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Neutral 1 amino acid transport defect(HND)

MedGen UID:
6723
Concept ID:
C0018609
Disease or Syndrome
Synonyms: Hartnup disease; Hartnup disorder; HND
SNOMED CT: Neutral amino acid transport defect (80902009); Neutral 1 amino acid transport defect (80902009); Hartnup disease (80902009); Hartnup disorder (80902009); Deficiency of tryptophan pyrrolase (124208000); Deficiency of tryptophan oxygenase (124208000); Deficiency of tryptophan 2,3-dioxygenase (124208000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SLC6A19 (5p15.33)
 
Monarch Initiative: MONDO:0009324
OMIM®: 234500
Orphanet: ORPHA2116

Definition

Hartnup disorder (HND) is characterized by transient manifestations of pellagra, cerebellar ataxia, and psychosis. It is caused by impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa (summary by Kleta et al., 2004). [from OMIM]

Additional description

From MedlinePlus Genetics
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.

People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria). For most affected individuals, this is the only sign of the condition. However, some people with Hartnup disease have episodes during which they exhibit other signs, which can include skin rashes; difficulty coordinating movements (cerebellar ataxia); and psychiatric symptoms, such as depression or psychosis. These episodes are typically temporary and are often triggered by illness, stress, nutrient-poor diet, or fever. These features tend to go away once the trigger is remedied, although the aminoaciduria remains. In affected individuals, signs and symptoms most commonly occur in childhood.  https://medlineplus.gov/genetics/condition/hartnup-disease

Clinical features

From HPO
Neutral hyperaminoaciduria
MedGen UID:
344676
Concept ID:
C1856194
Finding
The presence of an abnormally increased concentration of neutral amino acids in the urine. The neutral amino acids are tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine and valine.
Elevated urinary indoleacetic acid level
MedGen UID:
1052629
Concept ID:
CN377141
Finding
The amount of indoleacetic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.
Hereditary episodic ataxia
MedGen UID:
314033
Concept ID:
C1720189
Disease or Syndrome
Periodic spells of incoordination and imbalance, that is, episodes of ataxia typically lasting from 10 minutes to several hours or days.
Generalized tonic seizure
MedGen UID:
322935
Concept ID:
C1836508
Disease or Syndrome
A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Glossitis
MedGen UID:
6618
Concept ID:
C0017675
Disease or Syndrome
Inflammation of the tongue.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeutral 1 amino acid transport defect
Follow this link to review classifications for Neutral 1 amino acid transport defect in Orphanet.

Professional guidelines

PubMed

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Recent clinical studies

Etiology

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
Wang X, Kulkarni D, Dozier M, Hartnup K, Paget J, Campbell H, Nair H; Usher Network for COVID-19 Evidence Reviews (UNCOVER) group
J Glob Health 2020 Dec;10(2):021102. doi: 10.7189/jogh.10.021102. PMID: 33312512Free PMC Article
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Diagnosis

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
Winchester S, Singh PK, Mikati MA
Handb Clin Neurol 2013;112:1213-7. doi: 10.1016/B978-0-444-52910-7.00043-X. PMID: 23622331
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DesGroseilliers JP, Shiffman NJ
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Therapy

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
Prabhu D, Dawe RS, Mponda K
Photodermatol Photoimmunol Photomed 2021 Mar;37(2):99-104. Epub 2021 Feb 2 doi: 10.1111/phpp.12659. PMID: 33471377
Nisoli E, Cinti S, Valerio A
Eat Weight Disord 2021 Jun;26(5):1647-1651. Epub 2020 Jul 20 doi: 10.1007/s40519-020-00963-y. PMID: 32691334Free PMC Article
Kahn G
Dermatol Clin 1986 Jan;4(1):107-16. PMID: 3521976
DesGroseilliers JP, Shiffman NJ
Can Med Assoc J 1976 Oct 23;115(8):768-70. PMID: 974966Free PMC Article

Prognosis

Winchester S, Singh PK, Mikati MA
Handb Clin Neurol 2013;112:1213-7. doi: 10.1016/B978-0-444-52910-7.00043-X. PMID: 23622331
Bröer S, Cavanaugh JA, Rasko JE
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Clinical prediction guides

Wang X, Li XY, Piao Y, Yuan G, Lin Y, Chen H, Wang Z, Li C, Wang C
Am J Med Genet A 2022 Jan;188(1):237-242. Epub 2021 Aug 30 doi: 10.1002/ajmg.a.62475. PMID: 34459558
Lukiw WJ, Pogue A, Hill JM
Cell Mol Neurobiol 2022 Jan;42(1):217-224. Epub 2020 Aug 25 doi: 10.1007/s10571-020-00947-7. PMID: 32840758Free PMC Article
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Microbes Infect 2013 Nov;15(13):866-73. Epub 2013 Aug 17 doi: 10.1016/j.micinf.2013.08.003. PMID: 23962453Free PMC Article
Bröer A, Juelich T, Vanslambrouck JM, Tietze N, Solomon PS, Holst J, Bailey CG, Rasko JE, Bröer S
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Bröer S, Cavanaugh JA, Rasko JE
Biochem Soc Trans 2005 Feb;33(Pt 1):233-6. doi: 10.1042/BST0330233. PMID: 15667315

Recent systematic reviews

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article

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