ACY1D
MCID: AMN007
MIFTS: 36

Aminoacylase 1 Deficiency (ACY1D)

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

Aliases & Classifications for Aminoacylase 1 Deficiency

MalaCards integrated aliases for Aminoacylase 1 Deficiency:

Name: Aminoacylase 1 Deficiency 58 54 26 38 30 13 6 41 17 74
Acy1d 58 54 26 60 76
Deficiency of the Aminoacylase-1 Enzyme 54 26
Neurological Conditions Associated with Aminoacylase 1 Deficiency 60
Encephalopathy Associated with Aminoacylase 1 Deficiency 76
N-Acyl-L-Amino Acid Amidohydrolase Deficiency 60
Aminoacylase-1 Deficiency 76
Acy1 Deficiency 54
Aminoacylase-1 13

Characteristics:

Orphanet epidemiological data:

60
neurological conditions associated with aminoacylase 1 deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
some patients are asymptomatic and detected only by newborn screening
seizures may occur with illness
patients may show normal development


HPO:

33
aminoacylase 1 deficiency:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Aminoacylase 1 Deficiency

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 137754Disease definitionAminoacylase 1 deficiency (ACY1D) is an inborn error of metabolism marked by a characteristic pattern of urinary N-acetyl amino acid excretion and neurologic symptoms.EpidemiologyPrevalence is unknown but less than 20 cases have been reported in the literature so far.Clinical descriptionMost individuals with ACY1D identified so far are children who underwent selective screening tests for inborn errors of metabolism prompted mainly by delayed psychomotor development or by the occurrence of seizures. However, there is a considerable phenotypic variability between ACY1D individuals.EtiologyACY1D is caused by biallelic mutations in the ACY1 gene (3p21.2). ACY1 catalyzes the formation of free amino acids from N-acetylated precursors. The enzyme is strongly expressed in the human brain and is a potential modifier affecting the severity or manifestation of different neurologic diseases.Diagnostic methodsDiagnosis is made by gas chromatography-mass spectrometry (GC-MS) analysis of urinary organic acids revealing increased levels of N-acetylated amino acids, including methionine, glutamine, alanine, leucine, glycine, valine, and isoleucine derivatives, or by NMR spectroscopy of urine. The diagnosis can be confirmed by identification of mutations in the ACY1 gene and by detection of reduced ACY1 enzyme activity in Epstein-Barr virus (EBV)-transformed lymphoblasts or in fibroblasts.Genetic counselingACY1D is transmitted as an autosomal recessivetrait.Management and treatmentManagement is symptomatic only.PrognosisDue to the small number of individuals known to have ACY1D and due to the young age of the reported patients, the clinical course cannot be fully predicted and the prognosis is unknown. Characterization of additional patients and long-term follow-up are indicated.Visit the Orphanet disease page for more resources.

MalaCards based summary : Aminoacylase 1 Deficiency, also known as acy1d, is related to small cell cancer of the lung and lung cancer, and has symptoms including seizures and muscle weakness. An important gene associated with Aminoacylase 1 Deficiency is ACY1 (Aminoacylase 1), and among its related pathways/superpathways are Arginine biosynthesis and Carbon metabolism. Affiliated tissues include brain and testes, and related phenotypes are muscular hypotonia and generalized muscle weakness

Genetics Home Reference : 26 Aminoacylase 1 deficiency is an inherited disorder that can cause neurological problems; the pattern and severity of signs and symptoms vary widely among affected individuals. Individuals with this condition typically have delayed development of mental and motor skills (psychomotor delay). They can have movement problems, reduced muscle tone (hypotonia), mild intellectual disability, and seizures. However, some people with aminoacylase 1 deficiency have no health problems related to the condition. A key feature common to all people with aminoacylase 1 deficiency is high levels of modified protein building blocks (amino acids), called N-acetylated amino acids, in the urine.

OMIM : 58 Aminoacylase-1 deficiency (ACY1D) is a rare autosomal recessive inborn error of metabolism characterized by increased urinary excretion of specific N-actyl amino acids. Most patients show neurologic abnormalities such as intellectual disability, seizures, hypotonia, and motor delay (summary by Ferri et al., 2014). (609924)

UniProtKB/Swiss-Prot : 76 Aminoacylase-1 deficiency: An enzymatic deficiency resulting in encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids.

Wikipedia : 77 Aminoacylase 1 deficiency is a rare inborn error of metabolism. To date only 21 cases have been... more...

