MCID: HYP769
MIFTS: 36

Hyperlysinemia, Type I

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Hyperlysinemia, Type I

MalaCards integrated aliases for Hyperlysinemia, Type I:

Name: Hyperlysinemia, Type I 57 73
Hyperlysinemia 57 12 76 53 25 59 37 29 13 6 15 40
Lysine Intolerance 57 53 75 73
Alpha-Aminoadipic Semialdehyde Synthase Deficiency 57 53 75
Lysine Alpha-Ketoglutarate Reductase Deficiency Disease 25 73
Alpha-Aminoadipic Semialdehyde Deficiency Disease 25 73
Lysine:alpha-Ketoglutarate Reductase Deficiency 57 75
Lysine Alpha-Ketoglutarate Reductase Deficiency 53 59
L-Lysine:nad-Oxido-Reductase Deficiency 57 75
Hyperlysinemia Type I 59 75
Saccharopinuria 25 73
Hyperlysinemias 44 73
Saccharopine Dehydrogenase Deficiency Disease 25
L-Lysine Nad-Oxido-Reductase Deficiency 53
Alpha-Aminoadipic Semialdehyde Synthase 13
Saccharopine Dehydrogenase Deficiency 73
Familial Hyperlysinemia 25
Hyperlysinemia, 1 75
Hyplys1 75

Characteristics:

Orphanet epidemiological data:

59
hyperlysinemia
Inheritance: Autosomal recessive; Age of onset: All ages; Age of death: any age;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
highly variable phenotype
may be benign condition
about 50% of mutation carriers are asymptomatic


HPO:

32
hyperlysinemia, type i:
Onset and clinical course phenotypic variability infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


Summaries for Hyperlysinemia, Type I

OMIM : 57 Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant (summary by Tondo et al., 2013; Houten et al., 2013). The AASS gene encodes a bifunctional enzyme: lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase. In hyperlysinemia type I, both enzymatic functions of AASS are defective; in hyperlysinemia type II, also known as saccharopinuria (268700), some of the first enzymatic function is retained (Cox, 1985; Cox et al., 1985). (238700)

MalaCards based summary : Hyperlysinemia, Type I, also known as hyperlysinemia, is related to methylmalonic aciduria, cblb type and saccharopinuria, and has symptoms including seizures An important gene associated with Hyperlysinemia, Type I is AASS (Aminoadipate-Semialdehyde Synthase), and among its related pathways/superpathways are Lysine degradation and Amino Acid metabolism. Related phenotypes are abnormality of the genitourinary system and short attention span

UniProtKB/Swiss-Prot : 75 Hyperlysinemia, 1: An autosomal recessive metabolic condition with variable clinical features. Some patients present with non-specific seizures, hypotonia, or mildly delayed psychomotor development, and increased serum lysine and pipecolic acid on laboratory analysis. However, about half of the probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant.

NIH Rare Diseases : 53 Hyperlysinemia is an inherited condition characterized by elevated blood levels of the amino acid lysine. Hyperlysinemia typically causes no health problems, and most people with elevated lysine levels are unaware that they have this condition. Rarely, people with hyperlysinemia have intellectual disability or behavioral problems. Hyperlysinemia is caused by mutations in the AASS gene. It has an autosomal recessive pattern of inheritance.

Genetics Home Reference : 25 Hyperlysinemia is an inherited condition characterized by elevated blood levels of the amino acid lysine, a building block of most proteins. Hyperlysinemia is caused by the shortage (deficiency) of the enzyme that breaks down lysine. Hyperlysinemia typically causes no health problems, and most people with elevated lysine levels are unaware that they have this condition. Rarely, people with hyperlysinemia have intellectual disability or behavioral problems. It is not clear whether these problems are due to hyperlysinemia or another cause.

Disease Ontology : 12 An amino acid metabolic disorder that involves an abnormal increase of lysine in the blood.

Wikipedia : 76 Hyperlysinemia is an autosomal recessivemetabolic disorder characterized by an abnormal increase of... more...

Related Diseases for Hyperlysinemia, Type I

Diseases in the Hyperlysinemia, Type I family:

Hyperlysinemia Due to Defect in Lysine Transport into Mitochondria

Diseases related to Hyperlysinemia, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 methylmalonic aciduria, cblb type 28.8 OTC PC
2 saccharopinuria 11.8
3 citrullinemia, classic 10.0 AASS OTC
4 spastic paraparesis 9.9
5 spasticity 9.9
6 multiple carboxylase deficiency 9.9 OTC PC
7 reye syndrome 9.8 OTC PC
8 hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 9.8 AASS OTC
9 2,4-dienoyl-coa reductase deficiency 9.6 AASS DECR1 NADK2

Graphical network of the top 20 diseases related to Hyperlysinemia, Type I:



Diseases related to Hyperlysinemia, Type I

Symptoms & Phenotypes for Hyperlysinemia, Type I

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
cognitive impairment
mental retardation, mild
language delay
motor deficits

Laboratory Abnormalities:
increased serum, urinary, and csf lysine
increased plasma and urinary pipecolic acid
decreased plasma and urinary ornithine
increased serum, urinary, and csf saccharopine (in some patients)
lysine-ketoglutarate reductase deficiency
more
Neurologic Behavioral Psychiatric Manifestations:
hyperactivity
poor attention span


Clinical features from OMIM:

