Hartnup disease is a rare and autosomal recessive metabolic disorder that blocks the transport of amino acids across cell membranes by an allelic mutation. The disease is extremely variable and can affect the skin, kidneys, liver, but also the central nervous system.
What is Hartnup disease?
In medicine, Hartnup disease or Hartnup syndrome is a metabolic disorder that affects the transport of amino acids through the cell membranes. It is an inherited disease that is passed on in an autosomal recessive manner. This means that both homologous chromosomes must carry the defective allele for the disease to break out. Therefore, Hartnup’s disease is rather rare.
Not all carriers of the gene develop symptoms at all. Because up to six different gene variants are affected by the disease, the metabolic disorder is extremely variable. The disease can express itself, for example, exclusively in a transport difficulty of amino acids in the kidneys, but also exclusively affect the intestines.
The disease is often compared to what is known as pellagra, a hypovitaminosis caused by malnutrition that causes similar symptoms. The disease was first documented in 1956 in children of the London Hartnup family. Today, experts assume that Julius Caesar already suffered from the metabolic disorder.
The cause of Hartnup syndrome is a gene mutation. In this context, medicine assumes a total of 21 different mutations of SLC6A19 in chromosome five gene locus p15.33, each of which has different effects on the transport of amino acids in the body.
As a rule, patients with Hartnup syndrome suffer from two different mutations, with the majority of them carrying the D173N allele as a gene carrier. Mutations in the alleles D173N or P265L have transport channels that are directly dependent on ACE2 in the gut or Tmem27 in the kidneys.
The genetic defect causes a lack of certain membrane proteins in the body, which appear as neutral amino acid transporters in healthy people. These amino acid transporters smuggle both neutral and aromatic amino acids through the body cells. The effects of the gene defect appear most clearly in body tissues with increased amino acid uptake, although they are in principle not limited to these tissues.
Symptoms, Ailments & Signs
Depending on the severity, Hartnup’s disease manifests itself in a wide variety of symptoms and progresses in phases. In particular , fever, stress and medication can trigger a flare-up. Erythematous eczema, i.e. special skin lesions, appear on the skin during a flare-up. The gastrointestinal tract is affected by symptoms such as recurring or even persistent diarrhea.
Under certain circumstances, psychiatric disorders may also be accompanied by neurological symptoms, such as ataxia or paralysis, which usually resolve again. In most cases, the immune system in particular suffers permanent damage, so that those affected by Hartnup syndrome, for example, become ill more quickly.
That being said, hypersensitivity to insulin can be symptomatic of the condition. The same applies to anatomical damage to the adrenal glands or liver. Under certain circumstances, headaches and photosensitivity can also occur during a flare-up.
Diagnosis & History
Since Hartnup’s disease is variable, it is difficult to generalize about the course of the disease. Ultimately, the metabolic disorder primarily affects the upper small intestine and certain cells of the kidneys. The effects of Hartnup’s disease on the kidneys are mostly reduced absorption, i.e. an inability to keep amino acids in the bloodstream. The amino acids are lost because they accumulate in the urine instead of in the blood.
However, if the sufferer is getting enough protein, then this loss is of no consequence and does not cause any symptoms. However, since those affected by Hartnup’s disease often also have a resorption disorder in the small intestine, the losses are usually serious overall, because certain essential amino acids are simply necessary for survival and a healthy body obtains a large part of these vital substances in the intestine through amino acid recycling.
If left untreated, Hartnup syndrome often leads to serious damage and can even have fatal consequences. Nevertheless, medicine today generally assumes that the course of the disease will be benign, since suitable treatment methods are available to compensate for the loss of amino acids, even for severe cases of Harntup’s syndrome. The disease is relatively difficult to detect due to the many mutations.
Doctors usually order a urinalysis if the genetic defect is suspected, which may confirm the presence of amino acids in the urine and thus secure the first suspicion. If the first suspicion cannot be confirmed by the urine sample, the disease is not necessarily ruled out. In this case, a reliable diagnosis using blood values is difficult or even impossible.
Under certain circumstances, however, a test for porphyrogens can provide clues in which hydrochloric acid is added to the morning urine. If the urine is then heated, porphyrogens form a red color, which corresponds to a positive test result. However, this test is also rather unspecific.
Hartnup’s disease can affect a variety of internal organs in the body, causing discomfort or complications. In most cases, however, the liver, kidneys and skin are affected by Hartnup’s disease. Furthermore, it can also lead to restrictions and complaints in the central nervous system. The patient primarily suffers from stress and fever.
Diarrhea also occurs, which can often be accompanied by vomiting and severe nausea. The impairment of the central nervous system sometimes leads to paralysis or sensory disturbances in the patient. These can also lead to psychological problems and depression. The patient’s immune system is usually weakened by Hartnup’s disease, so that inflammation and various infections often develop.
