HMAHCHD
MCID: HYP814
MIFTS: 34

Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency (HMAHCHD)

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

Aliases & Classifications for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

MalaCards integrated aliases for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:

Name: Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency 57 72 29 6 39
Hypermethioninemia with Deficiency of S-Adenosylhomocysteine Hydrolase 57 12 20 13
Psychomotor Retardation Due to S-Adenosylhomocysteine Hydrolase Deficiency 12 20
Hypermethioninemia Due to S-Adenosylhomocysteine Hydrolase Deficiency 12 20
Psychomotor Delay Due to S-Adenosylhomocysteine Hydrolase Deficiency 20
S-Adenosylhomocysteine Hydrolase Deficiency 58
Hmahchd 72

Characteristics:

Orphanet epidemiological data:

58
s-adenosylhomocysteine hydrolase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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


HPO:

31
hypermethioninemia with s-adenosylhomocysteine hydrolase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111039
OMIM® 57 613752
MeSH 44 D000592
ICD10 32 E72.1
ICD10 via Orphanet 33 E72.1
UMLS via Orphanet 71 C3151058
Orphanet 58 ORPHA88618
MedGen 41 C3151058

Summaries for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

GARD : 20 Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency (SAHH deficiency) is a muscle disease associated with high blood levels of methionine and creatine kinase (CK). The main symptoms are psychomotor delay, behavioral disorders, severe myopathy, and delayed myelination from birth. Myelin is the layer covering the axons of nerves and plays an important role in nerve impulse conduction. SAHH deficiency is caused by mutations in the AHCY gene. Inheritance is autosomal recessive. A methionine-restricted diet, together with creatine supplements, may partly improve the delayed myelination and psychomotor development. The outcome depends upon the severity of the disease.

MalaCards based summary : Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency, also known as hypermethioninemia with deficiency of s-adenosylhomocysteine hydrolase, is related to hypermethioninemia and myopathy. An important gene associated with Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency is AHCY (Adenosylhomocysteinase). Affiliated tissues include liver, pons and cortex, and related phenotypes are failure to thrive and global developmental delay

Disease Ontology : 12 A hypermethioninemia characterized by autosomal recessive inheritance of psychomotor delay, severe myopathy, hypermethioninaemia and elevated serum creatine kinase levels that has material basis in compound heterozygous mutation in the AHCY gene on chromosome 20q11.

UniProtKB/Swiss-Prot : 72 Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency: A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.

More information from OMIM: 613752

Related Diseases for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

Diseases related to Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 hypermethioninemia 11.5
2 myopathy 10.5
3 hypotonia 10.5
4 hepatocellular carcinoma 10.2
5 factor vii deficiency 10.2
6 phosphoribosylpyrophosphate synthetase superactivity 10.2
7 purine nucleoside phosphorylase deficiency 10.2
8 autosomal recessive disease 10.2
9 microcephaly 10.2
10 respiratory failure 10.2
11 liver disease 10.2
12 eye disease 10.2
13 retinal disease 10.2
14 retinal degeneration 10.2
15 fundus dystrophy 10.2
16 inherited retinal disorder 10.2
17 neurometabolic disease 10.2

Graphical network of the top 20 diseases related to Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:



Diseases related to Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency

Symptoms & Phenotypes for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

Human phenotypes related to Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:

