MCID: HST006
MIFTS: 45

Histidinemia

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

Aliases & Classifications for Histidinemia

MalaCards integrated aliases for Histidinemia:

Name: Histidinemia 57 12 76 53 25 59 75 37 29 55 6 15 40 73
Histidine Ammonia-Lyase Deficiency 57 53 25 59
Histidase Deficiency 57 53 25 59
Hal Deficiency 57 53 25 59
His Deficiency 57 53 25 59
Hyperhistidinemia 25 59
Histidinuria 12 59
Histidinuria Renal Tubular Defect 73
Histidine Ammonia-Lyase 13
Histid 75

Characteristics:

Orphanet epidemiological data:

59
histidinemia
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe),1-9/100000 (United States),1-5/10000 (Japan); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
generally considered to be a benign disorder
high prevalence in japan
one compound heterozygous patient reported (last curated february 2015)
relationship of rare neuropsychiatric signs to histidinemia is unclear



Classifications:

Orphanet: 59  
Inborn errors of metabolism


External Ids:

OMIM 57 235800
Disease Ontology 12 DOID:0060168
Orphanet 59 ORPHA2157
UMLS via Orphanet 74 C0268642 C0220992
ICD10 via Orphanet 34 E70.8
MESH via Orphanet 45 C538320
MedGen 42 C0220992
KEGG 37 H00171

Summaries for Histidinemia

NIH Rare Diseases : 53 Histidinemia is an inherited metabolic condition characterized by elevated levels of the amino acid histidine in blood, urine, and cerebrospinal fluid. In most cases, people with this condition have no health problems and may not even know that they are affected. Individuals with histidinemia who also experience a medical complication during or shortly after birth (such as a temporary lack of oxygen), may be at an increased risk of developing intellectual disability, behavioral problems, or learning disabilities. Histidinemia is caused by changes (mutations) in the HAL gene. This gene provides instructions for making an enzyme called histidase, which breaks down histidine into a molecule called urocanic acid. If histidase doesn't do its job properly, histidine levels become elevated. Histidinemia is inherited in an autosomal recessive pattern. Because there are no symptoms associated with this condition, treatment is not necessary.

MalaCards based summary : Histidinemia, also known as histidine ammonia-lyase deficiency, is related to histidinuria renal tubular defect and histidinuria due to a renal tubular defect. An important gene associated with Histidinemia is HAL (Histidine Ammonia-Lyase), and among its related pathways/superpathways are Histidine metabolism and NRF2 pathway. Affiliated tissues include skin and testes, and related phenotypes are behavioral abnormality and intellectual disability

Disease Ontology : 12 A histidine metabolism disease characterized by a deficiency of the enzyme histidase.

Genetics Home Reference : 25 Histidinemia is an inherited condition characterized by elevated blood levels of the amino acid histidine, a building block of most proteins. Histidinemia is caused by the shortage (deficiency) of the enzyme that breaks down histidine. Histidinemia typically causes no health problems, and most people with elevated histidine levels are unaware that they have this condition.

OMIM : 57 Histidinemia is a metabolic disorder characterized by increased levels of histidine in blood, urine, and cerebrospinal fluid, and decreased levels of the metabolite urocanic acid in blood, urine, and skin cells. Although histidinemia was originally associated with mental retardation and speech defects, it is generally considered to be a benign disorder (Levy et al., 2001). However, it is possible that histidinemia may be a risk factor for developmental disorders in certain individuals under specific circumstances, such as perinatal events (Ishikawa, 1987). (235800)

UniProtKB/Swiss-Prot : 75 Histidinemia: Autosomal recessive disease characterized by increased histidine and histamine as well as decreased urocanic acid in body fluids.

Wikipedia : 76 Histidinemia, also referred to as histidinuria, is a rare autosomal recessive metabolic disorder caused... more...