238700

Human phenotypes related to Hyperlysinemia, Type I:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 abnormality of the genitourinary system 32 HP:0000119
2 short attention span 32 HP:0000736
3 delayed speech and language development 32 HP:0000750
4 hyperactivity 32 HP:0000752
5 ectopia lentis 32 HP:0001083
6 intellectual disability 32 HP:0001249
7 seizures 32 HP:0001250
8 muscular hypotonia 32 HP:0001252
9 intellectual disability, mild 32 HP:0001256
10 anemia 32 HP:0001903
11 hyperlysinemia 32 HP:0002161
12 cognitive impairment 32 HP:0100543

UMLS symptoms related to Hyperlysinemia, Type I:


seizures

MGI Mouse Phenotypes related to Hyperlysinemia, Type I:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 8.92 DECR1 NADK2 OTC PEX5

Drugs & Therapeutics for Hyperlysinemia, Type I

Search Clinical Trials , NIH Clinical Center for Hyperlysinemia, Type I

Cochrane evidence based reviews: hyperlysinemias

Genetic Tests for Hyperlysinemia, Type I

Genetic tests related to Hyperlysinemia, Type I:

# Genetic test Affiliating Genes
1 Hyperlysinemia 29 AASS

Anatomical Context for Hyperlysinemia, Type I

Publications for Hyperlysinemia, Type I

Articles related to Hyperlysinemia, Type I:

# Title Authors Year
1
Lysine intolerance in methylmalonic acidemia. ( 6770332 )
1980
2
Lysine intolerance in a variant form of citrullinemia. ( 503639 )
1979

Variations for Hyperlysinemia, Type I

ClinVar genetic disease variations for Hyperlysinemia, Type I:

6
(show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 AASS NM_005763.3(AASS): c.1601_1609delGTAAACAAG (p.Cys534_Ala871delinsTer) deletion Pathogenic rs387906333 GRCh37 Chromosome 7, 121738550: 121738558
2 AASS NM_005763.3(AASS): c.1601_1609delGTAAACAAG (p.Cys534_Ala871delinsTer) deletion Pathogenic rs387906333 GRCh38 Chromosome 7, 122098496: 122098504
3 AASS NM_005763.3(AASS): c.2662+1_2662+5delGTAAGinsTT indel Pathogenic rs587777121 GRCh37 Chromosome 7, 121717887: 121717891
4 AASS NM_005763.3(AASS): c.2662+1_2662+5delGTAAGinsTT indel Pathogenic rs587777121 GRCh38 Chromosome 7, 122077833: 122077837
5 AASS NM_005763.3(AASS): c.874A> G (p.Ile292Val) single nucleotide variant Pathogenic rs587777122 GRCh37 Chromosome 7, 121756707: 121756707
6 AASS NM_005763.3(AASS): c.874A> G (p.Ile292Val) single nucleotide variant Pathogenic rs587777122 GRCh38 Chromosome 7, 122116653: 122116653
7 AASS NM_005763.3(AASS): c.976_977delCA (p.Gln326Glufs) deletion Pathogenic rs587777123 GRCh37 Chromosome 7, 121755194: 121755195
8 AASS NM_005763.3(AASS): c.976_977delCA (p.Gln326Glufs) deletion Pathogenic rs587777123 GRCh38 Chromosome 7, 122115140: 122115141
9 AASS NM_005763.3(AASS): c.1925C> G (p.Ser642Ter) single nucleotide variant Pathogenic rs587777124 GRCh37 Chromosome 7, 121731848: 121731848
10 AASS NM_005763.3(AASS): c.1925C> G (p.Ser642Ter) single nucleotide variant Pathogenic rs587777124 GRCh38 Chromosome 7, 122091794: 122091794
11 AASS NM_005763.3(AASS): c.194G> A (p.Arg65Gln) single nucleotide variant Pathogenic rs587777125 GRCh37 Chromosome 7, 121773587: 121773587
12 AASS NM_005763.3(AASS): c.194G> A (p.Arg65Gln) single nucleotide variant Pathogenic rs587777125 GRCh38 Chromosome 7, 122133533: 122133533
13 AASS NM_005763.3(AASS): c.1256T> G (p.Leu419Arg) single nucleotide variant Pathogenic rs587777126 GRCh37 Chromosome 7, 121753194: 121753194
14 AASS NM_005763.3(AASS): c.1256T> G (p.Leu419Arg) single nucleotide variant Pathogenic rs587777126 GRCh38 Chromosome 7, 122113140: 122113140

Expression for Hyperlysinemia, Type I

Search GEO for disease gene expression data for Hyperlysinemia, Type I.

Pathways for Hyperlysinemia, Type I

Pathways related to Hyperlysinemia, Type I according to KEGG:

37
# Name Kegg Source Accession
1 Lysine degradation hsa00310

Pathways related to Hyperlysinemia, Type I according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.91 OTC PC
2 9.97 DECR1 PC

GO Terms for Hyperlysinemia, Type I

Cellular components related to Hyperlysinemia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.43 AASS DECR1 NADK2 OTC PC PEX5
2 mitochondrial matrix GO:0005759 9.02 AASS DECR1 NADK2 OTC PC

Biological processes related to Hyperlysinemia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.13 AASS NADK2 PC
2 fatty acid beta-oxidation GO:0006635 8.62 DECR1 PEX5

Sources for Hyperlysinemia, Type I

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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