58 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 Frequent (79-30%) HP:0001508
2 global developmental delay 58 31 Frequent (79-30%) HP:0001263
3 abnormality of the dentition 58 31 Occasional (29-5%) HP:0000164
4 abnormal facial shape 58 31 Frequent (79-30%) HP:0001999
5 cardiomyopathy 58 31 Occasional (29-5%) HP:0001638
6 hypermethioninemia 58 31 Occasional (29-5%) HP:0003235
7 intellectual disability 31 HP:0001249
8 muscle weakness 58 Occasional (29-5%)
9 developmental regression 58 Frequent (79-30%)
10 behavioral abnormality 58 Frequent (79-30%)
11 pes planus 58 Occasional (29-5%)
12 microcephaly 58 Occasional (29-5%)
13 strabismus 58 Frequent (79-30%)
14 hydrops fetalis 58 Frequent (79-30%)
15 growth delay 58 Frequent (79-30%)
16 elevated hepatic transaminase 58 Very frequent (99-80%)
17 elevated serum creatine kinase 58 Frequent (79-30%)
18 motor delay 31 HP:0001270
19 ventriculomegaly 58 Occasional (29-5%)
20 abnormality of coagulation 58 Frequent (79-30%)
21 cerebellar hypoplasia 58 Frequent (79-30%)
22 abnormality of the liver 58 Frequent (79-30%)
23 hypoalbuminemia 58 Very frequent (99-80%)
24 prolonged prothrombin time 58 Frequent (79-30%)
25 respiratory failure 58 Occasional (29-5%)
26 hypoplasia of the corpus callosum 58 Frequent (79-30%)
27 poor head control 58 Frequent (79-30%)
28 muscular dystrophy 58 Frequent (79-30%)
29 short attention span 58 Frequent (79-30%)
30 abnormality of hair texture 58 Occasional (29-5%)
31 hypoplasia of the pons 58 Frequent (79-30%)
32 esotropia 58 Frequent (79-30%)
33 widened subarachnoid space 58 Occasional (29-5%)
34 hepatocellular carcinoma 58 Occasional (29-5%)
35 infantile muscular hypotonia 58 Frequent (79-30%)
36 sensorimotor neuropathy 58 Occasional (29-5%)
37 cns hypomyelination 58 Frequent (79-30%)
38 delayed myelination 58 Frequent (79-30%)
39 hypofibrinogenemia 58 Frequent (79-30%)
40 hyperintensity of cerebral white matter on mri 58 Frequent (79-30%)
41 hyperhomocystinemia 58 Very frequent (99-80%)
42 abnormality of methionine metabolism 58 Very frequent (99-80%)
43 abnormality of homocysteine metabolism 58 Very frequent (99-80%)
44 reduced antithrombin iii activity 58 Frequent (79-30%)
45 reduced factor vii activity 58 Frequent (79-30%)
46 elevated coagulation factor v activity 58 Frequent (79-30%)
47 reduced prothrombin activity 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth:
failure to thrive

Facies:
facial dysmorphism

Neuro:
mental and motor retardation

Cardiac:
myocardiopathy

Lab:
hypermethioninemia
placental s-adenosylhomocysteine hydrolase deficiency

Teeth:
abnormal teeth

Hair:
abnormal hair

Clinical features from OMIM®:

613752 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

Search Clinical Trials , NIH Clinical Center for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency

Genetic Tests for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

Genetic tests related to Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:

# Genetic test Affiliating Genes
1 Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency 29 AHCY

Anatomical Context for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

MalaCards organs/tissues related to Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:

40
Liver, Pons, Cortex

Publications for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

Articles related to Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:

(show all 19)
# Title Authors PMID Year
1
S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. 57 6 61
15024124 2004
2
Familial hypermethioninemia partially responsive to dietary restriction. 61 57
2380820 1990
3
Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. 20
27671891 2017
4
CRB1-related retinopathy overlapping the ocular phenotype of S-adenosylhomocysteine hydrolase deficiency. 61
32689861 2020
5
A Turkish patient with novel AHCY variants and presumed diagnosis of S-adenosylhomocysteine hydrolase deficiency. 61
31957987 2020
6
Disruption of Brain Redox Homeostasis, Microglia Activation and Neuronal Damage Induced by Intracerebroventricular Administration of S-Adenosylmethionine to Developing Rats. 61
30058022 2019
7
S-Adenosylmethionine Promotes Oxidative Stress and Decreases Na+, K+-ATPase Activity in Cerebral Cortex Supernatants of Adolescent Rats: Implications for the Pathogenesis of S-Adenosylhomocysteine Hydrolase Deficiency. 61
29101646 2018
8
Adult-onset liver disease and hepatocellular carcinoma in S-adenosylhomocysteine hydrolase deficiency. 61
26527160 2015
9
Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency. 61
26095522 2015
10
Clinical picture of S-adenosylhomocysteine hydrolase deficiency resembles phosphomannomutase 2 deficiency. 61
22959829 2012
11
Plasma biomarker identification in S-adenosylhomocysteine hydrolase deficiency. 61
21732553 2011
12
S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes. 61
20852937 2010
13
Inherited disorders in the conversion of methionine to homocysteine. 61
19585268 2009
14
S-Adenosylhomocysteine hydrolase (AdoHcyase) deficiency: enzymatic capabilities of human AdoHcyase are highly effected by changes to codon 89 and its surrounding residues. 61
18211827 2008
15
A single mutation at Tyr143 of human S-adenosylhomocysteine hydrolase renders the enzyme thermosensitive and affects the oxidation state of bound cofactor nicotinamide-adenine dinucleotide. 61
16872278 2006
16
S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man. 61
16736098 2006
17
S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy. 61
16435181 2005
18
S-Adenosylhomocysteine hydrolase deficiency in cysteine auxotrophs of Tetrahymena thermophila. 61
3989751 1985
19
Proposed explanation for S-adenosylhomocysteine hydrolase deficiency in purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase-deficient patients. 61
6782120 1981