Related Diseases for Histidinemia

Graphical network of the top 20 diseases related to Histidinemia:



Diseases related to Histidinemia

Symptoms & Phenotypes for Histidinemia

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin:
decreased histidase activity
decreased urocanic acid in stratum corneum

Neurologic Behavioral Psychiatric Manifestations:
behavioral disorders (rare)

Neurologic Central Nervous System:
mental retardation (rare less than 1% of cases)
speech disorders (rare)

Laboratory Abnormalities:
increased histidine in blood, urine, and csf
decreased or absent histidase activity
decreased urocanic acid in blood, urine, and skin cells


Clinical features from OMIM:

235800

Human phenotypes related to Histidinemia:

32
# Description HPO Frequency HPO Source Accession
1 behavioral abnormality 32 occasional (7.5%) HP:0000708
2 intellectual disability 32 very rare (1%) HP:0001249
3 neurological speech impairment 32 occasional (7.5%) HP:0002167
4 histidinuria 32 HP:0002927
5 hyperhistidinemia 32 HP:0010906

MGI Mouse Phenotypes related to Histidinemia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 9.17 CEBPB CTH GGT1 HAL PLG PPOX

Drugs & Therapeutics for Histidinemia

Search Clinical Trials , NIH Clinical Center for Histidinemia

Genetic Tests for Histidinemia

Genetic tests related to Histidinemia:

# Genetic test Affiliating Genes
1 Histidinemia 29 HAL

Anatomical Context for Histidinemia

MalaCards organs/tissues related to Histidinemia:

41
Skin, Testes

Publications for Histidinemia

Articles related to Histidinemia:

(show top 50) (show all 81)
# Title Authors Year
1
Nano optical probe samarium tetracycline complex for early diagnosis of histidinemia in new born children. ( 28262611 )
2017
2
The lure of treatment: expanded newborn screening and the curious case of histidinemia. ( 20156889 )
2010
3
Inhibition of histidine ammonia lyase by heteroaryl-alanines and acrylates. ( 17193285 )
2006
4
Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene. ( 15806399 )
2005
5
Autocatalytic peptide cyclization during chain folding of histidine ammonia-lyase. ( 11796111 )
2002
6
Structures of two histidine ammonia-lyase modifications and implications for the catalytic mechanism. ( 11895450 )
2002
7
Computational analysis of the autocatalytic posttranslational cyclization observed in histidine ammonia-lyase. A comparison with green fluorescent protein. ( 11457276 )
2001
8
On the nature of the irreversible inhibition of histidine ammonia lyase by cysteine and dioxygen. ( 8831970 )
1996
9
Pharmacokinetics of stable isotopically labeled L-histidine in humans and the assessment of in vivo histidine ammonia lyase activities. ( 8825190 )
1996
10
Histidinemia in mice: a metabolic defect treated using a novel approach to hepatocellular transplantation. ( 7537713 )
1995
11
Long-term follow-up of 58 patients with histidinemia treated with a histidine-restricted diet: no effect of therapy. ( 7971002 )
1994
12
Identification of the mutation in murine histidinemia (his) and genetic mapping of the murine histidase locus (Hal) on chromosome 10. ( 8486363 )
1993
13
Inactivation of histidine ammonia-lyase from Streptomyces griseus by dicarbonyl reagents. ( 8507666 )
1993
14
Histidinemia: a biochemical variant or a disease? ( 8463510 )
1993
15
Reversible stepwise mechanism involving a carbanion intermediate in the elimination of ammonia from L-histidine catalyzed by histidine ammonia-lyase. ( 1618765 )
1992
16
Reversible reaction via a carbanion intermediate in the elimination of ammonia from L-histidine catalysed by histidine ammonia-lyase. ( 1902841 )
1991
17
Histidase and histidinemia. Clinical and molecular considerations. ( 1943682 )
1991
18
Biochemical investigation of histidinemia in schizophrenic patients. ( 2297554 )
1990
19
Characterization of L-histidine ammonia-lyase immobilized by microencapsulation in artificial cells: preparation, kinetics, stability, and in vitro depletion of histidine. ( 2347667 )
1990
20
Hyperhistaminemia in patients with histidinemia due to increased decarboxylation of histidine. ( 2482142 )
1989
21
Joubert's syndrome associated with congenital ocular fibrosis and histidinemia. ( 2469414 )
1989
22
Developmental disorders in histidinemia--follow-up study of language development in histidinemia. ( 2472732 )
1987
23
Speech disorders associated with histidinemia and other hereditary disorders of amino acid metabolism. ( 3710332 )
1986
24
Formation of N tau-ribosylhistidine, a novel histidine derivative found in the urine in histidinemia, from histidine and NAD(P)+ catalyzed by an NAD(P)+ glycohydrolase system. ( 2992472 )
1985
25
Genetic heterogeneity of histidinemia detected by screening newborn infants in Japan. ( 3836313 )
1985
26
Histamine metabolism in patients with histidinemia: determination of urinary levels of histamine, N tau-methylhistamine, imidazole acetic acid, and its conjugate(s). ( 6530403 )
1984
27
Histidinemia. A case with resolution of myoclonic seizures after treatment with a low-histidine diet. ( 6823923 )
1983
28
Intellectual development in patients with untreated histidinemia. A collaborative study group of neonatal screening for inborn errors of metabolism in Japan. ( 7119955 )
1982
29
Comparison of the properties of histidine ammonia-lyase in normal and histidinemic mutant mice. ( 7103928 )
1982
30
Skin histidase activity and urine formiminoglutamic acid (FIGLU) in patients with histidinemia found by screening newborn infants. ( 7067128 )
1982
31
[Clinical studies of histidinemia (author's transl)]. ( 6790399 )
1981
32
Histidinemia: biochemistry and behavior. ( 7211773 )
1981
33
Histidinemia: biochemical parameters for diagnosis. ( 7211776 )
1981
34
Relationship between skin histidase activity and blood histidine response to histidine intake in patients with histidinemia. ( 7400897 )
1980
35
Serotonin in experimental histidinemia. ( 7464987 )
1980
36
Histidinemia and infantile autism. ( 438113 )
1979
37
The nutritional therapy of histidinemia. ( 490237 )
1979
38
A new sensitive method for assay of histidase in human skin and detection of heterozygotes for histidinemia. ( 476954 )
1979
39
Sibship with histidinemia and an unrelated encephalopathy. Clinical and biochemical studies. ( 617985 )
1977
40
Deficits in discrimination and maze learning resulting from maternal histidinemia in rats. ( 563880 )
1977
41
Studies on the production and assessment of experimental histidinemia in the rat. ( 8133 )
1976
42
Histidinemia produced in the rat by treatment with nitromethane1. ( 1178145 )
1975
43
Histidinemia with features of the Marfan syndrome. ( 1127531 )
1975
44
Histidinemia. Classical and atypical form in siblings. ( 1146783 )
1975
45
Infantile spasms associated with histidinemia. ( 1167649 )
1975
46
Histidinemia and "normohistidinemic histidinuria". Report of three cases and the effect of different protein intakes on urinary excretion of histidine. ( 4820585 )
1974
47
Routine newborn screening for histidinemia. Clinical and biochemical results. ( 4421298 )
1974
48
Histidinemia. ( 4453360 )
1974
49
Histidinemia. Report of a case. ( 4443038 )
1974
50
The use of histidase for the study of amniotic cell origin and histidinemia. ( 4126443 )
1973

Variations for Histidinemia

UniProtKB/Swiss-Prot genetic disease variations for Histidinemia:

75
# Symbol AA change Variation ID SNP ID
1 HAL p.Arg206Thr VAR_022915 rs121434327
2 HAL p.Arg208Leu VAR_022916 rs121434328
3 HAL p.Pro259Leu VAR_022917 rs121434329
4 HAL p.Arg322Pro VAR_022918 rs121434330

