MCID: HRT031
MIFTS: 48

Hartnup Disorder

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

Aliases & Classifications for Hartnup Disorder

MalaCards integrated aliases for Hartnup Disorder:

Name: Hartnup Disorder 53 49 24 55 71 36 13
Hartnup Disease 53 37 12 72 49 24 55 41 14 69
Hnd 53 49 71
Neutral 1 Amino Acid Transport Defect 12 28
Neutral Amino Acid Transport Defect 12 24
Deficiency of Tryptophan Oxygenase 12
Aminoaciduria, Hartnup Type 55
Tryptophan Oxygenase 13
Hartnup's Disease 24

Characteristics:

Orphanet epidemiological data:

55
hartnup disease
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Worldwide),1-9/100000 (United States); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
hartnup disorder:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hartnup Disorder

NIH Rare Diseases : 49 Hartnup disease is a metabolic disorder characterized by abnormal transport of certain amino acids in the kidney and gastrointestinal system. It is a type of aminoaciduria. The condition may be diagnosed based on the results of newborn screening tests. Most people with the condition have no symptoms (asymptomatic). For those who do show symptoms, the onset of the disease is usually between the ages of 3 and 9; occasionally the disease may present in adulthood. Mental development is usually normal, though a few cases with intellectual impairment have been reported. The signs and symptoms of Hartnup disease incude skin photosensitivity, neurologic findings, psychiatric symptoms, and ocular (eye) findings. Hartnup disease is caused by mutations in the SLC6A19 gene and is inherited in an autosomal recessive manner. People with Hartnup disease may benefit from a high-protein diet, protection from sunlight, vitamin supplementation, and avoidance of certain drugs/medications. In some cases, treatment with nicotinamide supplements and tryptophan ethyl ester may be indicated. Last updated: 12/17/2015

MalaCards based summary : Hartnup Disorder, also known as hartnup disease, is related to cystinuria and hyper ige syndrome, and has symptoms including ataxia, seizures and photophobia. An important gene associated with Hartnup Disorder is SLC6A19 (Solute Carrier Family 6 Member 19), and among its related pathways/superpathways are Protein digestion and absorption and Mineral absorption. Affiliated tissues include Kidney, skin and eye, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

UniProtKB/Swiss-Prot : 71 Hartnup disorder: Autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport noted for its clinical variability. First described in 1956, HND is characterized by increases in the urinary and intestinal excretion of neutral amino acids. Individuals with typical Hartnup aminoaciduria may be asymptomatic, some develop a photosensitive pellagra-like rash, attacks of cerebellar ataxia and other neurological or psychiatric features. Although the definition of HND was originally based on clinical and biochemical abnormalities, its marked clinical heterogeneity has led to it being known as a disorder with a consistent pathognomonic neutral hyperaminoaciduria.

Genetics Home Reference : 24 Hartnup disease is a condition caused by the body's inability to absorb certain protein building blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino acids to produce other substances, such as vitamins and proteins. Most people with Hartnup disease are able to get the vitamins and other substances they need with a well-balanced diet.

Disease Ontology : 12 An amino acid metabolic disorder that is caused by abnormalities of the renal tubules and is characterized especially by aminoaciduria involving only monocarboxylic monoamines, a dry red scaly rash, and episodic muscular incoordination due to the effects of the disease on the cerebellum.

Wikipedia : 72 Hartnup disease (also known as \"pellagra-like dermatosis\" and \"Hartnup disorder\") is an autosomal... more...

Description from OMIM: 234500

Related Diseases for Hartnup Disorder

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

(show all 15)
# Related Disease Score Top Affiliating Genes
1 cystinuria 29.4 SLC1A4 SLC6A18
2 hyper ige syndrome 11.0
3 hydrops, lactic acidosis, and sideroblastic anemia 9.8
4 acrodermatitis enteropathica, zinc-deficiency type 9.8
5 celiac disease 1 9.8
6 arteriovenous fistula 9.8
7 diarrhea 9.8
8 kwashiorkor 9.8
9 acrodermatitis 9.8
10 dermatitis 9.8
11 dystonia 9.8
12 enteropathica 9.8
13 hydroa vacciniforme 9.8
14 hyperglycinuria 9.3 SLC6A18 SLC6A19 SLC6A20
15 iminoglycinuria 9.2 SLC6A18 SLC6A19 SLC6A20