Variations for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

ClinVar genetic disease variations for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:

6 (show top 50) (show all 59)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AHCY NM_000687.4(AHCY):c.336G>A (p.Trp112Ter) SNV Pathogenic 12952 rs121918607 GRCh37: 20:32880273-32880273
GRCh38: 20:34292467-34292467
2 AHCY NM_000687.4(AHCY):c.428A>G (p.Tyr143Cys) SNV Pathogenic 12953 rs121918608 GRCh37: 20:32880181-32880181
GRCh38: 20:34292375-34292375
3 AHCY NM_000687.4(AHCY):c.853C>T (p.Arg285Trp) SNV Conflicting interpretations of pathogenicity 715465 rs116846245 GRCh37: 20:32878358-32878358
GRCh38: 20:34290552-34290552
4 AHCY NM_000687.4(AHCY):c.-34C>T SNV Conflicting interpretations of pathogenicity 218468 rs57344541 GRCh37: 20:32891110-32891110
GRCh38: 20:34303304-34303304
5 AHCY NM_000687.4(AHCY):c.219+7C>G SNV Conflicting interpretations of pathogenicity 338279 rs200332864 GRCh37: 20:32883194-32883194
GRCh38: 20:34295388-34295388
6 AHCY NM_000687.4(AHCY):c.882C>G (p.Ala294=) SNV Conflicting interpretations of pathogenicity 741280 rs376464023 GRCh37: 20:32878228-32878228
GRCh38: 20:34290422-34290422
7 AHCY NM_000687.4(AHCY):c.390C>T (p.Asp130=) SNV Conflicting interpretations of pathogenicity 788172 rs143931269 GRCh37: 20:32880219-32880219
GRCh38: 20:34292413-34292413
8 AHCY NM_000687.4(AHCY):c.1008C>T (p.Ile336=) SNV Conflicting interpretations of pathogenicity 788175 rs139344907 GRCh37: 20:32873405-32873405
GRCh38: 20:34285599-34285599
9 AHCY NM_000687.4(AHCY):c.1000C>T (p.Arg334Cys) SNV Uncertain significance 653403 rs150066229 GRCh37: 20:32873413-32873413
GRCh38: 20:34285607-34285607
10 AHCY NM_000687.4(AHCY):c.855-8C>T SNV Uncertain significance 338272 rs370059571 GRCh37: 20:32878263-32878263
GRCh38: 20:34290457-34290457
11 AHCY NM_000687.4(AHCY):c.97A>G (p.Met33Val) SNV Uncertain significance 471684 rs1555835400 GRCh37: 20:32883323-32883323
GRCh38: 20:34295517-34295517
12 AHCY NM_000687.4(AHCY):c.468G>C (p.Glu156Asp) SNV Uncertain significance 566004 rs1568799740 GRCh37: 20:32879315-32879315
GRCh38: 20:34291509-34291509
13 AHCY NM_000687.4(AHCY):c.936C>T (p.Asn312=) SNV Uncertain significance 895251 GRCh37: 20:32878174-32878174
GRCh38: 20:34290368-34290368
14 AHCY NM_000687.4(AHCY):c.241A>G (p.Ile81Val) SNV Uncertain significance 896687 GRCh37: 20:32881941-32881941
GRCh38: 20:34294135-34294135
15 AHCY NM_000687.4(AHCY):c.-40C>T SNV Uncertain significance 897140 GRCh37: 20:32891116-32891116
GRCh38: 20:34303310-34303310
16 AHCY NM_000687.4(AHCY):c.*583G>C SNV Uncertain significance 898235 GRCh37: 20:32868257-32868257
GRCh38: 20:34280451-34280451
17 AHCY NM_000687.4(AHCY):c.*427T>C SNV Uncertain significance 898236 GRCh37: 20:32868413-32868413
