Beta-mannosidosis

General Information (adopted from Orphanet):

Synonyms, Signs: MANSB
Lysosomal beta-mannosidase deficiency
Beta-mannosidase deficiency
Beta-mannosidosis
Number of Symptoms 37
OrphanetNr: 118
OMIM Id: 248510
ICD-10: E77.1
UMLs: C0342849
MeSH: D044905
MedDRA:
Snomed: 238047006

Prevalence, inheritance and age of onset:

Prevalence: 0.1 of 100 000 - PMID: 23588843 [IBIS]
Inheritance: Autosomal recessive
- PMID: 8859034 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Developmental anomaly of metabolic origin
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Lysosomal disease with hypertrophic cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Lysosomal storage disease with skeletal involvement
 -Rare bone disease
 -Rare genetic disease
Oligosaccharidosis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Rare hereditary metabolic disease with peripheral neuropathy
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Despite its residual activity, the p.Arg641His mutant enzyme is associated with a severe clinical presentation (PMID:19728872).

Symptom Information: Sort by abundance 

1
 (HPO:0001999) Abnormal facial shape Very frequent [Orphanet] Occasional [HPO:probinson] 10571005 IBIS 169 / 7739
2
 (HPO:0000503) Tortuosity of conjunctival vessels 3762648 IBIS 3 / 7739
3
 (HPO:0000365) Hearing impairment Very frequent [Orphanet] Frequent [IBIS] 71% (n=17) 18980795 IBIS 539 / 7739
4
 (HPO:0000718) Aggressive behavior 18980795 IBIS 109 / 7739
5
 (HPO:0000752) Hyperactivity 18980795 IBIS 140 / 7739
6
 (HPO:0003487) Babinski sign 18980795 IBIS 179 / 7739
7
 (HPO:0002167) Neurological speech impairment 10571005 IBIS 308 / 7739
8
 (HPO:0002069) Generalized tonic-clonic seizures 23588843 IBIS 96 / 7739
9
 (HPO:0002015) Dysphagia 23588843 IBIS 301 / 7739
10
 (HPO:0001250) Seizures Very frequent [Orphanet] Rare [HPO:probinson] Occasional [IBIS] 19% (n=21) 23588843 IBIS 1245 / 7739
11
 (HPO:0007108) Demyelinating peripheral neuropathy Rare [HPO:probinson] Rare [IBIS] 6% (n=17) 18980795 IBIS 8 / 7739
12
 (HPO:0002317) Unsteady gait 18980795 IBIS 45 / 7739
13
 (HPO:0002510) Spastic tetraplegia 18980795 IBIS 54 / 7739
14
 (HPO:0001249) Intellectual disability Frequent [IBIS] 76% (n=17) 18980795 IBIS 1089 / 7739
15
 (HPO:0001260) Dysarthria 18980795 IBIS 329 / 7739
16
 (HPO:0200134) Epileptic encephalopathy Rare [IBIS] 6% (n=17) 18980795 IBIS 42 / 7739
17
 (HPO:0001251) Ataxia 18980795 IBIS 413 / 7739
18
 (HPO:0001285) Spastic tetraparesis 18980795 IBIS 29 / 7739
19
 (HPO:0003393) Thenar muscle atrophy 8285582 IBIS 10 / 7739
20
 (HPO:0001014) Angiokeratoma Occasional [IBIS] 24% (n=17) 18980795 IBIS 5 / 7739
21
 (HPO:0001939) Abnormality of metabolism/homeostasis 23588843 IBIS 328 / 7739
22
 (HPO:0012066) Increased urinary disaccharide excretion 23588843 IBIS 2 / 7739
23
 (HPO:0001601) Laryngomalacia 23588843 IBIS 61 / 7739
24
 (HPO:0002205) Recurrent respiratory infections Very frequent [Orphanet] Frequent [IBIS] 35% (n=17) 18980795 IBIS 254 / 7739
25
 (HPO:0010307) Stridor 23588843 IBIS 19 / 7739
26
 (HPO:0002719) Recurrent infections 22369051 IBIS 107 / 7739
27
 (HPO:0001252) Muscular hypotonia 10571005 IBIS 990 / 7739
28
 (HPO:0001324) Muscle weakness 18980795 IBIS 859 / 7739
29
 (HPO:0007340) Lower limb muscle weakness 18980795 IBIS 61 / 7739
30
 (HPO:0012157) Subcortical cerebral atrophy 18980795 IBIS 3 / 7739
31
 (OMIM) Decreased beta-mannosidase activity in plasma, fibroblasts, and leukocytes 19728872 IBIS 1 / 7739
32
 (OMIM) Gilles de la Tourette syndrome (reported in 1 patient) 16401745 IBIS 1 / 7739
33
 (OMIM) Cytoplasmic vacuolization 17420068 IBIS 1 / 7739
34
 (HPO:0002059) Cerebral atrophy 18980795 IBIS 171 / 7739
35
 (HPO:0001334) Communicating hydrocephalus 23588843 IBIS 32 / 7739
36
 (HPO:0002120) Cerebral cortical atrophy 18980795 IBIS 187 / 7739
37
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 18980795 IBIS 949 / 7739

Associated genes:

MANBA;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
MANBA rs121434334 pathogenic RCV000001747.5
MANBA rs121434335 pathogenic RCV000001749.4
MANBA rs121434336 pathogenic RCV000001750.4

Additional Information:

Description: (OMIM) Beta-mannosidosis is an autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of lysosomal beta-mannosidase activity. The most severely affected patients show developmental delay and mental retardation, but there are differing levels of severity and ...
Clinical Description OMIM Wenger et al. (1986) described a 46-month-old boy with a severe deficiency in beta-mannosidase activity, whose parents had an intermediate level of enzyme consistent with autosomal recessive inheritance. Beta-mannosidase activity levels near zero were found in all available ...
Molecular genetics OMIM In 2 affected sibs from a Czech Gypsy family with beta-mannosidosis reported by Kleijer et al. (1990), Alkhayat et al. (1998) identified a homozygous null mutation in the MANBA gene (609489.0001).

In 2 patients with beta-mannosidosis, ...