Alpha-mannosidosis is an autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of lysosomal alpha-mannosidase activity. The disorder shows a wide range of clinical phenotypes, from a severe infantile form (type I), which is fatal at less than 3 to 8 years of age, to a less severe juvenile- or adult-onset form (type II), which ultimately shows progressive neurologic degeneration. - Wide phenotypic variability. Alpha-mannosidosis is caused by mutation in the gene encoding alpha-mannosidase, class 2B1 (MAN2B1) (MIM.609458).
Synopsis
growth retardation in severe cases
macrocephaly
Ffat occiput
coarse facial features
broad forehead
frontal bossing
midface hypoplasia
prognathism
sensorineural deafness
large ears
epicanthal folds
heavy eyebrows
lenticular ’spoke-like’ opacities
retinal degeneration in adult patients, progressive
impaired smooth pursuit in adult patients
nystagmus in adult patients
flat nose
macroglossia
gingival hypertrophy
widely-spaced teeth
pectus carinatum
thick, undertubulated ribs
hepatomegaly
splenomegaly
inguinal hernia (less common)
dysostosis multiplex
thickening of the calvaria
abnormal vertebral bodies (ovoid, flat, beaked)
increased vertebral height
thoracolumbar gibbus deformity
spondylolithesis
bowed femurs
hypertrichosis
Low anterior hairline
anterior hair whorl
heavy eyebrows
delayed psychomotor development
mental retardation from rapid mental regression
hypotonia
impaired speech
nerve cells show ballooning with membrane-bound vesicles with reticulogranular pattern
corticospinal tract disease in lower limbs (in adulthood)
spinocerebellar tract disease in lower limbs (in adulthood)
gait ataxia
limb ataxia
spasticity
extensor plantar responses
dysarthria
hyperreflexia
nystagmus
impaired smooth pursuit ocular movements
MRI shows cerebellar atrophy (in adulthood)
white matter changes may occur (in adulthood)
vacuolated lymphocytes in blood
recurrent bacterial infections
recreased serum immunoglobulin
LABORATORY
Increased urinary mannose-containing oligosaccharides
Decreased lysosomal alpha-mannosidase activity in plasma and leukocytes
Types
Type I is infantile-onset, severe, death usually by age 3 to 10 years
Type II is less-severe, juvenile- or adult-onset
Etiology
Alpha-mannosidosis is caused by mutation in the gene encoding alpha-mannosidase, class 2B1 (MAN2B1) (MIM.609458).