Methylmalonic acidemia with homocystinuria, type cblJ

General Information (adopted from Orphanet):

Synonyms, Signs: MAHCJ
Methylmalonic aciduria with homocystinuria, type cblJ
Combined defect in adenosylcobalamin and methylcobalamin synthesis, type cblJ
Number of Symptoms 53
OrphanetNr: 369955
OMIM Id: 614857
ICD-10: E71.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 5 cases - PMID: 28572511 [IBIS]
Inheritance: Autosomal recessive
- PMID: 28572511 [IBIS]
Age of onset: Neonatal
Infancy
- PMID: 28572511 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Methylmalonic acidemia with homocystinuria
 -Rare genetic disease
 -Rare hematologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0012592) Albuminuria 28572511 IBIS 6 / 7739
2
 (HPO:0005518) Erythrocyte macrocytosis 28572511 IBIS 13 / 7739
3
 (HPO:0005599) Hypopigmentation of hair 28572511 IBIS 38 / 7739
4
 (HPO:0010550) Paraplegia 28572511 IBIS 10 / 7739
5
 (HPO:0000488) Retinopathy Frequent [IBIS] 28572511 IBIS 75 / 7739
6
 (HPO:0009830) Peripheral neuropathy Frequent [IBIS] 28572511 IBIS 206 / 7739
7
 (HPO:0000505) Visual impairment 28572511 IBIS 297 / 7739
8
 (HPO:0100502) Vitamin B12 deficiency Very frequent [IBIS] 28572511 IBIS 4 / 7739
9
 (HPO:0008872) Feeding difficulties in infancy 28572511 IBIS 153 / 7739
10
 (OMIM) Elevated plasma propionylcarnitine 28572511 IBIS 2 / 7739
11
 (HPO:0008689) Bilateral cryptorchidism 38 / 7739
12
 (HPO:0012120) Methylmalonic aciduria Very frequent [IBIS] 28572511 IBIS 20 / 7739
13
 (HPO:0002156) Homocystinuria Very frequent [IBIS] 28572511 IBIS 12 / 7739
14
 (HPO:0000028) Cryptorchidism rare [HPO:skoehler] 347 / 7739
15
 (HPO:0000316) Hypertelorism rare [HPO:skoehler] 644 / 7739
16
 (HPO:0000347) Micrognathia rare [HPO:skoehler] 426 / 7739
17
 (HPO:0009117) Aplasia/Hypoplasia of the maxilla 18 / 7739
18
 (HPO:0000327) Hypoplasia of the maxilla 129 / 7739
19
 (HPO:0001263) Global developmental delay rare [HPO:skoehler] 853 / 7739
20
 (HPO:0001254) Lethargy 104 / 7739
21
 (HPO:0002533) Abnormal posturing 6 / 7739
22
 (HPO:0006610) Wide intermamillary distance rare [HPO:skoehler] 46 / 7739
23
 (HPO:0002020) Gastroesophageal reflux rare [HPO:skoehler] 101 / 7739
24
 (HPO:0011968) Feeding difficulties 28572511 IBIS 240 / 7739
25
 (HPO:0000023) Inguinal hernia 181 / 7739
26
 (HPO:0001510) Growth delay 295 / 7739
27
 (HPO:0005113) Dilatation of the aortic arch 12 / 7739
28
 (HPO:0002092) Pulmonary hypertension rare [HPO:skoehler] 109 / 7739
29
 (HPO:0001671) Abnormality of the cardiac septa 55 / 7739
30
 (HPO:0001631) Atria septal defect rare [HPO:skoehler] 274 / 7739
31
 (HPO:0001680) Coarctation of aorta rare [HPO:skoehler] 57 / 7739
32
 (HPO:0001873) Thrombocytopenia 224 / 7739
33
 (HPO:0001903) Anemia 289 / 7739
34
 (HPO:0001875) Neutropenia 83 / 7739
35
 (HPO:0003145) Decreased adenosylcobalamin 10 / 7739
36
 (HPO:0002912) Methylmalonic acidemia 14 / 7739
37
 (HPO:0003223) Decreased methylcobalamin rare [HPO:skoehler] 11 / 7739
38
 (HPO:0002160) Hyperhomocystinemia 10 / 7739
39
 (HPO:0003524) Decreased methionine synthase activity rare [HPO:skoehler] 9 / 7739
40
 (HPO:0002789) Tachypnea 48 / 7739
41
 (HPO:0010547) Muscle flaccidity 466 / 7739
42
 (HPO:0001324) Muscle weakness 859 / 7739
43
 (HPO:0008947) Infantile muscular hypotonia 28572511 IBIS 482 / 7739
44
 (HPO:0001252) Muscular hypotonia 28572511 IBIS 990 / 7739
45
 (HPO:0002059) Cerebral atrophy rare [HPO:skoehler] 171 / 7739
46
 (HPO:0003577) Congenital onset 133 / 7739
47
 (OMIM) Breathing difficulties in the neonatal period 1 / 7739
48
 (OMIM) Enlarged right ventricle (1 patient) 1 / 7739
49
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
50
 (OMIM) Decreased activity of methylmalonyl-CoA mutase (MUT, 609058) 2 / 7739
51
 (OMIM) Small left ventricle (1 patient) 1 / 7739
52
 (OMIM) Increased free cyanocobalamin in fibroblasts 2 / 7739
53
 (HPO:0002120) Cerebral cortical atrophy 187 / 7739

Associated genes:

ABCD4

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous metabolic disorder of cobalamin (cbl; vitamin B12) metabolism, which is essential for hematologic and neurologic function. Biochemically, the defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and ...
Clinical Description OMIM Coelho et al. (2012) reported 2 unrelated patients with methylmalonic aciduria and homocystinuria. Both patients showed abnormalities soon after birth. One patient, of North American origin, had respiratory distress, hypotonia, lethargy, poor feeding, periodic breathing, and episodes of ...
Molecular genetics OMIM In 2 unrelated children with methylmalonic aciduria and homocystinuria type cblJ, Coelho et al. (2012) identified 4 different mutations in the ABCD4 gene (603214.0001-603214.0004) in compound heterozygous state. The mutations, which were found using microcell-mediated chromosome transfer and ...