Symptoms of alpha-mannosidosis
Signs and symptoms vary among people who have the condition. In general, affected individuals may have intellectual disabilities, coarse facial features, immunodeficiency, hearing impairment, and skeletal abnormalities.1,2
Characteristic facial features can include a large head, prominent forehead, rounded eyebrows, flattened nasal bridge, prognathism, widely spaced teeth, and a large tongue.4
Most common symptoms1,2,4,6-8
- Hearing impairment (>90%)
- Conductive and neurosensory
- Central nervous system (CNS) involvement
Cerebral atrophy and demyelination Cognitive impairment (>90%)- IQ 60-80
- Delayed development of speech
- Delayed motor and mental function
- Impairment of physical endurance
- Ataxia and muscular weakness (>60%)
- Psychiatric symptoms (≥45%)
- Ocular pathologies
- Tapeto-retinal degeneration
- Optic nerve atrophy
- Hurler-like features (>90%)
- Large head and prominent forehead
- Flattened nasal bridge
- Prognathism
- Short neck
- Pulmonary involvement
- Immunodeficiency
- Leading to frequent infections (middle ear, GI, and respiratory)
- Skeletal abnormalities (>90%)
- Genu valgus
- Joint contractures
GI=gastrointestinal.
Types of alpha-mannosidosis
At least 3 clinical types of alpha-mannosidosis (mild, moderate, and severe) have been suggested, classified according to the severity of the symptoms.4
Typically recognized after 10 years of age.
Notable features:
- Lack of skeletal abnormalities
- Very slow progression
The most common form, typically recognized before 10 years of age.
Notable features:
- Skeletal abnormalities
- Development of ataxia between ages 20-30
- Slow progression
Typically recognized at birth or soon after.
Notable features:
- Skeletal abnormalities
- Often leads to early death due to CNS involvement or myopathy
- Obvious progression
However, given the variety of mutations that have been documented, the broad range and severity of symptoms, and no link between particular mutations and symptomatology, the disease is considered clinically as a continuum, from mild to severe.1,2,4
Difficulties in diagnosing alpha-mannosidosis
Patients may present to doctors, nurses, or other healthcare providers at different times with a variety of symptoms, which makes alpha-mannosidosis a difficult condition to diagnose.1,2,4 The main symptoms can be shared with other lysosomal storage disorders, such as mucopolysaccharidoses.4
Generally, phenotypes of alpha-mannosidosis patients are not considered to be clearly distinguishable, so the prediction of the clinical course for an individual patient is very challenging.
The progressive nature of alpha-mannosidosis and its wide variability of clinical presentation requires a multidisciplinary approach.1,2,4 However, delayed diagnoses, a lack of diagnostics tools and guidelines, and the absence of specific treatment options have hindered the establishment of multidisciplinary teams. Early diagnosis remains critical, though, due to the nature of progressive diseases.3,4