ACY1D
MCID: AMN007
MIFTS: 33

Aminoacylase 1 Deficiency (ACY1D)

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

Aliases & Classifications for Aminoacylase 1 Deficiency

MalaCards integrated aliases for Aminoacylase 1 Deficiency:

Name: Aminoacylase 1 Deficiency 57 20 43 36 29 13 6 39 17 70
Acy1d 57 20 43 58 72
Deficiency of the Aminoacylase-1 Enzyme 20 43
Neurological Conditions Associated with Aminoacylase 1 Deficiency 58
Encephalopathy Associated with Aminoacylase 1 Deficiency 72
N-Acyl-L-Amino Acid Amidohydrolase Deficiency 58
Aminoacylase-1 Deficiency 72
Acy1 Deficiency 20

Characteristics:

Orphanet epidemiological data:

58
neurological conditions associated with aminoacylase 1 deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 20-May-2021)
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:

31
aminoacylase 1 deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Aminoacylase 1 Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 137754 Definition An inborn error of metabolism marked by a characteristic pattern of urinary N-acetyl amino acid excretion and neurologic symptoms. Epidemiology Prevalence is unknown but less than 20 cases have been reported in the literature so far. Clinical description Most 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. Etiology ACY1D 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 methods Diagnosis 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 counseling ACY1D is transmitted as an autosomal recessive trait. Management and treatment Management is symptomatic only. Prognosis Due 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.

MalaCards based summary : Aminoacylase 1 Deficiency, also known as acy1d, is related to inherited metabolic disorder and febrile seizures, 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. Related phenotypes are encephalopathy and generalized muscle weakness

MedlinePlus Genetics : 43 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® : 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) (Updated 20-May-2021)

KEGG : 36 Aminoacylase 1 deficiency is an autosomal recessive disease characterized by accumulation of N-acetyl amino acids in the urine. In affected individuals neurological findings such as febrile seizures, delay of psychomotor development and moderate mental retardation have been reported.

UniProtKB/Swiss-Prot : 72 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 : 73 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 inherited metabolic disorder 10.0
2 febrile seizures 10.0
3 organic acidemia 10.0
4 dystonia 10.0

Symptoms & Phenotypes for Aminoacylase 1 Deficiency

Human phenotypes related to Aminoacylase 1 Deficiency:

58 31 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 encephalopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001298
2 generalized muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003324
3 hypotonia 31 frequent (33%) HP:0001252
4 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
5 vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002013
6 apnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002104
7 aplasia/hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0007370
8 syringomyelia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003396
9 aplasia/hypoplasia of the cerebellar vermis 58 31 occasional (7.5%) Occasional (29-5%) HP:0006817
10 seizure 31 occasional (7.5%) HP:0001250
11 hypertelorism 58 31 very rare (1%) Very rare (<4-1%) HP:0000316
12 sensorineural hearing impairment 58 31 very rare (1%) Very rare (<4-1%) HP:0000407
13 wide nose 58 31 very rare (1%) Very rare (<4-1%) HP:0000445
14 seizures 58 Occasional (29-5%)
15 muscular hypotonia 58 Frequent (79-30%)
16 muscle weakness 31 HP:0001324
17 wide nasal bridge 31 HP:0000431
18 cerebellar atrophy 31 HP:0001272
19 psychomotor retardation 31 HP:0025356
20 cerebral atrophy 31 HP:0002059
21 hyperactivity 31 HP:0000752
22 generalized hypotonia 31 HP:0001290
23 acute encephalopathy 31 HP:0006846
24 delayed cns myelination 31 HP:0002188

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

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

Publications for Aminoacylase 1 Deficiency

Articles related to Aminoacylase 1 Deficiency:

# Title Authors PMID Year
1
Neurological findings in aminoacylase 1 deficiency. 61 57 6
17562838 2007
2
Aminoacylase I deficiency due to ACY1 mRNA exon skipping. 57 6
24117009 2014
3
Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. 57 6
16465618 2006
4
Aminoacylase I deficiency: a novel inborn error of metabolism. 57 6
16274666 2005
5
Four years follow up of ACY1 deficient patient and pedigree study. 61
29653693 2018
6
The molecular basis of aminoacylase 1 deficiency. 61
21414403 2011
7
Aminoacylase 1 deficiency associated with autistic behavior. 61
20480396 2010
8
NMR spectroscopy of aminoacylase 1 deficiency, a novel inborn error of metabolism. 61
17516490 2008

