What are the other Names for this Condition? (Also known as/Synonyms)

• Hartnup Disorder
• HND (Hartnup Disease)

What is Hartnup Disease? (Definition/Background Information)

• 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 include 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

(Source: Hartnup Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hartnup Disease? (Age and Sex Distribution)

• Hartnup Disease is a rare congenital disorder. The presentation of symptoms may occur at birth
• However, in many asymptomatic children, the symptoms are seen when the child is between 3-9 years old. In rare cases, symptoms are observed into adulthood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hartnup Disease? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hartnup Disease is an inherited condition
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hartnup Disease? (Etiology)

• Hartnup Disease is caused by mutations in the SLC6A19 gene
• It is inherited in an autosomal recessive manner

(Source: Hartnup Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Hartnup Disease?

The signs and symptoms of Hartnup Disease may vary and include the following:

• Skin findings: Sensitivity to sunlight
• Neurologic symptoms: Ataxia, spasticity, headaches, and hypotonia
• Psychiatric symptoms: Anxiety, emotional instability, mood changes
• Ocular findings: Double vision, nystagmus, strabismus, photophobia
• Episodic ataxia
• Hypertonia
• Psychosis

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Abnormal urinary color
• Anxiety
• Ataxia
• Cutaneous photosensitivity
• EEG abnormality
• Emotional lability
• Hallucinations
• Hyperreflexia
• Migraine
• Muscular hypotonia
• Neutral hyperaminoaciduria

Frequently present symptoms in 30-79% of the cases:

• Malabsorption 
• Nystagmus
• Photophobia
• Skin rash 
• Strabismus

Occasionally present symptoms in 5-29% of the cases:

• Abnormal blistering of the skin 
• Encephalitis 
• Gingivitis
• Glossitis
• Hypopigmented skin patches 
• Intellectual disability
• Irregular hyperpigmentation 
• Seizures

(Source: Hartnup Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hartnup Disease Diagnosed?

Hartnup Disease is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies including prenatal tests
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hartnup Disease?

The complications of Hartnup Disease may include:

• Intellectual deficit
• Vision abnormalities
• Emotional and psychological stress

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hartnup Disease Treated?

• 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

(Source: Hartnup Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Hartnup Disease be Prevented?

Currently, Hartnup Disease may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hartnup Disease? (Outcomes/Resolutions)

• The prognosis of Hartnup Disease is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hartnup Disease:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/