HMAKD
MCID: HYP241
MIFTS: 37

Hypermethioninemia Due to Adenosine Kinase Deficiency (HMAKD)

Categories: Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hypermethioninemia Due to Adenosine Kinase Deficiency

MalaCards integrated aliases for Hypermethioninemia Due to Adenosine Kinase Deficiency:

Name: Hypermethioninemia Due to Adenosine Kinase Deficiency 57 12 72 29 13 6 15 39
Hypermethioninemia Encephalopathy Due to Adenosine Kinase Deficiency 12 58
Hypermethioninemia Encephalopathy Due to Adk Deficiency 12 58
Adk Hypermethioninemia 12 58
Mrt8 12 72
Mental Retardation, Autosomal Recessive 8, Formerly; Mrt8, Formerly 57
Mental Retardation, Autosomal Recessive 8, Formerly 57
Mental Retardation, Autosomal Recessive 8 70
Mrt8, Formerly 57
Hmakd 72

Characteristics:

Orphanet epidemiological data:

58
hypermethioninemia encephalopathy due to adenosine kinase deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
progressive disorder
six patients have been reported (as of october 2011)


HPO:

31
hypermethioninemia due to adenosine kinase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Hypermethioninemia Due to Adenosine Kinase Deficiency

OMIM® : 57 Hypermethioninemia due to adenosine kinase deficiency is an autosomal recessive inborn error of metabolism characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy); homocysteine is typically normal (summary by Bjursell et al., 2011). (614300) (Updated 05-Apr-2021)

MalaCards based summary : Hypermethioninemia Due to Adenosine Kinase Deficiency, also known as hypermethioninemia encephalopathy due to adenosine kinase deficiency, is related to hypermethioninemia and meier-gorlin syndrome 2. An important gene associated with Hypermethioninemia Due to Adenosine Kinase Deficiency is ADK (Adenosine Kinase). Affiliated tissues include liver and skeletal muscle, and related phenotypes are sensorineural hearing impairment and atrial septal defect

Disease Ontology : 12 A hypermethioninemia characterized by autosomal recessive inheritance of developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia that has material basis in homozygous mutation in the ADK gene on chromosome 10q22.

UniProtKB/Swiss-Prot : 72 Hypermethioninemia due to adenosine kinase deficiency: A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.

Related Diseases for Hypermethioninemia Due to Adenosine Kinase Deficiency

Graphical network of the top 20 diseases related to Hypermethioninemia Due to Adenosine Kinase Deficiency:



Diseases related to Hypermethioninemia Due to Adenosine Kinase Deficiency

Symptoms & Phenotypes for Hypermethioninemia Due to Adenosine Kinase Deficiency

Human phenotypes related to Hypermethioninemia Due to Adenosine Kinase Deficiency:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
2 atrial septal defect 31 occasional (7.5%) HP:0001631
3 coarctation of aorta 31 occasional (7.5%) HP:0001680
4 pulmonic stenosis 31 occasional (7.5%) HP:0001642
5 macrocephaly 31 HP:0000256
6 failure to thrive 31 HP:0001508
7 frontal bossing 31 HP:0002007
8 global developmental delay 31 HP:0001263
9 hypertelorism 31 HP:0000316
10 delayed speech and language development 31 HP:0000750
11 skeletal muscle atrophy 31 HP:0003202
12 hepatic steatosis 31 HP:0001397
13 elevated hepatic transaminase 31 HP:0002910
14 severe global developmental delay 31 HP:0011344
15 cholestasis 31 HP:0001396
16 hyperbilirubinemia 31 HP:0002904
17 cerebral atrophy 31 HP:0002059
18 generalized hypotonia 31 HP:0001290
19 poor speech 31 HP:0002465
20 decreased liver function 31 HP:0001410
21 narrow foot 31 HP:0001786
22 hypermethioninemia 31 HP:0003235
23 portal fibrosis 31 HP:0006580
24 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Head:
macrocephaly
frontal bossing

Growth Other:
failure to thrive

Abdomen Liver:
cholestasis
steatosis
liver dysfunction, mild
portal fibrosis, mild

Muscle Soft Tissue:
hypotonia
muscle wasting

Skeletal Hands:
slender hands

Cardiovascular Heart:
cardiac defects (in some)
atrial septal defect (2 patients)
pulmonary stenosis (1 patient)

Neurologic Central Nervous System:
seizures
cerebral atrophy
hypotonia
poor speech development
global developmental delay, severe
more
Head And Neck Eyes:
hypertelorism

Laboratory Abnormalities:
hyperbilirubinemia
hypermethioninemia
abnormal liver enzymes
increased serum s-adenosylmethionine
increased serum s-adenosylhomocysteine
more
Skeletal Feet:
slender feet

Head And Neck Ears:
hearing loss, sensorineural (in some)

Cardiovascular Vascular:
coarctation of the aorta (1 patient)

Clinical features from OMIM®:

614300 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hypermethioninemia Due to Adenosine Kinase Deficiency

