. Other clinical features include spastic
paraplegia (vertebral bodies abnormalities) and pancytopenia. In both types,
deafness, cataracts, corneal opacifications, and vacuolated lymphocytes are
present. Recurrent infections could be caused by a defect in leukocyte
chemotaxis. Dysostosis multiplex causes skeletal dysplasia, ovoid
configuration or flattening of the vertebral bodies, and kyphosis.