Damage to the liver and kidneys occurs. In the worst case, the patient suffers from complete renal insufficiency and is therefore dependent on dialysis or a donor organ. The symptoms of Hartnup’s disease are treated with medication. There are no further complications. Psychological measures are also usually necessary.
When should you go to the doctor?
Unfortunately, the symptoms of Hartnup’s disease are not particularly specific, so no general prediction can be made about when to see a doctor. The symptoms often appear in flares, which can indicate the disease. This usually leads to severe diarrhea or other problems in the stomach and intestines. Skin problems can also indicate Hartnup’s disease and should be examined.
Furthermore, paralysis is a typical symptom of the disease, the severity of which can vary greatly. Those affected often also suffer from a weakened immune system and become ill relatively often or suffer from infections and inflammations.
In some cases, Hartnup’s disease can also lead to high sensitivity to insulin, which should also be investigated. The first examination can be carried out by a pediatrician or by a general practitioner. Since the disease cannot be completely cured and is only treated symptomatically, the general practitioner can usually also carry out this treatment.
Treatment & Therapy
Patients with Hartnup’s disease are usually treated with replacement therapy. This means that they are provided with a daily dietary supplement in the form of niacin. In the initial phase, they take up to three grams of the substance daily, with the dose being regulated at 500 milligrams per day in the maintenance phase. A particularly high-protein diet with lots of tryptophan supplements this therapy method.
Dairy products, poultry, potatoes and nuts are at the heart of the diet. If the disease progresses severely, these methods are not sufficient to compensate for the transport defect, so that intravenous substitutions with chemically modified amino acids must be used. Depending on which symptoms are caused by a flare-up, physiotherapeutic measures to combat the symptoms of paralysis may also be used in addition to ointments to combat the skin symptoms.
Outlook & Forecast
The outlook for Hartnup’s disease varies. They depend on the extent of the loss of neutral and essential amino acids. If only the kidneys are affected, diet can compensate for the loss. Hartnup disease is genetic. But she develops great variability.
Thus, several possible mutations are suspected. As a result, there is a wide spectrum of the disease, ranging from asymptomatic to the most severe symptoms. Most people affected do not develop any symptoms and can live a normal life expectancy without treatment.
However, the severe forms of Hartnup’s disease often lead to death if left untreated. Many organs of the body can be affected by the deterioration. Due to a lack of transport proteins, neutral and aromatic amino acids are transported through the cells only insufficiently or not at all. They are lost to the body through excretion in the urine.
In severe cases, amino acids from degraded body cells can no longer be used at all. This can go so far that essential and non-essential amino acids supplied through food are no longer sufficient to maintain vital functions. Many organs and organ systems such as the liver, pancreas, adrenal glands, skin, intestines, central nervous system or immune system are weakened.
In some cases, the administration of niacin can improve the transport problems. In particularly severe cases of Hartnup’s disease, the important amino acids must be substituted intravenously throughout life in order to increase life expectancy.
Hartnup’s disease cannot be prevented because the metabolic disease is an inherited genetic defect. However, with a prevalence of 1:24,000, the disease is relatively rare.
In the case of Hartnup’s disease, the patient has very few direct follow-up measures available. With this disease, however, early detection and treatment of the disease is very important to prevent further complications or symptoms. In the case of Hartnup’s disease, the person affected should consult a doctor as soon as the first symptoms and signs appear in order to prevent the symptoms from getting worse.
It cannot heal on its own. The treatment of this disease is therefore in most cases by taking various medications. The patient should always ensure that the dosage is correct and that it is taken regularly in order to alleviate the symptoms. In many cases, a change in diet is necessary, and a doctor can also draw up a nutrition plan.
Furthermore, some people with Hartnup’s disease are dependent on physiotherapy measures to treat the symptoms. Many exercises from such therapy can also be carried out at home. The loving care and support of those affected also has a positive effect on the course of this disease. Above all, depression or mental upsets can be prevented in this way.
You can do that yourself
Since Hartnup’s disease is an inherited defect, the disease cannot usually be prevented. Those affected are always dependent on treatment by a doctor. For this reason, there is no direct possibility of self-help in the case of the disease.
In most cases, those affected are dependent on substitution therapy to alleviate the symptoms. Care must be taken to ensure that it is taken regularly and in the correct dose. If in doubt, always consult a doctor.
Furthermore, a diet with tryptophan can also have a very good effect on Hartnup’s disease. For this reason, potatoes, poultry and dairy products are particularly suitable. Nuts are also an important part of this diet. Paralysis or sensory disturbances are usually treated therapeutically. These exercises can often be done at home to speed up the healing of Hartnup’s disease.
In the case of severe paralysis, however, those affected are dependent on loving support in their everyday lives. Contact with other people affected by the disease can possibly prevent psychological problems.