Diagnostic Criteria

A proposed diagnostic algorithm for alpha-mannosidosis has been published, but clinical findings alone are not enough to establish the diagnosis because they overlap with clinical findings in other storage disorders .

Suggestive Findings

Alpha-mannosidosis should be suspected in individuals with the following clinical, radiographic, supportive laboratory, pathology, and family history findings.

Clinical features

• Macrocephaly with coarsening facial features. The facial features may progress to include:

• Prominent forehead

• Highly arched eyebrows

• Depressed nasal bridge

• Widely spaced teeth

• Macroglossia

• Prognathism

• Hearing loss (sensorineural or mixed)

• Frequent infections

• Developmental delay/ intellectual disability

• Ataxia

Source: GeneReviews — "Alpha-Mannosidosis"

Differential Diagnosis

Lysosomal storage disorders. The main clinical features in alpha-mannosidosis – intellectual disability, ataxia, coarse face, and dysostosis multiplex – may overlap with other lysosomal storage disorders (e.g., mucopolysaccharidosis type I and II). However, the distinctive clinical features associated with other lysosomal storage disorders, the availability of biochemical testing in clinical laboratories, and an understanding of their natural history should help in distinguishing between them.

Table 2.

Genes of Interest in the Differential Diagnosis of Alpha-Mannosidosis

Gene(s) | Disorder | MOI | Key Clinical Features of Disorder

Overlapping w/alpha-mannosidosis | Distinguishing from alpha-mannosidosis

ABCC9

KCNJ8

| Cant syndrome | AD | • Coarse facial features

• Thickened ribs

| • Heart defects

Source: GeneReviews — "Alpha-Mannosidosis"

Management Guidelines

No clinical practice guidelines for alpha-mannosidosis have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with alpha-mannosidosis, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Alpha-Mannosidosis: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measurement of weight, length/height, head circumference | To assess for poor growth /or macrocephaly

Hearing

| Audiologic eval assessment for middle ear effusions | Assess for both sensorineural conductive hearing loss.

Immunologic/

Rheumatologic

| Assess for signs/symptoms of frequent infections. | Consider referral to immunologist.

Clinical laboratory assessment for features of SLE | • To incl immunologic testing such as anti-nuclear antibodies anti-double-stranded-DNA antibodies

• Consider referral to rheumatologist.

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech-language eval

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

Alpha-Mannosidosis: Recommended Surveillance1

System/Concern | Evaluation | Frequency

Constitutional/

Poor growth

| Measurement of weight, length/height, head circumference, BMI;2 monitoring of growth pattern | At each visit

Consider endocrinology evals, incl hormonal lipid profiles | Regular intervals based on clinical features

Neurodevelopment

| Monitor developmental progress educational needs.3 | At each visit

Neurobehavioral/

Psychiatric

| Assessment for depression, sleep disturbances, anxiety, /or findings suggestive of psychosis (delusions, hallucinations)

Neurologic

| • Assess for new manifestations such ataxia gait abnormalities.

• Evaluate for asthenia4 signs/symptoms of communicating hydrocephalus.5

Musculoskeletal

| Assessment for muscle pain, joint aches, reduced range of motion, bone pain6

PT assessment of fine motor function, gross motor function, endurance (e.g., via the 6MWT, the 3MSCT, or the 9-hole peg test), ataxia (e.g., via the SARA), muscle strength tone | • Every 6-12 mos in childhood

• Annually in adults

• Consider DXA bone densitometry scan7 to assess for osteopenia/osteoporosis.

• Radiographs of hips/spine may be indicated.

| Every 2-5 yrs in children, adolescents, adults

Gastrointestinal

| • Monitoring for diarrhea

• Assessment of liver spleen size through physical exam

| At each visit

Source: GeneReviews — "Alpha-Mannosidosis"