Search Clinical Trials , NIH Clinical Center for Hypermethioninemia Due to Adenosine Kinase Deficiency

Genetic Tests for Hypermethioninemia Due to Adenosine Kinase Deficiency

Genetic tests related to Hypermethioninemia Due to Adenosine Kinase Deficiency:

# Genetic test Affiliating Genes
1 Hypermethioninemia Due to Adenosine Kinase Deficiency 29 ADK

Anatomical Context for Hypermethioninemia Due to Adenosine Kinase Deficiency

MalaCards organs/tissues related to Hypermethioninemia Due to Adenosine Kinase Deficiency:

40
Liver, Skeletal Muscle

Publications for Hypermethioninemia Due to Adenosine Kinase Deficiency

Articles related to Hypermethioninemia Due to Adenosine Kinase Deficiency:

# Title Authors PMID Year
1
Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. 57 6
21963049 2011
2
Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. 57
17120046 2007
3
Homozygosity mapping in outbred families with mental retardation. 61
21248743 2011

Variations for Hypermethioninemia Due to Adenosine Kinase Deficiency

ClinVar genetic disease variations for Hypermethioninemia Due to Adenosine Kinase Deficiency:

6 (show all 38)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ADK NM_006721.4(ADK):c.953C>A (p.Ala318Glu) SNV Pathogenic 29603 rs397514452 GRCh37: 10:76430016-76430016
GRCh38: 10:74670258-74670258
2 ADK , LOC102723439 NM_006721.4(ADK):c.704A>C (p.Asp235Ala) SNV Pathogenic 29604 rs397514453 GRCh37: 10:76285162-76285162
GRCh38: 10:74525404-74525404
3 ADK NM_006721.4(ADK):c.89G>A (p.Gly30Glu) SNV Pathogenic 29605 rs397514454 GRCh37: 10:75960545-75960545
GRCh38: 10:74200787-74200787
4 ADK NM_006721.4(ADK):c.813dup (p.Asn272fs) Duplication Likely pathogenic 800875 rs1589286482 GRCh37: 10:76360186-76360187
GRCh38: 10:74600428-74600429
5 ADK NM_006721.4(ADK):c.1031C>T (p.Ala344Val) SNV Likely pathogenic 802589 rs1589387419 GRCh37: 10:76468145-76468145
GRCh38: 10:74708387-74708387
6 ADK NM_006721.4(ADK):c.429C>T (p.Cys143=) SNV Uncertain significance 877826 GRCh37: 10:76154054-76154054
GRCh38: 10:74394296-74394296
7 ADK NM_006721.4(ADK):c.494A>C (p.Lys165Thr) SNV Uncertain significance 877827 GRCh37: 10:76158276-76158276
GRCh38: 10:74398518-74398518
8 ADK NM_006721.4(ADK):c.*114T>C SNV Uncertain significance 877986 GRCh37: 10:76468317-76468317
GRCh38: 10:74708559-74708559
9 ADK NM_006721.4(ADK):c.*296G>A SNV Uncertain significance 877987 GRCh37: 10:76468499-76468499
GRCh38: 10:74708741-74708741
10 ADK NM_006721.4(ADK):c.*349T>C SNV Uncertain significance 877988 GRCh37: 10:76468552-76468552
GRCh38: 10:74708794-74708794
11 ADK NM_006721.4(ADK):c.66-24133G>A SNV Uncertain significance 879390 GRCh37: 10:75936389-75936389
GRCh38: 10:74176631-74176631
12 ADK NM_006721.4(ADK):c.*729T>G SNV Uncertain significance 879453 GRCh37: 10:76468932-76468932
GRCh38: 10:74709174-74709174
13 ADK NM_006721.4(ADK):c.66-23967G>T SNV Uncertain significance 879774 GRCh37: 10:75936555-75936555
GRCh38: 10:74176797-74176797
14 ADK NM_006721.4(ADK):c.66-23885T>A SNV Uncertain significance 879775 GRCh37: 10:75936637-75936637
GRCh38: 10:74176879-74176879
15 ADK NM_006721.4(ADK):c.71A>T (p.Asn24Ile) SNV Uncertain significance 915419 GRCh37: 10:75960527-75960527
GRCh38: 10:74200769-74200769
16 ADK NM_006721.4(ADK):c.741T>A (p.Phe247Leu) SNV Uncertain significance 191003 rs786205458 GRCh37: 10:76349054-76349054
GRCh38: 10:74589296-74589296
17 ADK NM_006721.4(ADK):c.66-24083G>C SNV Uncertain significance 300832 rs886047233 GRCh37: 10:75936439-75936439
GRCh38: 10:74176681-74176681
18 ADK NM_006721.4(ADK):c.66-24151A>T SNV Uncertain significance 300830 rs886047232 GRCh37: 10:75936371-75936371
GRCh38: 10:74176613-74176613
19 ADK NM_006721.4(ADK):c.66-24009G>T SNV Uncertain significance 300833 rs886047234 GRCh37: 10:75936513-75936513
