MCID: AMN007
MIFTS: 35

Aminoacylase 1 Deficiency

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

Aliases & Classifications for Aminoacylase 1 Deficiency

MalaCards integrated aliases for Aminoacylase 1 Deficiency:

Name: Aminoacylase 1 Deficiency 57 53 25 37 29 13 6 40 73
Acy1d 57 53 25 59 75
Deficiency of the Aminoacylase-1 Enzyme 53 25
Neurological Conditions Associated with Aminoacylase 1 Deficiency 59
Encephalopathy Associated with Aminoacylase 1 Deficiency 75
N-Acyl-L-Amino Acid Amidohydrolase Deficiency 59
Aminoacylase-1 Deficiency 75
Acy1 Deficiency 53
Aminoacylase-1 13

Characteristics:

Orphanet epidemiological data:

59
neurological conditions associated with aminoacylase 1 deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

57
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:

32
aminoacylase 1 deficiency:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Aminoacylase 1 Deficiency

NIH Rare Diseases : 53 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 testes and brain, and related phenotypes are hypertelorism and sensorineural hearing impairment

OMIM : 57 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 : 75 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.

Genetics Home Reference : 25 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.

Wikipedia : 76 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 10.0
2 lung cancer 10.0
3 dystonia 10.0
4 hepatitis 9.9
5 hepatitis b 9.9
6 liver cirrhosis 9.9
7 herpes simplex 9.9

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



Diseases related to Aminoacylase 1 Deficiency

Symptoms & Phenotypes for Aminoacylase 1 Deficiency

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Aminoacylase 1 Deficiency:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 sensorineural hearing impairment 32 HP:0000407
3 wide nasal bridge 32 HP:0000431
4 hyperactivity 32 HP:0000752
5 seizures 32 HP:0001250
6 muscular hypotonia 32 HP:0001252
7 global developmental delay 32 HP:0001263
8 cerebellar atrophy 32 HP:0001272
9 generalized hypotonia 32 HP:0001290
10 muscle weakness 32 HP:0001324
11 cerebral atrophy 32 HP:0002059
12 delayed cns myelination 32 HP:0002188
13 acute encephalopathy 32 HP:0006846

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 29 ACY1

Anatomical Context for Aminoacylase 1 Deficiency

MalaCards organs/tissues related to Aminoacylase 1 Deficiency:

41
Testes, Brain

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:

75
# 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
# Gene Variation Type Significance SNP ID Assembly Location
1 ACY1 NM_000666.2(ACY1): c.1104_1105dupAC (p.Pro369Hisfs) duplication Pathogenic rs387906579 GRCh37 Chromosome 3, 52022968: 52022969
2 ACY1 NM_000666.2(ACY1): c.1104_1105dupAC (p.Pro369Hisfs) duplication Pathogenic rs387906579 GRCh38 Chromosome 3, 51988952: 51988953
3 ACY1 NM_000666.2(ACY1): c.699A> C (p.Glu233Asp) single nucleotide variant Pathogenic rs121912699 GRCh37 Chromosome 3, 52021204: 52021204
4 ACY1 NM_000666.2(ACY1): c.699A> C (p.Glu233Asp) single nucleotide variant Pathogenic rs121912699 GRCh38 Chromosome 3, 51987188: 51987188
5 ACY1 NM_000666.2(ACY1): c.360-1G> A single nucleotide variant Pathogenic rs672601330 GRCh37 Chromosome 3, 52020270: 52020270
6 ACY1 NM_000666.2(ACY1): c.360-1G> A single nucleotide variant Pathogenic rs672601330 GRCh38 Chromosome 3, 51986254: 51986254
7 ACY1 NM_000666.2(ACY1): c.589C> T (p.Arg197Trp) single nucleotide variant Pathogenic rs121912700 GRCh37 Chromosome 3, 52021009: 52021009
8 ACY1 NM_000666.2(ACY1): c.589C> T (p.Arg197Trp) single nucleotide variant Pathogenic rs121912700 GRCh38 Chromosome 3, 51986993: 51986993
9 ACY1 NM_000666.2(ACY1): c.1001_1001+5delTGTGAG deletion Pathogenic rs672601350 GRCh37 Chromosome 3, 52022619: 52022624
10 ACY1 NM_000666.2(ACY1): c.1001_1001+5delTGTGAG deletion Pathogenic rs672601350 GRCh38 Chromosome 3, 51988603: 51988608

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:

37
# 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 9.16 ABHD14A-ACY1 ACY1
2 metabolic process GO:0008152 8.96 ABHD14A-ACY1 ACY1
3 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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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