HYPLYS1
MCID: HYP769
MIFTS: 43

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 56 71
Hyperlysinemia 56 12 74 52 25 58 36 29 13 6 15 39
Lysine Intolerance 56 52 73 71
Alpha-Aminoadipic Semialdehyde Synthase Deficiency 56 52 73
Lysine Alpha-Ketoglutarate Reductase Deficiency Disease 25 71
Alpha-Aminoadipic Semialdehyde Deficiency Disease 25 71
Lysine:alpha-Ketoglutarate Reductase Deficiency 56 73
Lysine Alpha-Ketoglutarate Reductase Deficiency 52 58
L-Lysine:nad-Oxido-Reductase Deficiency 56 73
Hyperlysinemia Type I 58 73
Saccharopinuria 25 71
Hyperlysinemias 43 71
Saccharopine Dehydrogenase Deficiency Disease 25
L-Lysine Nad-Oxido-Reductase Deficiency 52
Saccharopine Dehydrogenase Deficiency 71
Familial Hyperlysinemia 25
Hyperlysinemia, 1 73
Hyplys1 73

Characteristics:

Orphanet epidemiological data:

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

OMIM:

56
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 56 238700
KEGG 36 H00188
MeSH 43 D020167
NCIt 49 C123433
SNOMED-CT 67 58558003
ICD10 32 E72.3
MESH via Orphanet 44 D020167
ICD10 via Orphanet 33 E72.3
UMLS via Orphanet 72 C0268553 C0936256
Orphanet 58 ORPHA2203
UMLS 71 C0268553 C0268556 C0543533 more

Summaries for Hyperlysinemia, Type I

OMIM : 56 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 2,4-dienoyl-coa reductase deficiency and hyperlysinemia due to defect in lysine transport into mitochondria, 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 Metabolism. Affiliated tissues include cortex, brain and kidney, and related phenotypes are intellectual disability and seizures

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

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.

NIH Rare Diseases : 52 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 : 73 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 : 74 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 39)
# Related Disease Score Top Affiliating Genes
1 2,4-dienoyl-coa reductase deficiency 33.4 NADK2 DECR1 AASS
2 hyperlysinemia due to defect in lysine transport into mitochondria 12.2
3 saccharopinuria 12.1
4 hyperlysinuria with hyperammonemia 11.2
5 carbonic anhydrase va deficiency, hyperammonemia due to 10.4
6 argininemia 10.3
7 orotic aciduria 10.3
8 cystinuria 10.2
9 purine-pyrimidine metabolic disorder 10.2 SUOX PRODH
10 xanthinuria 10.2 SUOX PRODH
11 argininosuccinic aciduria 10.1
12 ocular motor apraxia 10.1
13 propionic acidemia 10.1
14 reye syndrome 10.1
15 lactic acidosis 10.1
16 spastic paraparesis 10.1
17 hypertonia 10.1
18 multiple acyl-coa dehydrogenase deficiency 10.1 PRODH NADK2 DECR1
19 holocarboxylase synthetase deficiency 10.0 SUOX PC
20 urea cycle disorder 10.0 PRODH PC
21 biotinidase deficiency 9.9 SUOX PC
22 d-2-hydroxyglutaric aciduria 1 9.9 SUOX L2HGDH
23 peroxisome biogenesis disorder 1b 9.9 SUOX PEX19 AASS
24 multiple carboxylase deficiency 9.9 SUOX PC
25 citrullinemia, classic 9.9
26 citrullinemia, type ii, adult-onset 9.9
27 methylmalonic acidemia 9.9
28 isolated methylmalonic acidemia 9.9
29 pyruvate dehydrogenase e1-alpha deficiency 9.9 SUOX PC
30 ectopia lentis 2, isolated, autosomal recessive 9.8 SUOX ADAMTSL4
31 ectopia lentis 1, isolated, autosomal dominant 9.8 SUOX ADAMTSL4
32 glycine encephalopathy 9.8 SUOX PRODH
33 amino acid metabolic disorder 9.7 PRODH L2HGDH
34 isolated ectopia lentis 9.7 SUOX ADAMTSL4
35 l-2-hydroxyglutaric aciduria 9.7 SUOX SCCPDH L2HGDH
36 2-hydroxyglutaric aciduria 9.7 SUOX SCCPDH L2HGDH
37 zellweger syndrome 9.7 SUOX PEX19 AASS AASDH
38 weill-marchesani syndrome 9.6 SUOX ADAMTSL4
39 lens subluxation 9.5 SUOX PEX19 ADAMTSL4