Graphical network of the top 20 diseases related to Hartnup Disorder:



Diseases related to Hartnup Disorder

Symptoms & Phenotypes for Hartnup Disorder

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
hypertonia
intermittent cerebellar ataxia
delayed cognitive development

Laboratory Abnormalities:
neutral hyperaminoaciduria

Skin Nails Hair Skin:
light-sensitive dermatitis

Neurologic Peripheral Nervous System:
increased deep tendon reflexes

Neurologic Behavioral Psychiatric Manifestations:
psychosis
emotional instability

Growth Height:
short stature (in some patients)

Head And Neck Mouth:
atrophic glossitis (rare)


Clinical features from OMIM:

234500

Human phenotypes related to Hartnup Disorder:

55 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0001250
3 photophobia 55 31 frequent (33%) Frequent (79-30%) HP:0000613
4 nystagmus 55 31 frequent (33%) Frequent (79-30%) HP:0000639
5 emotional lability 55 31 hallmark (90%) Very frequent (99-80%) HP:0000712
6 intellectual disability 55 31 occasional (7.5%) Occasional (29-5%) HP:0001249
7 muscular hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001252
8 hyperreflexia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001347
9 eeg abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0002353
10 encephalitis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002383
11 hallucinations 55 31 hallmark (90%) Very frequent (99-80%) HP:0000738
12 global developmental delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001263
13 malabsorption 55 31 frequent (33%) Frequent (79-30%) HP:0002024
14 short stature 55 31 occasional (7.5%) Occasional (29-5%) HP:0004322
15 abnormal blistering of the skin 55 31 occasional (7.5%) Occasional (29-5%) HP:0008066
16 strabismus 55 31 frequent (33%) Frequent (79-30%) HP:0000486
17 anxiety 55 31 hallmark (90%) Very frequent (99-80%) HP:0000739
18 hypopigmented skin patches 55 31 occasional (7.5%) Occasional (29-5%) HP:0001053
19 migraine 55 31 hallmark (90%) Very frequent (99-80%) HP:0002076
20 irregular hyperpigmentation 55 31 occasional (7.5%) Occasional (29-5%) HP:0007400
21 gingivitis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000230
22 skin rash 55 31 frequent (33%) Frequent (79-30%) HP:0000988
23 cutaneous photosensitivity 55 31 hallmark (90%) Very frequent (99-80%) HP:0000992
24 glossitis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000206
25 neutral hyperaminoaciduria 55 31 hallmark (90%) Very frequent (99-80%) HP:0008353
26 abnormal urinary color 55 31 hallmark (90%) Very frequent (99-80%) HP:0012086
27 hypertonia 31 HP:0001276
28 abnormality of the eye 55 Frequent (79-30%)
29 abnormality of vision 55 Frequent (79-30%)
30 psychosis 31 HP:0000709
31 episodic ataxia 31 HP:0002131

UMLS symptoms related to Hartnup Disorder:


seizures

GenomeRNAi Phenotypes related to Hartnup Disorder according to GeneCards Suite gene sharing:

25 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.47 SLC6A20
2 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.47 SLC6A18 SLC6A20
3 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.47 SLC6A18
4 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.47 SLC6A18
5 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.47 SLC6A20
6 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.47 SLC6A18
7 Increased shRNA abundance (Z-score > 2) GR00366-A-189 9.47 SLC6A20
8 Increased shRNA abundance (Z-score > 2) GR00366-A-2 9.47 SLC6A18
9 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.47 SLC6A20
10 Increased shRNA abundance (Z-score > 2) GR00366-A-35 9.47 SLC6A18
11 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.47 SLC6A18
12 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.47 SLC6A18
13 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.47 SLC6A20

Drugs & Therapeutics for Hartnup Disorder

Search Clinical Trials , NIH Clinical Center for Hartnup Disorder

Cochrane evidence based reviews: hartnup disease

Genetic Tests for Hartnup Disorder

Genetic tests related to Hartnup Disorder:

# Genetic test Affiliating Genes
1 Neutral 1 Amino Acid Transport Defect 28 SLC6A19

Anatomical Context for Hartnup Disorder

MalaCards organs/tissues related to Hartnup Disorder:

38
Skin, Eye, Kidney, Testes, Cerebellum
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Hartnup Disorder:
# Tissue Anatomical CompartmentCell Relevance
1 Kidney Proximal Tubule Proximal Tubule Cells Potential therapeutic candidate, affected by disease

Publications for Hartnup Disorder

Articles related to Hartnup Disorder:

(show top 50) (show all 77)
# Title Authors Year
1
Severe persistent unremitting dermatitis, chronic diarrhea and hypoalbuminemia in a child; Hartnup disease in setting of celiac disease. ( 25526748 )
2014
2
Hartnup disease masked by kwashiorkor. ( 20824986 )
2010
3
Novel mutation in SLC6A19 causing late-onset seizures in Hartnup disorder. ( 20399395 )
2010
4
A novel missense mutation in the SLC6A19 gene in a Chinese family with Hartnup disorder. ( 19335424 )
2009
5
The role of the neutral amino acid transporter B0AT1 (SLC6A19) in Hartnup disorder and protein nutrition. ( 19472175 )
2009
6
A protein complex in the brush-border membrane explains a Hartnup disorder allele. ( 18424768 )
2008
7
Hartnup disease. ( 19967017 )
2008
8
Further evidence for allelic heterogeneity in Hartnup disorder. ( 18484095 )
2008
9
Acrodermatitis enteropathica-like eruptions in a child with Hartnup disease. ( 16780476 )
2006
10
Neutral amino acid transport in epithelial cells and its malfunction in Hartnup disorder. ( 15667315 )
2005
11
Hartnup disorder: unraveling the mystery. ( 15681018 )
2005
12
Spontaneous scalp arteriovenous fistula in a child with hartnup disease. ( 15174904 )
2004
13
Molecular cloning of mouse amino acid transport system B0, a neutral amino acid transporter related to Hartnup disorder. ( 15044460 )
2004
14
Mutations in SLC6A19, encoding B(0)AT1, cause Hartnup disorder. ( 15286787 )
2004
15
Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. ( 15286788 )
2004
16
A clinicobiochemical study of tryptophan and other plasma and urinary amino acids in the family with Hartnup disease. ( 15206746 )
2003
17
Hartnup disorder: polymorphisms identified in the neutral amino acid transporter SLC1A5. ( 12555937 )
2002
18
Homozygosity mapping to chromosome 5p15 of a gene responsible for Hartnup disorder. ( 11394870 )
2001
19
A candidate mouse model for Hartnup disorder deficient in neutral amino acid transport. ( 9060408 )
1997
20
Hartnup disease presenting in an adult. ( 7955499 )
1994
21
Hartnup disease. ( 8125700 )
1993
22
Hartnup disease: MR findings. ( 1950900 )
1991
23
Tryptophan and its metabolites in a family with Hartnup disease. ( 1722956 )
1991
24
Use of ethyl esters of tryptophan to bypass the absorption defect in Hartnup disease. ( 2336209 )
1990
25
Intermittent dystonia in Hartnup disease. ( 2712944 )
1989
26
Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester. ( 2472426 )
1989
27
Maternal Hartnup disorder. ( 3728570 )
1986
28
Julius Caesar and the Julian emperors. A family cluster with Hartnup disease? ( 3532855 )
1986
29
Occurrences of methylmalonic aciduria and Hartnup disorder in the same family. ( 6478642 )
1984
30
Treatment of Hartnup disease with nicotinic acid. ( 6236384 )
1984
31
Hartnup disease (a case report). ( 7461844 )
1980
32
Hartnup disease--a case report. ( 751957 )
1978
33
Note on Hartnup disease. ( 735931 )
1978
34
Hartnup disease in New South Wales. ( 909480 )
1977
35
Natural history of Hartnup disease. ( 836052 )
1977
36
A case of Hartnup disorder with hypoalbuminemia and edema. ( 618038 )
1977
37
Intestinal absorption of amino acids and peptides in Hartnup disorder. ( 1272631 )
1976
38
Proceedings: Absorption of amino acids and peptides in Hartnup disease. ( 4817256 )
1974
39
Hartnup disease. A report on two siblings. ( 4761306 )
1973
40
Absorption of amino acids and peptides in a child with a variant of Hartnup disease and coexistent coeliac disease. ( 5086513 )
1972
41
Transport of dibasic amino acids, cystine, and tryptophan by cultured human fibroblasts: absence of a defect in cystinuria and Hartnup disease. ( 5054467 )
1972
42
Studies of intestinal transport defect in Hartnup disease. ( 5157127 )
1971
43
Hartnup disease. ( 5141735 )
1971
44
Hartnup disease. A case report. ( 5532073 )
1970
45
Intestinal absorption of two dipeptides in Hartnup disease. ( 5428040 )
1970
46
Intestinal absorption of dipeptides and corresponding free amino acids in Hartnup disease. ( 5448166 )
1970
47
Intestinal absorption and biopsy transport of peptides and amino acids in Hartnup disease. ( 5493936 )
1970
48
Studies on intestinal absorption of amino acids and a dipeptide in a case of Hartnup disease. ( 4246731 )
1970
49
Hartnup disease. ( 4237364 )
1969
50
Cellular transport of L-histidine in Hartnup disease. ( 5796364 )
1969