ClinVar genetic disease variations for Histidinemia:

6
(show top 50) (show all 132)
# Gene Variation Type Significance SNP ID Assembly Location
1 HAL NM_002108.3(HAL): c.*1518C> T single nucleotide variant Uncertain significance rs148189130 GRCh38 Chromosome 12, 95972714: 95972714
2 HAL NM_002108.3(HAL): c.*1518C> T single nucleotide variant Uncertain significance rs148189130 GRCh37 Chromosome 12, 96366492: 96366492
3 HAL NM_002108.3(HAL): c.*617G> A single nucleotide variant Uncertain significance rs113875416 GRCh38 Chromosome 12, 95973615: 95973615
4 HAL NM_002108.3(HAL): c.*617G> A single nucleotide variant Uncertain significance rs113875416 GRCh37 Chromosome 12, 96367393: 96367393
5 HAL NM_002108.3(HAL): c.*603A> G single nucleotide variant Uncertain significance rs886049898 GRCh37 Chromosome 12, 96367407: 96367407
6 HAL NM_002108.3(HAL): c.*603A> G single nucleotide variant Uncertain significance rs886049898 GRCh38 Chromosome 12, 95973629: 95973629
7 HAL NM_002108.3(HAL): c.*132C> T single nucleotide variant Uncertain significance rs140039557 GRCh37 Chromosome 12, 96367878: 96367878
8 HAL NM_002108.3(HAL): c.*132C> T single nucleotide variant Uncertain significance rs140039557 GRCh38 Chromosome 12, 95974100: 95974100
9 HAL NM_002108.3(HAL): c.1793C> T (p.Pro598Leu) single nucleotide variant Uncertain significance rs143935341 GRCh37 Chromosome 12, 96370247: 96370247
10 HAL NM_002108.3(HAL): c.1793C> T (p.Pro598Leu) single nucleotide variant Uncertain significance rs143935341 GRCh38 Chromosome 12, 95976469: 95976469
11 HAL NM_002108.3(HAL): c.1763+9A> C single nucleotide variant Uncertain significance rs201942023 GRCh38 Chromosome 12, 95976589: 95976589
12 HAL NM_002108.3(HAL): c.1763+9A> C single nucleotide variant Uncertain significance rs201942023 GRCh37 Chromosome 12, 96370367: 96370367
13 HAL NM_002108.3(HAL): c.1414G> A (p.Glu472Lys) single nucleotide variant Uncertain significance rs147706824 GRCh38 Chromosome 12, 95980661: 95980661
14 HAL NM_002108.3(HAL): c.1414G> A (p.Glu472Lys) single nucleotide variant Uncertain significance rs147706824 GRCh37 Chromosome 12, 96374439: 96374439
15 HAL NM_002108.3(HAL): c.1315G> A (p.Val439Ile) single nucleotide variant Benign rs7297245 GRCh38 Chromosome 12, 95980836: 95980836
16 HAL NM_002108.3(HAL): c.1315G> A (p.Val439Ile) single nucleotide variant Benign rs7297245 GRCh37 Chromosome 12, 96374614: 96374614
17 HAL NM_002108.3(HAL): c.904-5G> A single nucleotide variant Uncertain significance rs189938038 GRCh38 Chromosome 12, 95987219: 95987219
18 HAL NM_002108.3(HAL): c.904-5G> A single nucleotide variant Uncertain significance rs189938038 GRCh37 Chromosome 12, 96380997: 96380997
19 HAL NM_002108.3(HAL): c.841G> A (p.Ala281Thr) single nucleotide variant Uncertain significance rs140891326 GRCh38 Chromosome 12, 95990407: 95990407
20 HAL NM_002108.3(HAL): c.841G> A (p.Ala281Thr) single nucleotide variant Uncertain significance rs140891326 GRCh37 Chromosome 12, 96384185: 96384185
21 HAL NM_002108.3(HAL): c.322C> T (p.Arg108Trp) single nucleotide variant Uncertain significance rs143854097 GRCh38 Chromosome 12, 95994812: 95994812
22 HAL NM_002108.3(HAL): c.322C> T (p.Arg108Trp) single nucleotide variant Uncertain significance rs143854097 GRCh37 Chromosome 12, 96388590: 96388590
23 HAL NM_002108.3(HAL): c.276C> T (p.Asp92=) single nucleotide variant Uncertain significance rs151299220 GRCh38 Chromosome 12, 95994965: 95994965
24 HAL NM_002108.3(HAL): c.276C> T (p.Asp92=) single nucleotide variant Uncertain significance rs151299220 GRCh37 Chromosome 12, 96388743: 96388743