Related Diseases for Aminoacylase 1 Deficiency

Diseases related to Aminoacylase 1 Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 small cell cancer of the lung 10.2
2 lung cancer 10.2
3 dystonia 12 10.1
4 dystonia 10.1
5 hepatitis 10.0
6 hepatitis b 10.0
7 liver cirrhosis 10.0
8 herpes simplex 10.0

Graphical network of the top 20 diseases related to Aminoacylase 1 Deficiency:



Diseases related to Aminoacylase 1 Deficiency

Symptoms & Phenotypes for Aminoacylase 1 Deficiency

Human phenotypes related to Aminoacylase 1 Deficiency:

60 33 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0001252
2 generalized muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0003324
3 encephalopathy 60 33 frequent (33%) Frequent (79-30%) HP:0001298
4 seizures 60 33 occasional (7.5%) Occasional (29-5%) HP:0001250
5 global developmental delay 60 33 occasional (7.5%) Occasional (29-5%) HP:0001263
6 vomiting 60 33 occasional (7.5%) Occasional (29-5%) HP:0002013
7 apnea 60 33 occasional (7.5%) Occasional (29-5%) HP:0002104
8 aplasia/hypoplasia of the corpus callosum 60 33 occasional (7.5%) Occasional (29-5%) HP:0007370
9 syringomyelia 60 33 occasional (7.5%) Occasional (29-5%) HP:0003396
10 aplasia/hypoplasia of the cerebellar vermis 60 33 occasional (7.5%) Occasional (29-5%) HP:0006817
11 hypertelorism 60 33 very rare (1%) Very rare (<4-1%) HP:0000316
12 sensorineural hearing impairment 60 33 very rare (1%) Very rare (<4-1%) HP:0000407
13 wide nose 60 33 very rare (1%) Very rare (<4-1%) HP:0000445
14 muscle weakness 33 HP:0001324
15 wide nasal bridge 33 HP:0000431
16 cerebellar atrophy 33 HP:0001272
17 generalized hypotonia 33 HP:0001290
18 hyperactivity 33 HP:0000752
19 cerebral atrophy 33 HP:0002059
20 delayed cns myelination 33 HP:0002188
21 acute encephalopathy 33 HP:0006846

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
acute encephalopathy
psychomotor retardation, mild to moderate
cerebral atrophy (reported in 1 patient)
cerebellar atrophy (reported in 1 patient)
more
Head And Neck Ears:
sensorineural hearing loss (reported in 1 patient)

Head And Neck Nose:
broad nasal root (reported in 1 patient)

Laboratory Abnormalities:
decreased aminoacylase-1 activity
increased urinary n-acetylated amino acids

Muscle Soft Tissue:
muscle weakness
hypotonia

Head And Neck Eyes:
hypertelorism (reported in 1 patient)

Neurologic Behavioral Psychiatric Manifestations:
hyperactivity (reported in 1 patient)

Clinical features from OMIM:

609924

UMLS symptoms related to Aminoacylase 1 Deficiency:


seizures, muscle weakness

Drugs & Therapeutics for Aminoacylase 1 Deficiency

Search Clinical Trials , NIH Clinical Center for Aminoacylase 1 Deficiency

Genetic Tests for Aminoacylase 1 Deficiency

Genetic tests related to Aminoacylase 1 Deficiency:

# Genetic test Affiliating Genes
1 Aminoacylase 1 Deficiency 30 ACY1

Anatomical Context for Aminoacylase 1 Deficiency

MalaCards organs/tissues related to Aminoacylase 1 Deficiency:

42
Brain, Testes

Publications for Aminoacylase 1 Deficiency

Articles related to Aminoacylase 1 Deficiency:

# Title Authors Year
1
The molecular basis of aminoacylase 1 deficiency. ( 21414403 )
2011
2
Aminoacylase 1 deficiency associated with autistic behavior. ( 20480396 )
2010
3
NMR spectroscopy of aminoacylase 1 deficiency, a novel inborn error of metabolism. ( 17516490 )
2008
4
Neurological findings in aminoacylase 1 deficiency. ( 17562838 )
2007

Variations for Aminoacylase 1 Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Aminoacylase 1 Deficiency:

76
# Symbol AA change Variation ID SNP ID
1 ACY1 p.Arg386Cys VAR_020452 rs2229152
2 ACY1 p.Glu233Asp VAR_026104 rs121912699
3 ACY1 p.Arg353Cys VAR_026105 rs121912698
4 ACY1 p.Arg197Trp VAR_043113 rs121912700
5 ACY1 p.Arg393His VAR_043114 rs121912701
6 ACY1 p.Arg378Gln VAR_065562 rs150480963
7 ACY1 p.Arg378Trp VAR_065563 rs148346337