Variations for Hartnup Disorder

UniProtKB/Swiss-Prot genetic disease variations for Hartnup Disorder:

71
# Symbol AA change Variation ID SNP ID
1 SLC6A19 p.Arg57Cys VAR_023314 rs762989809
2 SLC6A19 p.Asp173Asn VAR_023315 rs121434346
3 SLC6A19 p.Leu242Pro VAR_023317 rs200745023
4 SLC6A19 p.Glu501Lys VAR_023319

ClinVar genetic disease variations for Hartnup Disorder:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC6A19 SLC6A19, IVS8, T-G, +2 single nucleotide variant Pathogenic
2 SLC6A19 SLC6A19, 2-BP DEL, 884-885TG deletion Pathogenic
3 SLC6A19 NM_001003841.2(SLC6A19): c.517G> A (p.Asp173Asn) single nucleotide variant Pathogenic/Likely pathogenic rs121434346 GRCh37 Chromosome 5, 1212453: 1212453
4 SLC6A19 NM_001003841.2(SLC6A19): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs121434347 GRCh37 Chromosome 5, 1213632: 1213632

Expression for Hartnup Disorder

Search GEO for disease gene expression data for Hartnup Disorder.

Pathways for Hartnup Disorder

Pathways related to Hartnup Disorder according to KEGG:

36
# Name Kegg Source Accession
1 Protein digestion and absorption hsa04974
2 Mineral absorption hsa04978

GO Terms for Hartnup Disorder

Cellular components related to Hartnup Disorder according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.63 ACE2 RNF186 SLC1A4 SLC6A18 SLC6A19 SLC6A20
2 integral component of plasma membrane GO:0005887 9.26 SLC1A4 SLC6A18 SLC6A19 SLC6A20
3 brush border membrane GO:0031526 8.62 SLC6A18 SLC6A19

Biological processes related to Hartnup Disorder according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.71 SLC1A4 SLC6A18 SLC6A19 SLC6A20
2 transmembrane transport GO:0055085 9.62 SLC1A4 SLC6A18 SLC6A19 SLC6A20
3 amino acid transmembrane transport GO:0003333 9.37 SLC6A18 SLC6A19
4 proline transport GO:0015824 9.26 SLC1A4 SLC6A20
5 proline transmembrane transport GO:0035524 9.16 SLC1A4 SLC6A20
6 neurotransmitter transport GO:0006836 9.13 SLC6A18 SLC6A19 SLC6A20
7 amino acid transport GO:0006865 8.92 SLC1A4 SLC6A18 SLC6A19 SLC6A20

Molecular functions related to Hartnup Disorder according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 symporter activity GO:0015293 9.46 SLC1A4 SLC6A18 SLC6A19 SLC6A20
2 neutral amino acid transmembrane transporter activity GO:0015175 9.32 SLC1A4 SLC6A19
3 L-proline transmembrane transporter activity GO:0015193 9.26 SLC1A4 SLC6A20
4 neurotransmitter:sodium symporter activity GO:0005328 9.13 SLC6A18 SLC6A19 SLC6A20
5 amino acid transmembrane transporter activity GO:0015171 8.92 SLC1A4 SLC6A18 SLC6A19 SLC6A20

Sources for Hartnup Disorder

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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