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Attention deficit hyperactivity disorder (ADHD) caused by DAO deficiency

Attention Deficit Hyperactivity Disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is a disorder that is more common in children and is associated with increased motor activity and decreased attention. It is a behavioral syndrome with a neurobiological basis that has a strong genetic component. It is a very common condition that affects between 5 and 10% of adolescents and is about 3 times more common in men. No differences have been demonstrated between geographical areas, cultural groups or socio-economic levels. It represents between 20 and 40% of the consultations in psychiatric services for children and adolescents.

It is a neurological behavior disorder characterized by moderate to severe distraction, attention deficit disorder, restlessness, motor and emotional instability, and impulsive behavior. Although it was initially identified in children, the condition is recognized as a diagnosis of a chronic nature, since it is still present and manifests itself after adolescence. Long-term studies show that between 60 and 75% of children with ADHD continue to show symptoms in adulthood.

The main features of ADHD are:

  • Difficulty maintaining concentration (attention deficit disorder), especially in circumstances that provide low stimulation;
  • Lack of inhibition or cognitive control of impulses (motor hyperactivity-impulsivity).

These two groups of symptoms may occur separately or in combination.

Symptoms of ADHD fall into three groups:

  1. Lack of attention;
  2. Hyperactivity;
  3. Impulsive behavior.

Some children with ADHD suffer mostly from a lack of attention. Others may have a combination of several symptoms. Children who are neglected are less anxious and are more likely not to be diagnosed with ADHD.

Symptoms of inattention in children are:

  • Fails to pay attention to details or makes uncaring mistakes in school work;
  • There are difficulties in maintaining attention in tasks or games;
  • He doesn’t seem to listen when he’s being spoken to directly;
  • He does not follow the instructions and fails to complete school or homework;
  • There are difficulties in the organization of tasks and activities;
  • Avoid or dislike engaging in tasks that require constant mental effort (such as school work);
  • Often loses toys, pencils, books or tools necessary for tasks or activities;
  • Easily entertained
  • They often forget when performing daily tasks.

Symptoms of hyperactivity are:

  • He frequently plays with his palms or feet and does not stand still;
  • It leaves the place when it is expected to stand;
  • Run excessively in inappropriate situations;
  • It is difficult to play in silence;
  • He often speaks excessively and loudly, with many gestures.

Symptoms of impulsivity are:

  • Answer before you hear the question to the end;
  • He finds it hard to wait for his turn;
  • Pause or join others (in conversations or games).

Diagnosis of attention deficit hyperactivity disorder (ADHD)

Too often, difficult children are incorrectly classified as children with attention deficit hyperactivity disorder. On the other hand, there are many children who are really left undiagnosed. In both cases, the difficulties associated with the learning process or frequent changes in the child’s mood are often overlooked. The American Academy of Pediatrics (AAP) has issued guidelines to clarify this issue.

The diagnosis is based on very specific symptoms that must be present in several scenarios:

  • Children should have at least 6 symptoms of attention deficit disorder or 6 symptoms of hyperactivity and impulsivity, and some symptoms are present before the age of 7.
  • Symptoms must be present for at least 6 months, be observed in two or more scenarios and not be caused by another problem.
  • Symptoms should be severe enough to cause significant difficulties in many ailments, including home, school and peer relationships.

The child should be evaluated by a health professional if ADHD is suspected. This process includes:

  • Questionnaires for parents and teachers (e.g. Connors, Burks)
  • Psychological evaluation of the child and family, including IQ research and psychological tests
  • Assessment of mental, nutritional, physical, psychosocial and general development
In older children, ADHD is in partial remission when they still have symptoms, but no longer meet the full definition of the disorder.

Depression, lack of sleep, learning difficulties, tic disorders and behavioral problems can be confused or co-occur with ADHD. When a child is suspected of having this disorder, it must be carefully examined by a specialist in order to exclude other conditions or possible causes of this behavior.

History in the treatment of ADHD

The symptoms of ADHD express a biological problem and have so far been addressed by pharmacological treatment, which is still the most important therapeutic pillar for many professionals. In fact, in many cases, drugs only aggravate the condition.

The usual treatments are paradoxically based on stimulants that positively change the symptoms. These include amphetamine, caffeine and nicotine, which are sometimes used to treat adolescents and adults. The first report demonstrating the effectiveness of psychostimulants dates back to 1937 and is devised by Charles Bradley. Establishes the efficacy and apparent safety of amphetamine sulfate for the treatment of overactive children.