ClinVar genetic disease variations for Aminoacylase 1 Deficiency:

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 ACY1 NM_000666.2(ACY1): c.1001_1001+5delTGTGAG deletion Pathogenic rs672601350 GRCh38 Chromosome 3, 51988603: 51988608
2 ACY1 NM_000666.2(ACY1): c.1001_1001+5delTGTGAG deletion Pathogenic rs672601350 GRCh37 Chromosome 3, 52022619: 52022624
3 ACY1 NM_000666.2(ACY1): c.1104_1105dupAC (p.Pro369Hisfs) duplication Pathogenic rs387906579 GRCh37 Chromosome 3, 52022968: 52022969
4 ACY1 NM_000666.2(ACY1): c.1104_1105dupAC (p.Pro369Hisfs) duplication Pathogenic rs387906579 GRCh38 Chromosome 3, 51988952: 51988953
5 ACY1 NM_001198896.1(ACY1): c.841C> T (p.Arg281Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs121912698 GRCh37 Chromosome 3, 52022837: 52022837
6 ACY1 NM_001198896.1(ACY1): c.841C> T (p.Arg281Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs121912698 GRCh38 Chromosome 3, 51988821: 51988821
7 ACY1 NM_000666.2(ACY1): c.699A> C (p.Glu233Asp) single nucleotide variant Pathogenic rs121912699 GRCh37 Chromosome 3, 52021204: 52021204
8 ACY1 NM_000666.2(ACY1): c.699A> C (p.Glu233Asp) single nucleotide variant Pathogenic rs121912699 GRCh38 Chromosome 3, 51987188: 51987188
9 ACY1 NM_000666.2(ACY1): c.360-1G> A single nucleotide variant Pathogenic rs672601330 GRCh37 Chromosome 3, 52020270: 52020270
10 ACY1 NM_000666.2(ACY1): c.360-1G> A single nucleotide variant Pathogenic rs672601330 GRCh38 Chromosome 3, 51986254: 51986254
11 ACY1 NM_000666.2(ACY1): c.589C> T (p.Arg197Trp) single nucleotide variant Pathogenic rs121912700 GRCh37 Chromosome 3, 52021009: 52021009
12 ACY1 NM_000666.2(ACY1): c.589C> T (p.Arg197Trp) single nucleotide variant Pathogenic rs121912700 GRCh38 Chromosome 3, 51986993: 51986993
13 ACY1 NM_000666.2(ACY1): c.1178G> A (p.Arg393His) single nucleotide variant Conflicting interpretations of pathogenicity rs121912701 GRCh37 Chromosome 3, 52023042: 52023042
14 ACY1 NM_000666.2(ACY1): c.1178G> A (p.Arg393His) single nucleotide variant Conflicting interpretations of pathogenicity rs121912701 GRCh38 Chromosome 3, 51989026: 51989026
15 ACY1 NM_000666.2(ACY1): c.1001T> C (p.Met334Thr) single nucleotide variant Uncertain significance rs750876815 GRCh37 Chromosome 3, 52022619: 52022619
16 ACY1 NM_000666.2(ACY1): c.1001T> C (p.Met334Thr) single nucleotide variant Uncertain significance rs750876815 GRCh38 Chromosome 3, 51988603: 51988603

Expression for Aminoacylase 1 Deficiency

Search GEO for disease gene expression data for Aminoacylase 1 Deficiency.

Pathways for Aminoacylase 1 Deficiency

Pathways related to Aminoacylase 1 Deficiency according to KEGG:

38
# Name Kegg Source Accession
1 Arginine biosynthesis hsa00220

Pathways related to Aminoacylase 1 Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.28 ABHD14A-ACY1 ACY1
2
Show member pathways
10.04 ABHD14A-ACY1 ACY1

GO Terms for Aminoacylase 1 Deficiency

Biological processes related to Aminoacylase 1 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proteolysis GO:0006508 8.96 ABHD14A-ACY1 ACY1
2 cellular amino acid metabolic process GO:0006520 8.62 ABHD14A-ACY1 ACY1

Molecular functions related to Aminoacylase 1 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 8.96 ABHD14A-ACY1 ACY1
2 metallopeptidase activity GO:0008237 8.62 ABHD14A-ACY1 ACY1

Sources for Aminoacylase 1 Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
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45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
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52 NDF-RT
55 NINDS
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58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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