GRCh38: 20:34280607-34280607
18 AHCY NM_000687.4(AHCY):c.*417A>T SNV Uncertain significance 899347 GRCh37: 20:32868423-32868423
GRCh38: 20:34280617-34280617
19 AHCY NM_000687.4(AHCY):c.*181C>T SNV Uncertain significance 899348 GRCh37: 20:32868659-32868659
GRCh38: 20:34280853-34280853
20 AHCY NM_000687.4(AHCY):c.*112G>A SNV Uncertain significance 899349 GRCh37: 20:32868728-32868728
GRCh38: 20:34280922-34280922
21 AHCY NM_000687.4(AHCY):c.1167+15C>A SNV Uncertain significance 899350 GRCh37: 20:32873231-32873231
GRCh38: 20:34285425-34285425
22 AHCY NM_000687.4(AHCY):c.1019C>G (p.Ala340Gly) SNV Uncertain significance 899351 GRCh37: 20:32873394-32873394
GRCh38: 20:34285588-34285588
23 AHCY NM_000687.4(AHCY):c.-63A>G SNV Uncertain significance 338284 rs58942263 GRCh37: 20:32891139-32891139
GRCh38: 20:34303333-34303333
24 AHCY NM_000687.4(AHCY):c.766+2T>G SNV Uncertain significance 631871 rs1348839036 GRCh37: 20:32878535-32878535
GRCh38: 20:34290729-34290729
25 AHCY NC_000020.11:g.(?_34281014)_(34325729_?)dup Duplication Uncertain significance 832601 GRCh37: 20:32868820-32913535
GRCh38:
26 AHCY NM_000687.4(AHCY):c.985C>T (p.Arg329Trp) SNV Uncertain significance 846757 GRCh37: 20:32873428-32873428
GRCh38: 20:34285622-34285622
27 AHCY NM_000687.4(AHCY):c.979C>T (p.Arg327Trp) SNV Uncertain significance 853673 GRCh37: 20:32873434-32873434
GRCh38: 20:34285628-34285628
28 AHCY NM_000687.4(AHCY):c.559-13C>G SNV Uncertain significance 338276 rs763399683 GRCh37: 20:32878757-32878757
GRCh38: 20:34290951-34290951
29 AHCY NM_000687.4(AHCY):c.*678C>T SNV Uncertain significance 338265 rs371150068 GRCh37: 20:32868162-32868162
GRCh38: 20:34280356-34280356
30 AHCY NM_000687.4(AHCY):c.1188A>T (p.Glu396Asp) SNV Uncertain significance 338268 rs886056635 GRCh37: 20:32868951-32868951
GRCh38: 20:34281145-34281145
31 AHCY NM_000687.4(AHCY):c.918C>T (p.Ile306=) SNV Uncertain significance 338271 rs146829385 GRCh37: 20:32878192-32878192
GRCh38: 20:34290386-34290386
32 AHCY NM_000687.4(AHCY):c.61G>A (p.Ala21Thr) SNV Uncertain significance 338280 rs754753419 GRCh37: 20:32883359-32883359
GRCh38: 20:34295553-34295553
33 AHCY NM_000687.4(AHCY):c.445+11C>T SNV Uncertain significance 338277 rs375253690 GRCh37: 20:32880153-32880153
GRCh38: 20:34292347-34292347
34 AHCY NM_000687.4(AHCY):c.-50A>C SNV Uncertain significance 338283 rs199791897 GRCh37: 20:32891126-32891126
GRCh38: 20:34303320-34303320
35 AHCY NM_000687.4(AHCY):c.*621T>C SNV Uncertain significance 338266 rs886056634 GRCh37: 20:32868219-32868219
GRCh38: 20:34280413-34280413
36 AHCY NM_000687.4(AHCY):c.29-4G>A SNV Uncertain significance 338281 rs774846394 GRCh37: 20:32883395-32883395
GRCh38: 20:34295589-34295589
