HYPLYS1
MCID: HYP769
MIFTS: 42

Hyperlysinemia, Type I (HYPLYS1)

Categories: Blood diseases, Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Hyperlysinemia, Type I

MalaCards integrated aliases for Hyperlysinemia, Type I:

Name: Hyperlysinemia, Type I 57 70
Hyperlysinemia 57 12 73 20 43 58 36 29 13 6 15 39
Alpha-Aminoadipic Semialdehyde Synthase Deficiency 57 20 72 6
Lysine Intolerance 57 20 72 70
Lysine Alpha-Ketoglutarate Reductase Deficiency Disease 43 70
Alpha-Aminoadipic Semialdehyde Deficiency Disease 43 70
Lysine:alpha-Ketoglutarate Reductase Deficiency 57 72
Lysine Alpha-Ketoglutarate Reductase Deficiency 20 58
L-Lysine:nad-Oxido-Reductase Deficiency 57 72
Hyperlysinemia Type I 58 72
Saccharopinuria 43 70
Hyperlysinemias 44 70
Saccharopine Dehydrogenase Deficiency Disease 43
L-Lysine Nad-Oxido-Reductase Deficiency 20
Saccharopine Dehydrogenase Deficiency 70
Familial Hyperlysinemia 43
Hyperlysinemia, 1 72
Hyplys1 72

Characteristics:

Orphanet epidemiological data:

58
hyperlysinemia
Inheritance: Autosomal recessive; Age of onset: All ages; Age of death: any age;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

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


HPO:

31
hyperlysinemia, type i:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:9274
OMIM® 57 238700
KEGG 36 H00188
MeSH 44 D020167
NCIt 50 C123433
SNOMED-CT 67 58558003
ICD10 32 E72.3
MESH via Orphanet 45 D020167
ICD10 via Orphanet 33 E72.3
UMLS via Orphanet 71 C0268553 C0936256
Orphanet 58 ORPHA2203
UMLS 70 C0268553 C0268556 C0543533 more

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., 1986). (238700) (Updated 20-May-2021)

MalaCards based summary : Hyperlysinemia, Type I, also known as hyperlysinemia, is related to 2,4-dienoyl-coa reductase deficiency 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 is Lysine degradation. Affiliated tissues include cortex, brain and kidney, and related phenotypes are intellectual disability and delayed speech and language development

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

MedlinePlus Genetics : 43 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.

GARD : 20 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.

KEGG : 36 Hyperlysinemia is an autosomal recessive metabolic disorder caused by aminoadipate-semialdehyde synthase deficiency and characterized by an abnormal increase of lysine in the blood.

UniProtKB/Swiss-Prot : 72 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.

Wikipedia : 73 Hyperlysinemia is an autosomal recessive metabolic 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:

(show all 31)
# Related Disease Score Top Affiliating Genes
1 2,4-dienoyl-coa reductase deficiency 32.1 NADK2 DECR1 AASS
2 saccharopinuria 11.6
3 hyperlysinemia due to defect in lysine transport into mitochondria 10.9
4 hyperlysinuria with hyperammonemia 10.9
5 carbonic anhydrase va deficiency, hyperammonemia due to 10.2
6 purine-pyrimidine metabolic disorder 10.1 SUOX PRODH
7 xanthinuria 10.1 SUOX PRODH
8 argininemia 10.0
9 orotic aciduria 10.0
10 multiple acyl-coa dehydrogenase deficiency 10.0 PRODH NADK2 DECR1
11 cystinuria 9.9
12 argininosuccinic aciduria 9.9
13 propionic acidemia 9.9
14 reye syndrome 9.9
15 lactic acidosis 9.9
16 spastic paraparesis 9.9
17 hypertonia 9.9
18 citrullinemia, classic 9.9
19 citrullinemia, type ii, adult-onset 9.9
20 methylmalonic acidemia 9.9
21 isolated methylmalonic acidemia 9.9
22 glutaric acidemia i 9.9 SLC25A18 DHTKD1
23 ectopia lentis 1, isolated, autosomal dominant 9.8 SUOX ADAMTSL4
24 ectopia lentis 2, isolated, autosomal recessive 9.8 SUOX ADAMTSL4
25 glycine encephalopathy 9.8 SUOX PRODH
26 lens subluxation 9.8 SUOX ADAMTSL4
27 hyperprolinemia, type i 9.8 SUOX PRODH NADK2 DECR1
28 sulfite oxidase deficiency, isolated 9.8 SUOX ADAMTSL4
29 hyperprolinemia, type ii 9.7 PRODH NADK2 DECR1 AASDH
30 isolated ectopia lentis 9.7 SUOX ADAMTSL4
31 zellweger syndrome 9.7 SUOX AASS AASDH