25 HAL NM_002108.3(HAL): c.-68G> A single nucleotide variant Uncertain significance rs565607247 GRCh38 Chromosome 12, 95995978: 95995978
26 HAL NM_002108.3(HAL): c.-68G> A single nucleotide variant Uncertain significance rs565607247 GRCh37 Chromosome 12, 96389756: 96389756
27 HAL NM_002108.3(HAL): c.-108C> T single nucleotide variant Uncertain significance rs886049903 GRCh38 Chromosome 12, 95996104: 95996104
28 HAL NM_002108.3(HAL): c.-108C> T single nucleotide variant Uncertain significance rs886049903 GRCh37 Chromosome 12, 96389882: 96389882
29 HAL NM_002108.3(HAL): c.*1499A> G single nucleotide variant Likely benign rs3812807 GRCh38 Chromosome 12, 95972733: 95972733
30 HAL NM_002108.3(HAL): c.*1499A> G single nucleotide variant Likely benign rs3812807 GRCh37 Chromosome 12, 96366511: 96366511
31 HAL NM_002108.3(HAL): c.*1409G> A single nucleotide variant Uncertain significance rs141219113 GRCh38 Chromosome 12, 95972823: 95972823
32 HAL NM_002108.3(HAL): c.*1409G> A single nucleotide variant Uncertain significance rs141219113 GRCh37 Chromosome 12, 96366601: 96366601
33 HAL NM_002108.3(HAL): c.*1312C> T single nucleotide variant Likely benign rs1059845 GRCh38 Chromosome 12, 95972920: 95972920
34 HAL NM_002108.3(HAL): c.*1312C> T single nucleotide variant Likely benign rs1059845 GRCh37 Chromosome 12, 96366698: 96366698
35 HAL NM_002108.3(HAL): c.*1241A> C single nucleotide variant Benign rs1059844 GRCh38 Chromosome 12, 95972991: 95972991
36 HAL NM_002108.3(HAL): c.*1241A> C single nucleotide variant Benign rs1059844 GRCh37 Chromosome 12, 96366769: 96366769
37 HAL NM_002108.3(HAL): c.*1178A> G single nucleotide variant Uncertain significance rs886049895 GRCh38 Chromosome 12, 95973054: 95973054
38 HAL NM_002108.3(HAL): c.*1178A> G single nucleotide variant Uncertain significance rs886049895 GRCh37 Chromosome 12, 96366832: 96366832
39 HAL NM_002108.3(HAL): c.*1169G> T single nucleotide variant Uncertain significance rs745355227 GRCh38 Chromosome 12, 95973063: 95973063
40 HAL NM_002108.3(HAL): c.*1169G> T single nucleotide variant Uncertain significance rs745355227 GRCh37 Chromosome 12, 96366841: 96366841
41 HAL NM_002108.3(HAL): c.1764-5T> C single nucleotide variant Uncertain significance rs752249746 GRCh38 Chromosome 12, 95976503: 95976503
42 HAL NM_002108.3(HAL): c.1764-5T> C single nucleotide variant Uncertain significance rs752249746 GRCh37 Chromosome 12, 96370281: 96370281
43 HAL NM_002108.3(HAL): c.921T> C (p.Asn307=) single nucleotide variant Likely benign rs11108364 GRCh38 Chromosome 12, 95987197: 95987197
44 HAL NM_002108.3(HAL): c.921T> C (p.Asn307=) single nucleotide variant Likely benign rs11108364 GRCh37 Chromosome 12, 96380975: 96380975
45 HAL NM_002108.3(HAL): c.855+9C> T single nucleotide variant Uncertain significance rs35144639 GRCh38 Chromosome 12, 95990384: 95990384
46 HAL NM_002108.3(HAL): c.855+9C> T single nucleotide variant Uncertain significance rs35144639 GRCh37 Chromosome 12, 96384162: 96384162
47 HAL NM_002108.3(HAL): c.308+14C> T single nucleotide variant Uncertain significance rs886049902 GRCh38 Chromosome 12, 95994919: 95994919
48 HAL NM_002108.3(HAL): c.308+14C> T single nucleotide variant Uncertain significance rs886049902 GRCh37 Chromosome 12, 96388697: 96388697
49 HAL NM_002108.3(HAL): c.94G> T (p.Val32Leu) single nucleotide variant Uncertain significance rs150051467 GRCh38 Chromosome 12, 95995817: 95995817
50 HAL NM_002108.3(HAL): c.94G> T (p.Val32Leu) single nucleotide variant Uncertain significance rs150051467 GRCh37 Chromosome 12, 96389595: 96389595

