Adult onset leukodystrophy

Gene: MAN2B1

Red List (low evidence)

Comment on list classification: There is only one family with white matter abnormalities confirmed in adulthood. All other reported cases with white matter abnormalities detected by MRI are during childhood/ adolescence.

Created: 30 May 2023, 2:32 p.m. | Last Modified: 30 May 2023, 2:32 p.m.

Panel Version: 3.6

PMID:15534274 reported that MRI from three adult siblings with alpha-mannosidosis (AM) showed cerebellar atrophy and periventricular white matter changes.

PMID:26212233 reported that five of ten patients who have had MRI from the cohort of 34 patients with AM had occipital white matter signal abnormalities. However the age of these patients ranged from 7 to 17 years.

PMID:33317989 reported cerebral white matter signal abnormalities in 11 (85%) out of 13 untreated AM patients. In addition, cortical atrophy (62%), corpus callosum thinning (23%) and enlargement of perivascular spaces in white matter (38%) was observed. The age of onset (first symptom) of AM ranged from neonatal period to 4 years. However, four patients were currently adults with MRI taken during their adulthood.

This gene has been associated with alpha-mannosidosis in both OMIM (MIM #248500) and Gene2Phenotype ('Definitive' rating).

Created: 30 May 2023, 1:40 p.m. | Last Modified: 30 May 2023, 2:27 p.m.

Panel Version: 3.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mannosidosis, alpha-, types I and II, OMIM:248500

Publications

• 15534274
• 26212233
• 33317989

Green List (high evidence)

White matter changes may occur in adulthood.
Sources: Expert list

Created: 21 Jun 2020, 6:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mannosidosis, alpha-, types I and II, MIM# 248500

Variants in this GENE are reported as part of current diagnostic practice