HYXKY
MCID: HYD030
MIFTS: 27

Hydroxykynureninuria (HYXKY)

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

Aliases & Classifications for Hydroxykynureninuria

MalaCards integrated aliases for Hydroxykynureninuria:

Name: Hydroxykynureninuria 57 12 20 58 72 36 29 54 6 39 70
Xanthurenic Aciduria 57 12 20 58 72
Kynureninase Deficiency 12 20 58
Kynureninase Deficiency, Partial 57
Partial Kynureninase Deficiency 72
Hyxky 72

Characteristics:

Orphanet epidemiological data:

58
hydroxykynureninuria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
hydroxykynureninuria:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Hydroxykynureninuria

KEGG : 36 Hydroxykynureninuria, also known as xanthurenic aciduria is autosomal recessive disorder of tryptophan metabolism. It is characterized by excessive output of xanthutrenic acid, 3-hydroxykynurenine, and kynurenine in urine. This disease is caused by homozygous mutation in the KYNU gene, which encodes kynureninase. Kynureninase is an enzyme in the catabolic pathway of tryptophan metabolism. Some of these deficiencies lead to pellagra or mild pellagra-like symptoms, while it was reported in some patients no symptom of niacin deficiency was observed. The different clinical outcomes could be explained by differences in the intake of niacin. The sufficient intake of niacin could prevent depletion in some patients despite their impaired niacin synthesis.

MalaCards based summary : Hydroxykynureninuria, also known as xanthurenic aciduria, is related to vertebral, cardiac, renal, and limb defects syndrome 2. An important gene associated with Hydroxykynureninuria is KYNU (Kynureninase), and among its related pathways/superpathways is Tryptophan metabolism. Affiliated tissues include skin, and related phenotypes are encephalopathy and abnormal circulating tryptophan concentration

Disease Ontology : 12 An amino acid metabolic disorder characterized by impaired tryptophan metabolism resulting in high urinary excretion of kynurenine, xanthurenic acid and 3-hydroxykynurenine that has material basis in homozygous or compound heterozygous mutation in KYNU on chromosome 2q22.2.

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79155 Definition A rare, genetic disorder of tryptophan metabolism characterized by massive urinary excretion of xanthurenic acid (XA), 3-hydroxykynurenine and kynurenine and increased XA concentration in plasma. The clinical phenotype is highly variable, ranging from asymptomatic or mild cases presentating with jaundice and vomiting, with subsequent normal development and growth, to more severe cases with manifestions which include intellectual disability, cerebellar ataxia, pellagra, progressive encephalopathy with muscular hypotonia, global developmental delay, stereotyped gestures and/or congenital deafness.

OMIM® : 57 Hydroxykynureninuria, also known as xanthurenicaciduria, is an autosomal recessive condition characterized by high urinary excretion of kynurenine (KYN), xanthurenic acid (XA) and 3-hydroxykynurenine (3-OHKYN), with no detectable anthranilic acid (AA) or 3-hydroxyanthranilic acid (3-OHAA) (Christensen et al., 2007). (236800) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Hydroxykynureninuria: An inborn error of amino acid metabolism characterized by massive urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid. Affected individuals manifest renal tubular dysfunction, metabolic acidosis, psychomotor retardation, non- progressive encephalopathy, and muscular hypertonia.

Related Diseases for Hydroxykynureninuria

Diseases related to Hydroxykynureninuria via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 vertebral, cardiac, renal, and limb defects syndrome 2 11.1

Symptoms & Phenotypes for Hydroxykynureninuria

Human phenotypes related to Hydroxykynureninuria:

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 encephalopathy 58 31 obligate (100%) Obligate (100%) HP:0001298
2 abnormal circulating tryptophan concentration 31 obligate (100%) HP:0004365
3 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
4 hypotension 58 31 frequent (33%) Frequent (79-30%) HP:0002615
5 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
6 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
7 stereotypy 58 31 frequent (33%) Frequent (79-30%) HP:0000733
8 dry skin 58 31 frequent (33%) Frequent (79-30%) HP:0000958
9 headache 58 31 frequent (33%) Frequent (79-30%) HP:0002315
10 congenital sensorineural hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0008527
11 tachycardia 58 31 frequent (33%) Frequent (79-30%) HP:0001649
12 renal tubular acidosis 58 31 frequent (33%) Frequent (79-30%) HP:0001947
13 breathing dysregulation 58 31 frequent (33%) Frequent (79-30%) HP:0005957
14 stomatitis 58 31 frequent (33%) Frequent (79-30%) HP:0010280
15 coma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001259
16 metabolic acidosis 58 31 Frequent (79-30%) HP:0001942
17 hearing impairment 31 HP:0000365
18 renal tubular dysfunction 31 HP:0000124
19 aminoaciduria 31 HP:0003355
20 abnormality of the respiratory system 31 HP:0002086
21 psychomotor retardation 31 HP:0025356
22 abnormality of the musculature 31 HP:0003011
23 progressive encephalopathy 58 Excluded (0%)
24 abnormality of tryptophan metabolism 58 Obligate (100%)
25 nonprogressive encephalopathy 31 HP:0007030

