MCID: HST006
MIFTS: 46

Histidinemia

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

Aliases & Classifications for Histidinemia

MalaCards integrated aliases for Histidinemia:

Name: Histidinemia 53 12 72 49 24 55 71 36 28 51 14 69
Histidine Ammonia-Lyase Deficiency 53 49 24 55
Histidase Deficiency 53 49 24 55
Hal Deficiency 53 49 24 55
His Deficiency 53 49 24 55
Hyperhistidinemia 24 55
Histidinuria 12 55
Histidinuria Renal Tubular Defect 69
Histidine Ammonia-Lyase 13
Histid 71

Characteristics:

Orphanet epidemiological data:

55
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:

53
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: 55  
Inborn errors of metabolism


External Ids:

OMIM 53 235800
Disease Ontology 12 DOID:0060168
Orphanet 55 ORPHA2157
MESH via Orphanet 42 C538320
UMLS via Orphanet 70 C0220992 C0268642
ICD10 via Orphanet 33 E70.8
MedGen 39 C0220992
KEGG 36 H00171

Summaries for Histidinemia

NIH Rare Diseases : 49 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. Last updated: 11/14/2016

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, and has symptoms including intellectual disability, neurological speech impairment and behavioral abnormality. 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 phenotype is renal/urinary system.

OMIM : 53 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 : 71 Histidinemia: Autosomal recessive disease characterized by increased histidine and histamine as well as decreased urocanic acid in body fluids.

Genetics Home Reference : 24 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.

Disease Ontology : 12 A histidine metabolism disease that involves a deficiency of the enzyme histidase.

Wikipedia : 72 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:

53
SkinNailsHairSkin:
decreased histidase activity
decreased urocanic acid in stratum corneum

NeurologicBehavioralPsychiatricManifestations:
behavioral disorders (rare)

NeurologicCentralNervousSystem:
mental retardation (rare less than 1% of cases)
speech disorders (rare)

LaboratoryAbnormalities:
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:

31
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 very rare (1%) HP:0001249
2 neurological speech impairment 31 occasional (7.5%) HP:0002167
3 behavioral abnormality 31 occasional (7.5%) HP:0000708
4 histidinuria 31 HP:0002927
5 hyperhistidinemia 31 HP:0010906

MGI Mouse Phenotypes related to Histidinemia:

43
# 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 28 HAL

Anatomical Context for Histidinemia

MalaCards organs/tissues related to Histidinemia:

38
Skin, Testes

Publications for Histidinemia

Articles related to Histidinemia:

(show top 50) (show all 79)
# 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
Pharmacokinetics of stable isotopically labeled L-histidine in humans and the assessment of in vivo histidine ammonia lyase activities. ( 8825190 )
1996
9
On the nature of the irreversible inhibition of histidine ammonia lyase by cysteine and dioxygen. ( 8831970 )
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
Histidinemia: a biochemical variant or a disease? ( 8463510 )
1993
14
Inactivation of histidine ammonia-lyase from Streptomyces griseus by dicarbonyl reagents. ( 8507666 )
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
Characterization of L-histidine ammonia-lyase immobilized by microencapsulation in artificial cells: preparation, kinetics, stability, and in vitro depletion of histidine. ( 2347667 )
1990
19
Biochemical investigation of histidinemia in schizophrenic patients. ( 2297554 )
1990
20
Joubert's syndrome associated with congenital ocular fibrosis and histidinemia. ( 2469414 )
1989
21
Hyperhistaminemia in patients with histidinemia due to increased decarboxylation of histidine. ( 2482142 )
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
Genetic heterogeneity of histidinemia detected by screening newborn infants in Japan. ( 3836313 )
1985
25
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
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
Skin histidase activity and urine formiminoglutamic acid (FIGLU) in patients with histidinemia found by screening newborn infants. ( 7067128 )
1982
30
Histidinemia: biochemical parameters for diagnosis. ( 7211776 )
1981
31
Histidinemia: biochemistry and behavior. ( 7211773 )
1981
32
Relationship between skin histidase activity and blood histidine response to histidine intake in patients with histidinemia. ( 7400897 )
1980
33
Serotonin in experimental histidinemia. ( 7464987 )
1980
34
A new sensitive method for assay of histidase in human skin and detection of heterozygotes for histidinemia. ( 476954 )
1979
35
The nutritional therapy of histidinemia. ( 490237 )
1979
36
Histidinemia and infantile autism. ( 438113 )
1979
37
Sibship with histidinemia and an unrelated encephalopathy. Clinical and biochemical studies. ( 617985 )
1977
38
Deficits in discrimination and maze learning resulting from maternal histidinemia in rats. ( 563880 )
1977
39
Studies on the production and assessment of experimental histidinemia in the rat. ( 8133 )
1976
40
Histidinemia. Classical and atypical form in siblings. ( 1146783 )
1975
41
Infantile spasms associated with histidinemia. ( 1167649 )
1975
42
Histidinemia with features of the Marfan syndrome. ( 1127531 )
1975
43
Histidinemia produced in the rat by treatment with nitromethane1. ( 1178145 )
1975
44
Histidinemia. Report of a case. ( 4443038 )
1974
45
Histidinemia and "normohistidinemic histidinuria". Report of three cases and the effect of different protein intakes on urinary excretion of histidine. ( 4820585 )
1974
46
Histidinemia. ( 4453360 )
1974
47
Routine newborn screening for histidinemia. Clinical and biochemical results. ( 4421298 )
1974
48
Dietary correction of histidinemia in older children possible. ( 4776480 )
1973
49
The use of histidase for the study of amniotic cell origin and histidinemia. ( 4126443 )
1973
50
Application of automation and systems analysis to detection of histidinemia. ( 4561695 )
1972

Variations for Histidinemia

UniProtKB/Swiss-Prot genetic disease variations for Histidinemia:

71
# 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

Expression for Histidinemia

Search GEO for disease gene expression data for Histidinemia.

Pathways for Histidinemia

Pathways related to Histidinemia according to KEGG:

36
# 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 12)
# Name GO ID Score Top Affiliating Genes
1 cellular amino acid biosynthetic process GO:0008652 9.63 CTH GOT1 GOT2
2 2-oxoglutarate metabolic process GO:0006103 9.51 GOT1 GOT2
3 oxaloacetate metabolic process GO:0006107 9.49 GOT1 GOT2
4 aspartate metabolic process GO:0006531 9.48 GOT1 GOT2
5 dicarboxylic acid metabolic process GO:0043648 9.43 GOT1 GOT2
6 cysteine biosynthetic process GO:0019344 9.4 CTH GGT1
7 aspartate catabolic process GO:0006533 9.37 GOT1 GOT2
8 aspartate biosynthetic process GO:0006532 9.32 GOT1 GOT2
9 glutamate catabolic process to aspartate GO:0019550 9.26 GOT1 GOT2
10 glutamate catabolic process to 2-oxoglutarate GO:0019551 9.16 GOT1 GOT2
11 glutamate metabolic process GO:0006536 9.13 GGT1 GOT1 GOT2
12 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 9.54 ADSL CTH HAL
2 pyridoxal phosphate binding GO:0030170 9.33 CTH GOT1 GOT2
3 transaminase activity GO:0008483 9.32 GOT1 GOT2
4 carboxylic acid binding GO:0031406 9.26 GOT1 GOT2
5 L-aspartate:2-oxoglutarate aminotransferase activity GO:0004069 8.96 GOT1 GOT2
6 L-phenylalanine:2-oxoglutarate aminotransferase activity GO:0080130 8.62 GOT1 GOT2

Sources for Histidinemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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