Expression for Histidinemia

Search GEO for disease gene expression data for Histidinemia.

Pathways for Histidinemia

Pathways related to Histidinemia according to KEGG:

37
# Name Kegg Source Accession
1 Histidine metabolism hsa00340

Pathways related to Histidinemia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.74 GGT1 SERPINA1 SLC6A18
2
Show member pathways
11.59 GOT2 HAL QDPR
3
Show member pathways
11.52 CTH GOT1 GOT2
4 10.88 CTH GOT1 GOT2 HAL
5
Show member pathways
10.85 GOT1 GOT2
6
Show member pathways
10.71 GOT1 GOT2
7 10.68 ADSL GOT1 GOT2
8
Show member pathways
10.27 GOT1 GOT2

GO Terms for Histidinemia

Biological processes related to Histidinemia according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 cellular amino acid biosynthetic process GO:0008652 9.63 CTH GOT1 GOT2
2 response to muscle activity GO:0014850 9.52 ADSL GOT2
3 2-oxoglutarate metabolic process GO:0006103 9.51 GOT1 GOT2
4 oxaloacetate metabolic process GO:0006107 9.49 GOT1 GOT2
5 aspartate metabolic process GO:0006531 9.48 GOT1 GOT2
6 cysteine biosynthetic process GO:0019344 9.43 CTH GGT1
7 dicarboxylic acid metabolic process GO:0043648 9.4 GOT1 GOT2
8 aspartate catabolic process GO:0006533 9.37 GOT1 GOT2
9 aspartate biosynthetic process GO:0006532 9.32 GOT1 GOT2
10 glutamate catabolic process to aspartate GO:0019550 9.26 GOT1 GOT2
11 glutamate catabolic process to 2-oxoglutarate GO:0019551 9.16 GOT1 GOT2
12 glutamate metabolic process GO:0006536 9.13 GGT1 GOT1 GOT2
13 cellular amino acid metabolic process GO:0006520 8.92 GGT1 GOT1 GOT2 QDPR

Molecular functions related to Histidinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lyase activity GO:0016829 9.5 ADSL CTH HAL
2 transaminase activity GO:0008483 9.26 GOT1 GOT2
3 carboxylic acid binding GO:0031406 9.16 GOT1 GOT2
4 pyridoxal phosphate binding GO:0030170 9.13 CTH GOT1 GOT2
5 L-aspartate:2-oxoglutarate aminotransferase activity GO:0004069 8.62 GOT1 GOT2

Sources for Histidinemia

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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