GRCh38: 10:74176755-74176755
20 ADK NM_006721.4(ADK):c.220A>G (p.Lys74Glu) SNV Uncertain significance 300836 rs201786575 GRCh37: 10:76074450-76074450
GRCh38: 10:74314692-74314692
21 ADK NM_006721.4(ADK):c.763-9T>C SNV Uncertain significance 300842 rs780824505 GRCh37: 10:76360128-76360128
GRCh38: 10:74600370-74600370
22 ADK NM_006721.4(ADK):c.*337T>G SNV Uncertain significance 300845 rs886047238 GRCh37: 10:76468540-76468540
GRCh38: 10:74708782-74708782
23 ADK NM_006721.4(ADK):c.441C>T (p.Asp147=) SNV Uncertain significance 300838 rs886047236 GRCh37: 10:76154066-76154066
GRCh38: 10:74394308-74394308
24 ADK NM_006721.4(ADK):c.*157G>A SNV Uncertain significance 300844 rs886047237 GRCh37: 10:76468360-76468360
GRCh38: 10:74708602-74708602
25 ADK NM_006721.4(ADK):c.66-23966T>C SNV Uncertain significance 300834 rs886047235 GRCh37: 10:75936556-75936556
GRCh38: 10:74176798-74176798
26 ADK NM_006721.4(ADK):c.259A>G (p.Ile87Val) SNV Uncertain significance 300837 rs201734294 GRCh37: 10:76074489-76074489
GRCh38: 10:74314731-74314731
27 ADK NM_006721.4(ADK):c.66-24106T>C SNV Likely benign 300831 rs192064997 GRCh37: 10:75936416-75936416
GRCh38: 10:74176658-74176658
28 ADK NM_006721.4(ADK):c.*740C>T SNV Likely benign 300848 rs150465356 GRCh37: 10:76468943-76468943
GRCh38: 10:74709185-74709185
29 ADK NM_006721.4(ADK):c.66-24289G>A SNV Likely benign 879389 GRCh37: 10:75936233-75936233
GRCh38: 10:74176475-74176475
30 ADK NM_006721.4(ADK):c.1088G>A (p.Ter363=) SNV Likely benign 300843 rs148819558 GRCh37: 10:76468202-76468202
GRCh38: 10:74708444-74708444
31 ADK NM_006721.4(ADK):c.*375A>G SNV Likely benign 300846 rs185021662 GRCh37: 10:76468578-76468578
GRCh38: 10:74708820-74708820
32 ADK NM_006721.4(ADK):c.727-8del Deletion Benign 802588 rs112610475 GRCh37: 10:76349021-76349021
GRCh38: 10:74589263-74589263
33 ADK NM_006721.4(ADK):c.987T>C (p.Ser329=) SNV Benign 716932 rs116653664 GRCh37: 10:76468101-76468101
GRCh38: 10:74708343-74708343
34 ADK , LOC102723439 NM_006721.4(ADK):c.726+11T>G SNV Benign 300840 rs45529443 GRCh37: 10:76285195-76285195
GRCh38: 10:74525437-74525437
35 ADK NM_006721.4(ADK):c.*648C>T SNV Benign 300847 rs1189553 GRCh37: 10:76468851-76468851
GRCh38: 10:74709093-74709093
36 ADK , LOC102723439 NM_006721.4(ADK):c.705T>C (p.Asp235=) SNV Benign 300839 rs16931480 GRCh37: 10:76285163-76285163
GRCh38: 10:74525405-74525405
37 ADK NM_006721.4(ADK):c.727-11T>C SNV Benign 300841 rs12778270 GRCh37: 10:76349029-76349029
GRCh38: 10:74589271-74589271
38 ADK NM_006721.4(ADK):c.66-23911C>T SNV Benign 300835 rs10824095 GRCh37: 10:75936611-75936611
GRCh38: 10:74176853-74176853

UniProtKB/Swiss-Prot genetic disease variations for Hypermethioninemia Due to Adenosine Kinase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 ADK p.Gly30Glu VAR_066640 rs397514454
2 ADK p.Asp235Ala VAR_066641 rs397514453
3 ADK p.Ala318Glu VAR_066642 rs397514452

Expression for Hypermethioninemia Due to Adenosine Kinase Deficiency

Search GEO for disease gene expression data for Hypermethioninemia Due to Adenosine Kinase Deficiency.

Pathways for Hypermethioninemia Due to Adenosine Kinase Deficiency

GO Terms for Hypermethioninemia Due to Adenosine Kinase Deficiency

Biological processes related to Hypermethioninemia Due to Adenosine Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein glycosylation GO:0006486 9.13 TUSC3 ST6GALNAC1 ST3GAL3
2 sialylation GO:0097503 8.62 ST6GALNAC1 ST3GAL3

Molecular functions related to Hypermethioninemia Due to Adenosine Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sialyltransferase activity GO:0008373 8.62 ST6GALNAC1 ST3GAL3

Sources for Hypermethioninemia Due to Adenosine Kinase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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