Diseases

Blue Diaper Syndrome – Causes, Symptoms & Treatment

Blue Diaper Syndrome

The blue diaper syndrome is an inherited metabolic disease with the main symptom tryptophan malabsorption. The lack of absorption through the intestine results in conversion and excretion via the kidneys, so that the urine turns blue. Treatment is intravenous tryptophan supplementation.

What is Blue Diaper Syndrome?

Blue diaper syndrome is also known as tryptophan malabsorption syndrome. This is an extremely rare metabolic disease that is one of the congenital metabolic disorders . Patients suffer from malabsorption of tryptophan. Tryptophan is an amino acid that cannot be absorbed through the intestinal wall into the bloodstream by patients with blue diaper syndrome.

The tryptophan remains in the intestines, where it is excreted via the kidneys after conversion processes. In contact with air, the substance turns blue. Hence the name of blue diaper syndrome. All other symptoms of the symptom complex symptoms are also due to tryptophan malabsorption and the lack of the substance in the blood.

In the case of the blue diaper syndrome, there is sometimes also talk of a familial hypercalcemia with the accompanying symptoms of nephrocalcinosis, hyperphosphaturia and indicanuria, which is caused by a disturbance in the absorption of tryptophan.

causes

Blue Diaper Syndrome is extremely rare and due to its rarity not fully researched. Nevertheless, the hereditary connections are now known. The exact inheritance of the disease is still unclear. An autosomal recessive and an X-linked recessive inheritance are under discussion. The molecular-biological cause of the syndrome is also still unknown.

There are many speculations about the cause, all of which assume a genetic mutation. Mutations of the L-type amino acid transporter 2, for example, can be considered for the disease. The genes coding for this are SLC7A8 and LAT2, which are located on chromosome 14 in gene locus q11.2.

Equally conceivable causes would be mutations of the T-type amino acid transporter 1 on gene SLC16A10 and gene TAT1. These genes are located on chromosome 6 in gene locus q21-q22. Whether external factors such as exposure to toxins play a role in the development of blue diaper syndrome is unknown.

Symptoms, Ailments & Signs

Blue diaper syndrome has all the symptoms of acquired tryptophan malabsorption. In addition to the lack of tryptophan in the blood, the patients suffer from severe hypercalcemia associated with nephrocalcinosis. Calcium salts are deposited in the kidney tissue of those affected, which can later lead to kidney failure if left untreated .

In addition, the hydrogen ion excretion of patients is higher than that of healthy people. The patients also excrete large amounts of phosphorus via the kidneys, so that one can speak of hyperphosphaturia. However, the most characteristic symptom of the disease is the blue discoloration of the diapers.

Because the gut does not absorb tryptophan, gut bacteria convert the amino acid to indole and its compounds. These substances are absorbed by the intestinal mucosa and migrate to the liver, where they are converted to indican. The indican is excreted renally through the urine and is responsible for the blue discoloration of the diapers.

Diagnose

The first suspected diagnosis of blue diaper syndrome hits the doctor based on visual diagnosis or anamnestic diagnosis as soon as the blue discoloration of the diapers is mentioned. Since acquired tryptophan malabsorption is also associated with the symptoms of blue diaper syndrome and no molecular genetic analysis is available for the hereditary form of such a metabolic disease, a corresponding suspected diagnosis can only be secured with difficulty.

So although blood tests can show a deficiency in the amino acid and hypercalcaemia, ultimately there can be no question of a reliable diagnosis until the responsible gene is identified. However, if several cases of blue diaper syndrome are observed in a family, the diagnosis can certainly be considered certain.

complications

Since the blue diaper syndrome is a congenital malabsorption of the amino acid tryptophan, it must be given to the affected children as soon as the disease is diagnosed. However, the patient’s intestines cannot absorb the amino acid, so direct administration into the blood is recommended. This form of therapy is unavoidable, because tryptophan is an important component of countless processes in the human body and is involved in the formation of the tissue hormone serotonin, among other things.

If tryptophan malabsorption is left untreated, there is a serious risk of hypercalcaemia and renal failure resulting from associated nephrocalcinosis . This can then necessitate dialysis or even a donor organ, which significantly reduces the quality of life of the young patients. Many of those affected also have damage to their eyes, which is why complications can also arise in the area of ​​ametropia.

Because it is still not clear what the cause of blue diaper syndrome is, there is no way to prevent this dangerous metabolic disorder . It is therefore imperative that parents contact the pediatrician immediately when they find the first blue-colored diapers, in order to spare the child worse consequences.

When should you go to the doctor?

If a blue discoloration of the diapers is noticed, the affected child should be taken to the pediatrician immediately . The doctor can then diagnose blue diaper syndrome visually and confirm the diagnosis using a blood test and anamnesis.

Immediate treatment is then required in any case. It is therefore advisable to consult a doctor at the first suspicion of the disease. Typical symptoms that must be clarified immediately are, in addition to the blue discoloration of the diapers, unusually frequent urination and sometimes pain when urinating.