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



Diseases related to Hyperlysinemia, Type I

Symptoms & Phenotypes for Hyperlysinemia, Type I

Human phenotypes related to Hyperlysinemia, Type I:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 delayed speech and language development 31 HP:0000750
3 cognitive impairment 31 HP:0100543
4 intellectual disability, mild 31 HP:0001256
5 anemia 31 HP:0001903
6 ectopia lentis 31 HP:0001083
7 abnormality of the genitourinary system 31 HP:0000119
8 hyperactivity 31 HP:0000752
9 short attention span 31 HP:0000736
10 hyperlysinemia 31 HP:0002161
11 seizure 31 HP:0001250
12 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

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

UMLS symptoms related to Hyperlysinemia, Type I:


seizures

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

26 (show all 16)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 9.55 DHTKD1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-121 9.55 ADAMTSL4
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-136 9.55 PRODH
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.55 PRODH
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-152 9.55 ADAMTSL4 DHTKD1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-180 9.55 ADAMTSL4
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-192 9.55 PRODH
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-198 9.55 PRODH
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 9.55 PRODH
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-25 9.55 DHTKD1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-4 9.55 PRODH
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-5 9.55 PRODH
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.55 PRODH
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-6 9.55 ADAMTSL4
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-86 9.55 PRODH
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.55 ADAMTSL4

MGI Mouse Phenotypes related to Hyperlysinemia, Type I:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.23 AASDH ADAMTSL4 DECR1 DHTKD1 NADK2 PRODH

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

MalaCards organs/tissues related to Hyperlysinemia, Type I:

40
Cortex, Brain, Kidney

Publications for Hyperlysinemia, Type I

Articles related to Hyperlysinemia, Type I:

(show top 50) (show all 55)
# Title Authors PMID Year
1
Clinical, biochemical, molecular and therapeutic aspects of 2 new cases of 2-aminoadipic semialdehyde synthase deficiency. 61 6 57
23890588 2013
2
Genetic basis of hyperlysinemia. 57 6 61
23570448 2013
3
Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia. 57 6 61
10775527 2000
4
Multiple enzyme defects in familial hyperlysinemia. 6 57 61
934735 1976
5
Familial hyperlysinemias. Purification and characterization of the bifunctional aminoadipic semialdehyde synthase with lysine-ketoglutarate reductase and saccharopine dehydrogenase activities. 61 57
6434529 1984
6
The prognosis of hyperlysinemia: an interim report. 57 61
6407303 1983
7
Hyperlysinemia with saccharopinuria due to combined lysine-ketoglutarate reductase and saccharopine dehydrogenase deficiencies presenting as cystinuria. 61 57
571908 1979
8
Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology. 57 61
463877 1979
9
Excretion of hypusine by children and by patients with familial hyperlysinemia. 61 57
4753051 1973
10
Ocular manifestations of familial hyperlysinemia. 61 57
5557172 1971
11
Familial hyperlysinemia with lysine-ketoglutarate reductase insufficiency. 57 61
5796356 1969
12
Hyperlysinemia associated with retardation. 61 57
5825685 1965
13
HYPERLYSINEMIA. 61 57
14209691 1964
14
Familial hyperlysinemias--multiple enzyme deficiencies associated with the bifunctional aminoadipic semialdehyde synthase. 57
3939388 1986
15
Saccharopinuria: a new inborn error of lysine metabolism. 57
5690339 1968
16
Lysine intolerance with periodic ammonia intoxication. 57
6015890 1967
17
The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis. 61
30573525 2019
18
Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant. 61
29388319 2018
19
Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. 61
24847004 2014
20
Pipecolic acid induces oxidative stress in vitro in cerebral cortex of young rats and the protective role of lipoic acid. 61
24338030 2014
21
Neurochemical evidence that lysine inhibits synaptic Na+,K+-ATPase activity and provokes oxidative damage in striatum of young rats in vivo. 61
20976553 2011
22
Inhibition of creatine kinase activity by lysine in rat cerebral cortex. 61
19370404 2009
23
Alpha-aminoadipate delta-semialdehyde synthase mRNA knockdown reduces the lysine requirement of a mouse hepatic cell line. 61
18936211 2008
24
Lysine induces lipid and protein damage and decreases reduced glutathione concentrations in brain of young rats. 61
18691648 2008
25
Plasma lysine concentration and availability of 2-ketoglutarate in liver mitochondria. 61
11999975 2002
26
[Saccharopinuria (a variant form of familial hyperlysinemia)]. 61
9590025 1998
27
[Familial hyperlysinemia(alpha-aminoadipic semialdehyde synthase defect)]. 61
9590024 1998
28
L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients. 61
9187477 1997
29
Familial hyperlysinemia in a patient presenting with progressive spastic paraparesis. 61
8797497 1996
30
[Hyperlysinemia and hyperammonemia]. 61
1904697 1991
31
[Inborn errors of lysine metabolism]. 61
1904694 1991
32
2,4-Dienoyl-coenzyme A reductase deficiency: a possible new disorder of fatty acid oxidation. 61
2332510 1990
33
Lysine transport in human kidney. 61
2112825 1990
34
The significance of hyperpipecolatemia in Zellweger syndrome. 61
3087161 1986
35
Biochemical and histologic pathology in an infant with cross-reacting material (negative) pyruvate carboxylase deficiency. 61
3085060 1986
36
The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency. 61
6424438 1984
37
[A patient with persistent hyperlysinemia]. 61
6407142 1983
38
Separation of ornithine and lysine activities of the ornithine-transcarbamylase-catalyzed reaction. 61
6409607 1983
39
Hyperlysinemia without clinical findings. 61
6798824 1981
40
Lysine intolerance in a variant form of citrullinemia. 61
503639 1979
41
[Hyperlysinemia and lysine intolerance]. 61
691354 1978
42
[Familial hyperlysinemia with mental retardation, convulsion & muscular hypertonia (author's transl)]. 61
923176 1977
43
Periodic hyperammonemia, hyperlysinemia, and homocitrullinuria associated with decreased argininosuccinate synthetase and arginase activities. 61
904980 1977
44
[Hereditary persistant hyperlysinemia]. 61
607472 1977
45
Propionic acidemia and hyperlysinemia in a case with ornithine transcarbamylase (OTC) deficiency. 61
977722 1976
46
Clinical and biochemical studies on periodic hyperammonemia with hyperlysinemia and homocitrullinuria. 61
982431 1976
47
[Hyperlysinemia]. 61
1238968 1975
48
Effects of experimentally induced hyperlysinemia on maze learning in mice. 61
4795484 1973
49
Effects of supersuppressor genes on enzymes controlling lysine biosynthesis in Saccharomyces. 61
5411748 1970
50
Excretion of pipecolic acid by infants and by patients with hyperlysinemia. 61
5417004 1970

