Hartnup disease got its name after the Hartnup family was first discovered. Approximately 1 out of every 24,000 people have Hartnup illness in the world. I wrote this research article for a master’s nutrition course and will discuss the disease’s symptoms, biochemical pathway, treatment, and nutritional implications of Hartnup disease.
What is Hartnup Disease?
Hartnup is an autosomal recessive disease. The cause is a defective amino acid transporter. Autosomal recessive diseases are diseases in which 2 copies from 2 carriers of a mutated (changed) gene must be present. This means that each parent needs to pass down the SLC6A19 gene containing a mutation.
The amino acid transporter, B°AT1, is encoded by the SLC6A19 gene. Basically, the amino acid transporter is impaired if there is a mutation in the SLC6A19 gene. This specific transporter is responsible for reabsorbing neutral amino acids in the kidneys and intestines. Amino acids are the building blocks of protein. There are a total of 22 amino acids in the human body. When the body isn’t reabsorbing the amino acids, they are excreted in the kidneys. Without these amino acids to build protein, the person will experience various symptoms similar to Pellagra.
When is Hartnup Typically Diagnosed?
Children are born with no symptoms. Therefore, it is difficult to know if someone has the condition. Children may start to develop symptoms as they grow. This is due to the to the increase in protein needs as a child grows and develops.
What are the Symptoms of Hartnup Disease?
Environment and genes affect the symptoms in each individual. Some people have the disease but do not display any symptoms. Those following a western diet high in protein are more likely not to experience symptoms. However, for people with symptoms, life can be extremely stressful.
Symptoms often include:
Dermatitis may show as intermittent red, scaly rashes over the face, neck, hands, and legs. Advanced symptoms are delirium and diarrhea. Delirium occurs when a person has an episodic personality disorder. The characteristics of delirium are emotional instability, uncontrolled temper, and confusional-hallucinatory psychosis. Another common symptom is ataxia, with the person experiencing an unsteady gait, tremors, and dysarthria.
Symptoms are often episodic, lasting around two weeks. Often symptoms triggers are:
- sunlight exposure
- emotional stress
- sulfonamide drugs
Once the symptoms happen and a few weeks pass, patients can return to everyday life. Frequency of the attacks slows down after childhood. However, a person may suffer growth delays and developmental problems if Hartnup Disease is not treated in childhood.
Can a Person Die from Hartnup Disease?
Death is rare with Hartnup. However, death can occur with complications from the disease.
In one case, an 11-month-year-old girl came to the hospital with multiple complications. She had severe kwashiorkor (severe malnutrition), acrodermatitis enteropathy, diarrhea, and a UTI. The infant had been exclusively breastfeeding. She also had little intake of solid food.
Because Hartnup Disease is rare, doctors thought her complications were from kwashiorkor. The treatment focused treating the kwashiorkor. Therapy was gradual refeeding and supplements of vitamin d and calcium.
With treatment, the little girl took a turn for the worse. She now had edema (excess fluid in the body tissues). Additionally, she was developing severe skin eruptions in her perineal area. Then pneumonia came. The infant died after seven days in the hospital.
After her death, the laboratory analyzed her urinary amino acids. Her diagnosis was Hartnup Disease. Since she was so young and not eating solids, her protein intake was low. In an infant without Hartnup, the protein from breastmilk is sufficient at the age of 11 months. However, since the infant had Hartnup disease, the amino acids to build protein were excreted through urine. The result was severe malnutrition.
The previous case study is the only known death from Hartnup Disease.
What is the Biochemical Pathway of Hartnup Disease?
The cause of Hartnup disease is due to a mutation in the SLC6A19. The SLC6A19 is mapped to the chromosome 5p15. Other phenotypes of the chromosome include hyperglycinemia (abnormality of the renal transport of glycine) and iminoglycinuria eugenic.
At the core of Hartnup disease, to understand the biochemical pathway, one must understand the absorption process of amino acids. In healthy people, the reabsorption and filtering of amino acids happens correctly in the kidneys. The proximal tubules in the kidney are the primary site for reabsorption of amino acids. This is a very important process. The reabsorption allows the body to create proteins from the amino acids. If the amino acids are not reabsorbed and get excreted in urine, then the creation of a complete protein does not happen. The SLC6A19 gene helps facilitates this process.
Of all of the 22 amino acids, Tryptophan is the least plentiful. Tryptophan come from food. It is a precursor to serotonin, a vital neurotransmitter. Serotonin is responsible for regulating sleep, appetite, sexuality, mood, and metabolism. There is a relationship between the levels of serotonin in the brain and Tryptophan in the blood. Tryptophan is critical for the creation of the vitamin, Niacin. Hence, why symptoms of Pellagra often develop in those with Hartnup disease. If someone has Pellagra, but does not have niacin deficiency, a screening for Hartnup disease should occur.
What is the Treatment for Hartnup Disease?
There is no cure currently for Hartnup. However, control of the disease happens through diet and supplementation. Many people with Hartnup are asymptomatic, especially from countries with protein-rich diets. People from rural China, for instance, primary have a high carbohydrate, low protein diet. In this region, symptoms tend to occur more for those with Hartnup disease. It is thought that when one eats adequate protein, the symptoms are kept more at bay.
People with Hartnup disease should consume a diet high in protein. Additionally, a daily nicotinamide supplement of 50-250mg should be taken. Those with the disease should also avoid sunlight and sulfonamide drugs.
If symptoms persist, working with your doctor and registered dietitian on increasing dietary protein.