37 AHCY NM_000687.4(AHCY):c.219+8C>T SNV Uncertain significance 338278 rs768480898 GRCh37: 20:32883193-32883193
GRCh38: 20:34295387-34295387
38 AHCY NM_000687.4(AHCY):c.578A>G (p.Tyr193Cys) SNV Uncertain significance 338275 rs772905203 GRCh37: 20:32878725-32878725
GRCh38: 20:34290919-34290919
39 AHCY NM_000687.4(AHCY):c.110A>T (p.Glu37Val) SNV Uncertain significance 218522 rs746513037 GRCh37: 20:32883310-32883310
GRCh38: 20:34295504-34295504
40 AHCY NM_000687.4(AHCY):c.257A>G (p.Asp86Gly) SNV Uncertain significance 631872 rs773162208 GRCh37: 20:32881925-32881925
GRCh38: 20:34294119-34294119
41 AHCY NM_000687.4(AHCY):c.104T>C (p.Met35Thr) SNV Uncertain significance 936017 GRCh37: 20:32883316-32883316
GRCh38: 20:34295510-34295510
42 AHCY NM_000687.4(AHCY):c.698G>A (p.Arg233Gln) SNV Uncertain significance 938535 GRCh37: 20:32878605-32878605
GRCh38: 20:34290799-34290799
43 AHCY NM_000687.4(AHCY):c.685G>A (p.Ala229Thr) SNV Uncertain significance 957545 GRCh37: 20:32878618-32878618
GRCh38: 20:34290812-34290812
44 AHCY NM_000687.4(AHCY):c.1142T>C (p.Val381Ala) SNV Uncertain significance 862308 GRCh37: 20:32873271-32873271
GRCh38: 20:34285465-34285465
45 AHCY NC_000020.10:g.(?_32868820)_(32913535_?)dup Duplication Uncertain significance 1022496 GRCh37: 20:32868820-32913535
GRCh38:
46 AHCY NM_000687.4(AHCY):c.1228A>T (p.Thr410Ser) SNV Uncertain significance 1037891 GRCh37: 20:32868911-32868911
GRCh38: 20:34281105-34281105
47 AHCY NM_000687.4(AHCY):c.1001G>A (p.Arg334His) SNV Uncertain significance 1045453 GRCh37: 20:32873412-32873412
GRCh38: 20:34285606-34285606
48 AHCY NM_000687.4(AHCY):c.942C>T (p.Asn314=) SNV Likely benign 734541 rs767550579 GRCh37: 20:32878168-32878168
GRCh38: 20:34290362-34290362
49 AHCY NM_000687.4(AHCY):c.367G>A (p.Gly123Arg) SNV Likely benign 539061 rs41301825 GRCh37: 20:32880242-32880242
GRCh38: 20:34292436-34292436
50 AHCY NM_000687.4(AHCY):c.767-8_767-7del Microsatellite Likely benign 715349 rs61664915 GRCh37: 20:32878451-32878452
GRCh38: 20:34290645-34290646

UniProtKB/Swiss-Prot genetic disease variations for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 AHCY p.Arg49Cys VAR_058588 rs369428934
2 AHCY p.Asp86Gly VAR_058589 rs773162208
3 AHCY p.Ala89Val VAR_058590 rs755222515
4 AHCY p.Tyr143Cys VAR_058591 rs121918608

Expression for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

Search GEO for disease gene expression data for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency.

Pathways for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

GO Terms for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

Sources for Hypermethioninemia with S-Adenosylhomocysteine Hydrolase...

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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