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 seizures 31 HP:0001250
3 muscular hypotonia 31 HP:0001252
4 delayed speech and language development 31 HP:0000750
5 cognitive impairment 31 HP:0100543
6 intellectual disability, mild 31 HP:0001256
7 anemia 31 HP:0001903
8 hyperactivity 31 HP:0000752
9 ectopia lentis 31 HP:0001083
10 short attention span 31 HP:0000736
11 abnormality of the genitourinary system 31 HP:0000119
12 hyperlysinemia 31 HP:0002161

Symptoms via clinical synopsis from OMIM:

56
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

UMLS symptoms related to Hyperlysinemia, Type I:


seizures

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

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-11 9.53 ADAMTSL4
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 9.53 DHTKD1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.53 PRODH
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.53 PRODH
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-206 9.53 DHTKD1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 9.53 ADAMTSL4
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-33 9.53 PRODH
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-34 9.53 ADAMTSL4
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.53 PRODH
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-58 9.53 PRODH
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-66 9.53 PRODH
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.53 DHTKD1
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-86 9.53 ADAMTSL4 DHTKD1 PRODH
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.53 ADAMTSL4

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

Anatomical Context for Hyperlysinemia, Type I

MalaCards organs/tissues related to Hyperlysinemia, Type I:

40
Cortex, Brain, Kidney, Liver

Publications for Hyperlysinemia, Type I

Articles related to Hyperlysinemia, Type I:

(show top 50) (show all 54)
# Title Authors PMID Year
1
Clinical, biochemical, molecular and therapeutic aspects of 2 new cases of 2-aminoadipic semialdehyde synthase deficiency. 61 56 6
23890588 2013
2
Genetic basis of hyperlysinemia. 61 56 6
23570448 2013
3
Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia. 61 56 6
10775527 2000
4
Multiple enzyme defects in familial hyperlysinemia. 61 56 6
934735 1976
5
Familial hyperlysinemias. Purification and characterization of the bifunctional aminoadipic semialdehyde synthase with lysine-ketoglutarate reductase and saccharopine dehydrogenase activities. 61 56
6434529 1984
6
The prognosis of hyperlysinemia: an interim report. 61 56
6407303 1983
7
Hyperlysinemia with saccharopinuria due to combined lysine-ketoglutarate reductase and saccharopine dehydrogenase deficiencies presenting as cystinuria. 61 56
571908 1979
8
Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology. 61 56
463877 1979
9
Excretion of hypusine by children and by patients with familial hyperlysinemia. 61 56
4753051 1973
10
Ocular manifestations of familial hyperlysinemia. 61 56
5557172 1971
11
Familial hyperlysinemia with lysine-ketoglutarate reductase insufficiency. 61 56
5796356 1969
12
Hyperlysinemia associated with retardation. 61 56
5825685 1965
13
HYPERLYSINEMIA. 61 56
14209691 1964
14
Saccharopinuria: a new inborn error of lysine metabolism. 56
5690339 1968
15
Lysine intolerance with periodic ammonia intoxication. 56
6015890 1967
16
The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis. 61
30573525 2019
17
Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant. 61
29388319 2018
18
Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. 61
24847004 2014
19
Pipecolic acid induces oxidative stress in vitro in cerebral cortex of young rats and the protective role of lipoic acid. 61
24338030 2014
20
Neurochemical evidence that lysine inhibits synaptic Na+,K+-ATPase activity and provokes oxidative damage in striatum of young rats in vivo. 61
20976553 2011
21
Inhibition of creatine kinase activity by lysine in rat cerebral cortex. 61
19370404 2009
22
Alpha-aminoadipate delta-semialdehyde synthase mRNA knockdown reduces the lysine requirement of a mouse hepatic cell line. 61
18936211 2008
23
Lysine induces lipid and protein damage and decreases reduced glutathione concentrations in brain of young rats. 61
18691648 2008
24
Plasma lysine concentration and availability of 2-ketoglutarate in liver mitochondria. 61
11999975 2002
25
[Familial hyperlysinemia(alpha-aminoadipic semialdehyde synthase defect)]. 61
9590024 1998
26
[Saccharopinuria (a variant form of familial hyperlysinemia)]. 61
9590025 1998
27
L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients. 61
9187477 1997
28
Familial hyperlysinemia in a patient presenting with progressive spastic paraparesis. 61
8797497 1996
29
[Inborn errors of lysine metabolism]. 61
1904694 1991
30
[Hyperlysinemia and hyperammonemia]. 61
1904697 1991
31
2,4-Dienoyl-coenzyme A reductase deficiency: a possible new disorder of fatty acid oxidation. 61
2332510 1990
32
Lysine transport in human kidney. 61
2112825 1990
33
The significance of hyperpipecolatemia in Zellweger syndrome. 61
3087161 1986
34
Biochemical and histologic pathology in an infant with cross-reacting material (negative) pyruvate carboxylase deficiency. 61
3085060 1986
35
The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency. 61
6424438 1984
36
[A patient with persistent hyperlysinemia]. 61
6407142 1983
37
Separation of ornithine and lysine activities of the ornithine-transcarbamylase-catalyzed reaction. 61
6409607 1983
38
Hyperlysinemia without clinical findings. 61
6798824 1981
39
Lysine intolerance in a variant form of citrullinemia. 61
503639 1979
40
[Hyperlysinemia and lysine intolerance]. 61
691354 1978
41
[Familial hyperlysinemia with mental retardation, convulsion & muscular hypertonia (author's transl)]. 61
923176 1977
42
Periodic hyperammonemia, hyperlysinemia, and homocitrullinuria associated with decreased argininosuccinate synthetase and arginase activities. 61
904980 1977
43
[Hereditary persistant hyperlysinemia]. 61
607472 1977
44
Propionic acidemia and hyperlysinemia in a case with ornithine transcarbamylase (OTC) deficiency. 61
977722 1976
45
Clinical and biochemical studies on periodic hyperammonemia with hyperlysinemia and homocitrullinuria. 61
982431 1976
46
[Hyperlysinemia]. 61
1238968 1975
47
Effects of experimentally induced hyperlysinemia on maze learning in mice. 61
4795484 1973
48
Excretion of pipecolic acid by infants and by patients with hyperlysinemia. 61
5417004 1970
49
Effects of supersuppressor genes on enzymes controlling lysine biosynthesis in Saccharomyces. 61
5411748 1970
50
Paths of lysine degradation in patients with hyperlysinemia. 61
6074139 1967