Variations for Aminoacylase 1 Deficiency

ClinVar genetic disease variations for Aminoacylase 1 Deficiency:

6 (show all 18)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.575dup (p.Ser192fs) Duplication Pathogenic 800812 rs770702363 GRCh37: 3:52020668-52020669
GRCh38: 3:51986652-51986653
2 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.699A>C (p.Glu233Asp) SNV Pathogenic 18111 rs121912699 GRCh37: 3:52021204-52021204
GRCh38: 3:51987188-51987188
3 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.360-1G>A SNV Pathogenic 18112 rs672601330 GRCh37: 3:52020270-52020270
GRCh38: 3:51986254-51986254
4 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.589C>T (p.Arg197Trp) SNV Pathogenic 18113 rs121912700 GRCh37: 3:52021009-52021009
GRCh38: 3:51986993-51986993
5 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1178G>A (p.Arg393His) SNV Pathogenic 18114 rs121912701 GRCh37: 3:52023042-52023042
GRCh38: 3:51989026-51989026
6 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1001_1001+5del Deletion Pathogenic 162019 rs672601350 GRCh37: 3:52022619-52022624
GRCh38: 3:51988603-51988608
7 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1102_1103AC[3] (p.Pro369fs) Microsatellite Pathogenic 18109 rs387906579 GRCh37: 3:52022964-52022965
GRCh38: 3:51988948-51988949
8 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1057C>T (p.Arg353Cys) SNV Conflicting interpretations of pathogenicity 18110 rs121912698 GRCh37: 3:52022837-52022837
GRCh38: 3:51988821-51988821
9 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1001T>C (p.Met334Thr) SNV Uncertain significance 547895 rs750876815 GRCh37: 3:52022619-52022619
GRCh38: 3:51988603-51988603
10 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1156C>T (p.Arg386Cys) SNV Uncertain significance 712435 rs2229152 GRCh37: 3:52023020-52023020
GRCh38: 3:51989004-51989004
11 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1100G>A (p.Arg367His) SNV Uncertain significance 709571 rs201647575 GRCh37: 3:52022964-52022964
GRCh38: 3:51988948-51988948
12 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1000A>T (p.Met334Leu) SNV Uncertain significance 973465 GRCh37: 3:52022618-52022618
GRCh38: 3:51988602-51988602
13 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1132C>T (p.Arg378Trp) SNV Uncertain significance 493363 rs148346337 GRCh37: 3:52022996-52022996
GRCh38: 3:51988980-51988980
14 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1201G>T (p.Val401Leu) SNV Uncertain significance 1029929 GRCh37: 3:52023065-52023065
GRCh38: 3:51989049-51989049
15 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.19G>C (p.Glu7Gln) SNV Uncertain significance 1029930 GRCh37: 3:52018099-52018099
GRCh38: 3:51984083-51984083
16 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.437-19G>A SNV Uncertain significance 1029931 GRCh37: 3:52020412-52020412
GRCh38: 3:51986396-51986396
17 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.921+21A>T SNV Uncertain significance 1029932 GRCh37: 3:52021661-52021661
GRCh38: 3:51987645-51987645
18 ABHD14A-ACY1 , ACY1 NM_000666.3(ACY1):c.1177C>T (p.Arg393Cys) SNV Uncertain significance 726734 rs6804746 GRCh37: 3:52023041-52023041
GRCh38: 3:51989025-51989025

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

72
# 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

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:

36
# 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 ACY1 ABHD14A-ACY1
2
Show member pathways
10.05 ACY1 ABHD14A-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 cellular amino acid metabolic process GO:0006520 8.62 ACY1 ABHD14A-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 ACY1 ABHD14A-ACY1
2 aminoacylase activity GO:0004046 8.62 ACY1 ABHD14A-ACY1

Sources for Aminoacylase 1 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....