Variations for Hyperlysinemia, Type I

ClinVar genetic disease variations for Hyperlysinemia, Type I:

6 (show all 15)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AASS NM_005763.4(AASS):c.1601_1609del (p.Cys534_Glu537delinsTer) Deletion Pathogenic 5209 rs387906333 GRCh37: 7:121738550-121738558
GRCh38: 7:122098496-122098504
2 AASS NM_005763.4(AASS):c.2662+1_2662+5delinsTT Indel Pathogenic 100642 rs587777121 GRCh37: 7:121717887-121717891
GRCh38: 7:122077833-122077837
3 AASS NM_005763.4(AASS):c.874A>G (p.Ile292Val) SNV Pathogenic 100643 rs587777122 GRCh37: 7:121756707-121756707
GRCh38: 7:122116653-122116653
4 AASS NM_005763.4(AASS):c.976_977del (p.Gln326fs) Deletion Pathogenic 100644 rs587777123 GRCh37: 7:121755194-121755195
GRCh38: 7:122115140-122115141
5 AASS NM_005763.4(AASS):c.1925C>G (p.Ser642Ter) SNV Pathogenic 100645 rs587777124 GRCh37: 7:121731848-121731848
GRCh38: 7:122091794-122091794
6 AASS NM_005763.4(AASS):c.194G>A (p.Arg65Gln) SNV Pathogenic 100646 rs587777125 GRCh37: 7:121773587-121773587
GRCh38: 7:122133533-122133533
7 AASS NM_005763.4(AASS):c.1256T>G (p.Leu419Arg) SNV Pathogenic 100647 rs587777126 GRCh37: 7:121753194-121753194
GRCh38: 7:122113140-122113140
8 AASS NM_005763.4(AASS):c.2076dup (p.Pro693fs) Duplication Pathogenic 997614 GRCh37: 7:121726173-121726174
GRCh38: 7:122086119-122086120
9 AASS NM_005763.4(AASS):c.125_132del (p.Leu42fs) Deletion Pathogenic 1030963 GRCh37: 7:121773649-121773656
GRCh38: 7:122133595-122133602
10 AASS NM_005763.4(AASS):c.1767-1G>A SNV Likely pathogenic 1030964 GRCh37: 7:121733006-121733006
GRCh38: 7:122092952-122092952
11 AASS NM_005763.4(AASS):c.3G>A (p.Met1Ile) SNV Likely pathogenic 1048521 GRCh37: 7:121773778-121773778
GRCh38: 7:122133724-122133724
12 AASS NM_005763.4(AASS):c.395G>A (p.Arg132His) SNV Likely pathogenic 1048522 GRCh37: 7:121766506-121766506
GRCh38: 7:122126452-122126452
13 AASS NM_005763.4(AASS):c.2762A>G (p.Gln921Arg) SNV Uncertain significance 252652 rs140285200 GRCh37: 7:121716562-121716562
GRCh38: 7:122076508-122076508
14 AASS NM_005763.4(AASS):c.1048G>A (p.Val350Met) SNV Uncertain significance 973452 GRCh37: 7:121753770-121753770
GRCh38: 7:122113716-122113716
15 AASS NM_005763.4(AASS):c.1876A>G (p.Ile626Val) SNV Uncertain significance 973464 GRCh37: 7:121731897-121731897
GRCh38: 7:122091843-122091843

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:

36
# 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 10.42 DHTKD1 AASS

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 mitochondrial matrix GO:0005759 9.43 SUOX PRODH NADK2 DHTKD1 DECR1 AASS
2 mitochondrion GO:0005739 9.28 SUOX SLC25A18 SCCPDH PRODH NDUFS6 NADK2

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

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.17 SUOX SCCPDH PRODH NDUFS6 DHTKD1 DECR1

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.1 SUOX SCCPDH PRODH DHTKD1 DECR1 AASS

Sources for Hyperlysinemia, Type I

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
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