Variations for Hyperlysinemia, Type I

ClinVar genetic disease variations for Hyperlysinemia, Type I:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AASS NM_005763.4(AASS):c.1601_1609del (p.Cys534_Glu537delinsTer)deletion Pathogenic 5209 rs387906333 7:121738550-121738558 7:122098496-122098504
2 AASS NM_005763.4(AASS):c.2662+1_2662+5delinsTTindel Pathogenic 100642 rs587777121 7:121717887-121717891 7:122077833-122077837
3 AASS NM_005763.4(AASS):c.874A>G (p.Ile292Val)SNV Pathogenic 100643 rs587777122 7:121756707-121756707 7:122116653-122116653
4 AASS NM_005763.4(AASS):c.976_977del (p.Gln326fs)deletion Pathogenic 100644 rs587777123 7:121755194-121755195 7:122115140-122115141
5 AASS NM_005763.4(AASS):c.1925C>G (p.Ser642Ter)SNV Pathogenic 100645 rs587777124 7:121731848-121731848 7:122091794-122091794
6 AASS NM_005763.4(AASS):c.194G>A (p.Arg65Gln)SNV Pathogenic 100646 rs587777125 7:121773587-121773587 7:122133533-122133533
7 AASS NM_005763.4(AASS):c.1256T>G (p.Leu419Arg)SNV Pathogenic 100647 rs587777126 7:121753194-121753194 7:122113140-122113140
8 AASS NM_005763.4(AASS):c.2762A>G (p.Gln921Arg)SNV Uncertain significance 252652 rs140285200 7:121716562-121716562 7:122076508-122076508

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
Show member pathways
12.93 SUOX PRODH PC NDUFS6 NADK2 L2HGDH
2 10.94 DHTKD1 AASS
3 10.3 PC DECR1

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 9.61 SUOX SCCPDH PRODH PC NADK2 L2HGDH
2 mitochondrial matrix GO:0005759 9.17 SUOX PRODH PC NADK2 DHTKD1 DECR1

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 9.23 SUOX SCCPDH PRODH NDUFS6 L2HGDH DHTKD1
2 fatty acid metabolic process GO:0006631 9.13 NDUFS6 DECR1 AASDH

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 9.17 SUOX SCCPDH PRODH L2HGDH DHTKD1 DECR1

Sources for Hyperlysinemia, Type I

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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