Occasionally, other symptoms also occur and the affected child shows, for example, typical fever symptoms or seems exhausted. Therefore, with any symptoms that deviate from the norm, the pediatrician should be consulted.

If there are already cases of the disease in a family, the child and especially the stool should be examined as soon as possible after birth. A corresponding medical history enables a reliable diagnosis and facilitates the targeted treatment of the blue diaper syndrome.

Treatment & Therapy

A causal therapy is not available for patients with blue diaper syndrome until the causative gene has been identified and gene therapy approaches have not reached the clinical phase. Therefore, the disease is treated more or less symptomatically. Supplementation of the amino acid tryptophan can play a major role in such treatment. Since the disease does not allow tryptophan to be absorbed in the intestine, the amino acid must be administered in a different way.

Direct administration into the blood is recommended in this case. The supplementation of the amino acid reduces all symptoms of the metabolic disorder. In extremely severe cases, the hypercalcemia must be treated separately. For example, serum calcium can be lowered by increasing excretion, as can be achieved with a loop diuretic and glucocorticoids .

Symptoms such as nephrocalcinosis can only be treated by eliminating the hypercalcaemia. If the nephrocalcinosis has already led to renal insufficiency, this insufficiency requires separate treatment. Treatment options range from dialysis to transplantation , depending on the severity of the insufficiency .

As a rule, however, the blue diaper syndrome is recognized early enough to be able to successfully prevent kidney failure by permanently lowering the calcium level. Ideally, hypercalcemia will no longer occur in the future thanks to tryptophan supplementation.

Outlook & Forecast

The prospects for a cure are not given for the blue diaper syndrome. The syndrome is a genetic disposition that cannot be cured with the available medical and scientific options. For legal reasons, an intervention in human genetics is not permitted, which makes the prospects of recovery impossible. There are also no alternative healing methods or self-healing processes of the organism that contribute to improving health.

Without medical care for the consequences of blue diaper syndrome, the patient faces serious complications. In severe cases, organ failure of the kidneys occurs in untreated patients. This can lead to a sudden fatal course of the disease. The patient needs a donor kidney as soon as possible in order to improve their quality of life and maintain well-being.

The patient’s survival is assured if regular drug treatment is used. Although healing does not occur, the patient with the syndrome is able to manage his life independently. Overexertion and unnecessary stress are to be avoided, as is the consumption of alcohol or other harmful substances. If life is adapted to the needs of the organism and the lifestyle is designed to be as healthy and sustainable as possible, the general health of the patient improves immensely.

prevention

The blue diaper syndrome has not yet been conclusively researched. Neither the exact cause nor the possible influencing factors have undoubtedly been identified. Without knowing the influencing factors, the complex of symptoms cannot be prevented. The low prevalence of the syndrome is primarily responsible for the poor state of research. Due to this low prevalence, the research situation will probably not change much in the near future.

aftercare

With this extremely rare metabolic disease, medical follow-up care is essential because of the possible consequences of the disease. The positive effect of the strict diet that the affected children are on must be checked regularly. However, an unsuitable diet with too much calcium and the amino acid tryptophan can lead to kidney damage.

Intravenous tryptophan is preferable to dietary tryptophan. The injection is usually carried out under medical supervision or by medically trained nursing staff. In order to keep the blue diaper syndrome under control, therapies with antibiotics may be necessary if intestinal infections or bacterial infestation occur in the digestive system.

If kidney damage is already evident in those affected, follow-up care must monitor the resulting hypercalcemia and the prescribed loop diuretics and glucocorticoids. Follow-up care for blue diaper syndrome is complicated by the fact that tryptophan malabsorption has been poorly understood.

The metabolic disease is one of the very rare diseases. What is certain so far is heritability. Because blue diaper syndrome may be caused by a gene mutation, gene therapy may be able to provide better treatment outcomes in a few years. It remains to be seen whether medical follow-up care is still necessary or whether the blue diaper syndrome can be treated before birth.

You can do that yourself

Parents of children suffering from blue diaper syndrome simply need to ensure that the child is taking the necessary medication regularly and is not showing any noticeable symptoms or discomfort. If the treatment is carried out early, the development of renal insufficiency can be reliably avoided.

Affected children generally have no other symptoms or signs that require treatment other than blue urine. In individual cases, however, symptoms of the gastrointestinal tract or even serious kidney problems can occur. Parents should keep a close eye on their child and alert the pediatrician immediately if they notice any noticeable symptoms.

Despite its comparatively good prognosis, the disease can have an impact on the mental state of the parents, who often suffer from severe anxiety. A conscious examination of the blue diaper syndrome and its causes gives the relatives a new perspective on the disease and makes it easier to deal with it.

Visiting a support group or talking to other parents whose children have the metabolic disease can also help. Parents should contact the responsible doctor with their questions and concerns and consult a therapist through this doctor.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.