Mannosidosis, Alpha B

Clinical Characteristics

Ocular Features:

Many (probably most) patients have lens opacities and some have corneal opacities as well. Nystagmus and strabismus have been described. Pigmentary changes of a mottled nature can be present in the posterior pole and may be associated with retinal vessel attenuation and diminished ERG responses. Retinal thinning can be demonstrated. A mixture of hypo- and hyperautofluorescence is often visible. Mild optic atrophy has been seen. There is evidence for progressive visual loss, even late in life. Eyebrows appear thick.

Systemic Features:

Mannosidosis is a highly variable multisystem disorder. Onset may be in infancy but in other patients symptoms appear later in the first decade. Progression of disease is more rapid in individuals with early onset (type 3) with rapid mental, motor deterioration and early death. The characteristic coarse facial features usually are evident later in milder cases (types 1 and 2) that have mild or moderate intellectual disabilities. Regardless, mannosidosis is relentlessly progressive with mental deterioration and motor disabilities. Ataxia is a common feature. Dental anomalies (diastema), large ears, macroglossia, joint stiffness,, hepatosplenomegaly, enlarged head circumference, hearing loss (sensorineural), increased susceptibility to infections, dysarthria, and spondylolysis may be present.

Genetics

Alpha-mannosidoosis is an autosomal recessive lysosomal storage disorder resulting from mutations in the MAN2B1 [1] gene (19p13.2). There is another form of mannosidosis known as beta A (248510 [2]) caused by mutations in MANBA but ocular features have not been reported.

Treatment

Treatment Options:

Prompt treatment for infections is required and prophylactic vaccinations are indicated. All individuals should be seen annually and assistive devices such as wheel chairs and hearing aids prescribed when needed.

References

Article Title:

Retinal and optic nerve degeneration in α-mannosidosis [3]

Matlach J, Zindel T, Amraoui Y, Arash-Kaps L, Hennermann JB, Pitz S. Retinal and optic nerve degeneration in a-mannosidosis. Orphanet J Rare Dis. 2018 Jun 1;13(1):88. doi: 10.1186/s13023-018-0829-z.

PubMed ID:

29859105

Retinal dystrophy in 2 brothers with α-Mannosidosis [4]

Courtney RJ, Pennesi ME. Retinal dystrophy in 2 brothers with a-Mannosidosis. Arch Ophthalmol. 2011 Jun;129(6):799-802.

PubMed ID:

21670350

Late-onset retinal dystrophy in alpha-mannosidosis [5]

Springer C, Gutschalk A, Meinck HM, Rohrschneider K. Late-onset retinal dystrophy in alpha-mannosidosis. Graefes Arch Clin Exp Ophthalmol. 2005 Dec;243(12):1277-9.

PubMed ID:

16075219

Ocular findings in mannosidosis [6]

Arbisser AI, Murphree AL, Garcia CA, Howell RR. Ocular findings in mannosidosis. Am J Ophthalmol. 1976 Sep;82(3):465-71. PubMed PMID: 961797.

PubMed ID:

961797

Clinical manifestations of mannosidosis--a longitudinal study [7]

Yunis JJ, Lewandowski RC Jr, Sanfilippo SJ, Tsai MY, Foni I, Bruhl HH. Clinical manifestations of mannosidosis--a longitudinal study. Am J Med. 1976 Dec;61(6):841-8.

PubMed ID:

1008071