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
G U:
renal tubular dysfunction
renal or metabolic acidosis

Neuro:
psychomotor retardation
coma
nonprogressive encephalopathy
mental retardation
stereotyped gestures

Muscle:
muscular hypertonia

Lab:
kynureninuria
3-hydroxykynureninuria
xanthurenic aciduria
kynureninase deficiency

Cardiac:
tachycardia
arterial hypotension

Ears:
congenital deafness

Respiratory:
irregular breathing

Misc:
both b6-responsive and b6-unresponsive forms are known
neurologic status worsened by viral illness

Clinical features from OMIM®:

236800 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hydroxykynureninuria

Search Clinical Trials , NIH Clinical Center for Hydroxykynureninuria

Genetic Tests for Hydroxykynureninuria

Genetic tests related to Hydroxykynureninuria:

# Genetic test Affiliating Genes
1 Hydroxykynureninuria 29 KYNU

Anatomical Context for Hydroxykynureninuria

MalaCards organs/tissues related to Hydroxykynureninuria:

40
Skin

Publications for Hydroxykynureninuria

Articles related to Hydroxykynureninuria:

(show all 20)
# Title Authors PMID Year
1
Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase. 61 54 6 57
17334708 2007
2
Vitamin B6 dependent xanthurenic aciduria. 61 57
5586569 1967
3
Hydroxykynureninuria. 57 61
6015911 1967
4
HYDROXYKYNURENINURIA: A CASE OF ABNORMAL TRYPTOPHAN METABOLISM PROBABLY DUE TO A DEFICIENCY OF KYNURENINASE. 61 57
14169454 1964
5
Congenital non-progressive encephalopathy and deafness with intermittent episodes of coma and hyperkynureninuria. 57
8830173 1996
6
Lethal familial pellagra-like skin lesion associated with neurologic and developmental impairment and the development of cataracts. 57
4058988 1985
7
Biallelic variants in KYNU cause a multisystemic syndrome with hand hyperphalangism. 61
31923704 2020
8
The chaperone role of the pyridoxal 5'-phosphate and its implications for rare diseases involving B6-dependent enzymes. 61
24355692 2014
9
Amino acid disorders in mental retardation: a two-decade study from Andhra Pradesh. 61
15168722 2004
10
[Nicotinic acid and nicotinamide]. 61
10540864 1999
11
[Kynureninase deficiency]. 54
9590041 1998
12
Tryptophan metabolic studies in patients with presenile cataracts. 61
2282069 1990
13
[Studies of tryptophan metabolism in cancer of the urinary bladder]. 61
2618183 1989
14
[Studies on tryptophan metabolism in calcium oxalate urolithiasis]. 61
3407338 1988
15
[Screening for congenital metabolic diseases in mentally retarded patients in 6 psychiatric institutions of Lower Saxony]. 61
6492685 1984
16
Hydroxykynureninuria, a case report. 61
7152601 1982
17
Familial hydroxykynureninuria. 61
649181 1978
18
[Xanthurenic aciduria as a specific test in dithiocarbamate poisoning]. 61
1254185 1976
19
Vitamin B6 dependent xanthurenic aciduria (the second report). 61
5723199 1968
20
[B6-dependent xanthurenic aciduria]. 61
5749458 1968

Variations for Hydroxykynureninuria

ClinVar genetic disease variations for Hydroxykynureninuria:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KYNU NM_003937.3(KYNU):c.592A>G (p.Thr198Ala) SNV Pathogenic 160355 rs606231307 GRCh37: 2:143718202-143718202
GRCh38: 2:142960633-142960633

UniProtKB/Swiss-Prot genetic disease variations for Hydroxykynureninuria:

72
# Symbol AA change Variation ID SNP ID
1 KYNU p.Thr198Ala VAR_054401 rs606231307

Expression for Hydroxykynureninuria

Search GEO for disease gene expression data for Hydroxykynureninuria.

Pathways for Hydroxykynureninuria

Pathways related to Hydroxykynureninuria according to KEGG:

36
# Name Kegg Source Accession
1 Tryptophan metabolism hsa00380

GO Terms for Hydroxykynureninuria

Sources for Hydroxykynureninuria

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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