Methylmalonic acidemia with homocystinuria, type cblF

General Information (adopted from Orphanet):

Synonyms, Signs: VITAMIN B12 LYSOSOMAL RELEASE DEFECT
COBALAMIN F DISEASE
COBALAMIN, DEFECT IN LYSOSOMAL RELEASE OF
VITAMIN B12 STORAGE DISEASE
METHYLMALONIC ACIDURIA DUE TO VITAMIN B12-RELEASE DEFECT
METHYLMALONIC ACIDEMIA AND HOMOCYSTINURIA, cblF TYPE
cblF
Combined defect in adenosylcobalamin and methylcobalamin synthesis, type cblF
Lysosomal membrane cobalamin transporter deficiency
Methylmalonic aciduria with homocystinuria, type cblF
Number of Symptoms 41
OrphanetNr: 79284
OMIM Id: 277380
ICD-10: E72.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 15 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Methylmalonic acidemia with homocystinuria
 -Rare genetic disease
 -Rare hematologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0012120) Methylmalonic aciduria 20 / 7739
2
 (HPO:0002156) Homocystinuria 12 / 7739
3
 (HPO:0003153) Cystathioninuria 5 / 7739
4
 (HPO:0010280) Stomatitis 8 / 7739
5
 (HPO:0000218) High palate 356 / 7739
6
 (HPO:0000206) Glossitis 9 / 7739
7
 (HPO:0011830) Abnormality of oral mucosa Very frequent [Orphanet] 47 / 7739
8
 (HPO:0000219) Thin upper lip vermilion 112 / 7739
9
 (HPO:0000286) Epicanthus 371 / 7739
10
 (HPO:0008551) Microtia 98 / 7739
11
 (HPO:0000369) Low-set ears 372 / 7739
12
 (HPO:0002066) Gait ataxia Frequent [Orphanet] 327 / 7739
13
 (HPO:0100543) Cognitive impairment Frequent [Orphanet] 230 / 7739
14
 (HPO:0001263) Global developmental delay 853 / 7739
15
 (HPO:0001254) Lethargy 104 / 7739
16
 (HPO:0002015) Dysphagia Very frequent [Orphanet] 301 / 7739
17
 (HPO:0000708) Behavioral abnormality Frequent [Orphanet] 212 / 7739
18
 (HPO:0004372) Reduced consciousness/confusion Very frequent [Orphanet] 73 / 7739
19
 (HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
20
 (HPO:0011968) Feeding difficulties 240 / 7739
21
 (HPO:0001508) Failure to thrive 454 / 7739
22
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
23
 (HPO:0000988) Skin rash Very frequent [Orphanet] 98 / 7739
24
 (HPO:0001889) Megaloblastic anemia Very frequent [Orphanet] 28 / 7739
25
 (HPO:0001876) Pancytopenia 89 / 7739
26
 (HPO:0001875) Neutropenia 83 / 7739
27
 (HPO:0001873) Thrombocytopenia 224 / 7739
28
 (HPO:0003524) Decreased methionine synthase activity 9 / 7739
29
 (HPO:0003223) Decreased methylcobalamin 11 / 7739
30
 (HPO:0003145) Decreased adenosylcobalamin 10 / 7739
31
 (HPO:0003286) Cystathioninemia 3 / 7739
32
 (HPO:0002160) Hyperhomocystinemia 10 / 7739
33
 (HPO:0002912) Methylmalonic acidemia 14 / 7739
34
 (HPO:0001252) Muscular hypotonia Very frequent [Orphanet] 990 / 7739
35
 (HPO:0001324) Muscle weakness 859 / 7739
36
 (HPO:0010547) Muscle flaccidity 466 / 7739
37
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
38
 (OMIM) Increased free cyanocobalamin in fibroblasts 2 / 7739
39
 (OMIM) Decreased activity of methylmalonyl-CoA mutase (MUT, 609058) 2 / 7739
40
 (OMIM) Impaired coordination 2 / 7739
41
 (OMIM) Reticulate pigmented skin abnormalities 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous disorder of cobalamin (cbl; vitamin B12) metabolism. The defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective ...
Clinical Description OMIM Rosenblatt et al. (1985, 1986) reported an infant girl with developmental delay, stomatitis, glossitis, seizures, and minimal methylmalonic aciduria responsive to vitamin B12. There was no megaloblastic anemia or homocystinuria. Like control cells, the patient's fibroblasts accumulated the ...
Molecular genetics OMIM In 12 unrelated patients with cblF, Rutsch et al. (2009) identified 5 different homozygous or compound heterozygous mutations in the LMBRD1 gene (612625.0001-612625.0003). A 1-bp deletion (612625.0001) was present in 18 of the 24 disease chromosomes, consistent with ...