Currently, the substances most used in the United States are methylphenidate (the active principle behind the trade name Ritalin) and d, 1-amphetamine, followed by dexamphetamine and methamphetamine. Other psychostimulants, second-line drugs in the treatment of ADHD, are pemoline and modafinil.

In recent years, drugs with immediate action tend to be replaced by another 50 drugs that, with the same active principles, achieve an effect of longer duration. The use of many of these drugs has been and is in doubt because of their numerous side effects.

Although stimulants are the first line in the treatment of this condition, some antidepressants such as fluoxetine, bupropion, venlafaxine, and desipramine have shown some benefit, especially when ADHD is present with comorbidities such as depressive disorders or anxiety (for example, generalized anxiety disorder).

As with other psychopathologists whose treatment is mainly pharmacological therapy, the methodology for diagnosing and treating ADHD is subject to serious debate, especially in the last 10 years.

Psychological treatment of behavioral problems related to the disease is also accepted. This type of intervention complements pharmacological treatment and usually seeks to diminish the destructive behavior of the child in different settings through therapies framed in cognitive-behavioral interventions.

In some cases, psycho-pedagogical intervention is also recommended for learning problems that usually occur in a large proportion of ADHD subjects. Currently, positive development therapies are being developed for children who are trying to improve the potential aspects of young people through sports and group dynamics.

Various researchers have developed models of working with groups of children with ADHD and it has been found that a well-managed group gives better results than individual therapy. In this way, aspects such as self-esteem and social skills can be targeted.

Research and proposal for medical assistance in the treatment and diagnosis of ADHD caused by DAO deficiency

The role of histamine in the etiology of ADHD

Histamine [2- (4-imidazolil) -ethylamine] is an important mediator of many biological processes, including inflammation, gastric acid secretion, neuromodulation and regulation of immune function.

Due to its strong pharmacological activity, even at very low concentrations, it is necessary to carefully regulate the synthesis, transport, storage, release and degradation of histamine, in order to avoid side effects. High levels of circulating histamine have been reported that cause side effects such as headaches, migraine headache, runny nose congestion or runny nose, airway obstruction, tachycardia, gastrointestinal disorders, irritable bowel syndrome, muscle pain or fibromyalgia, erythema skin rash, lowering blood pressure or bronchospasm.

Histamine is produced in the body and stored in inactive form in the metachromatic granules of mast cells and basophils, where it is available for immediate release. After release, histamine is an extremely powerful mediator of many physiological and pathophysiological processes, often through interaction with cytokines.

Histamine can also enter the human body from the outside, since it is generated by microbial action in the process of food processing, and therefore it is present in significant amounts in many fermented foods and beverages.

The enzyme diamin oxidase (DAO): a new biomarker for ADHD

The main inactivation route of absorbed histamine is the oxidative disinmination of the primary amino group, catalyzed by diamin oxidase (DAO), a process that leads to imidazole acetaldehyde. The main function of DAO is to prevent ingested histamine from reaching the bloodstream.

In addition to histamine, DAO can degrade other biogenic amines such as putrescin, spermidine and cadaverine.

DAO has a molecular weight of about 182 kDa. It belongs to the class of copper-containing amino acids that catalyze the oxidative deamination of primary amines to produce aldehydes, ammonia and hydrogen peroxide. DAO uses molecular oxygen to deaminate histamine to imidazolacetaldehyde, ammonia and hydrogen peroxide by oxidation.

In addition to inhibiting DAO by certain types of substances, there is a significant percentage of patients suffering from low levels of DAO in the blood. This means that the level of histamine in the blood is higher than the values considered normal (2-20 micrograms / 0.1 L). These people suffer from a number of pathologies caused by these high levels of histamine.

Clinical data on ADHD associated with DAO deficiency: treatment

Dr Healthcare, a nutraceutical research company, found that about 80% of children with ADHD also have a congenital defect in DAO activity, so histamine is not metabolized and accumulates in the body.
The problem is complicated by the fact that most of the drugs prescribed in the treatment of ADHD are inhibitors of DAO activity. In the long term, taking these drugs creates chronic symptoms and addiction, which leads to the need to increase the dose.

Therefore, determining the activity of DAO is a new and important biomarker for the objective diagnosis of ADHD, both through genetic testing of genotypes that are associated with DAO deficiency, and by measuring DAO plasma activity, or a combination of both.
The use of a DAO supplement in children and adults diagnosed with ADHD has been shown to significantly improve the symptoms that characterize attention deficit hyperactivity disorder. This eliminates pharmacological treatment and its adverse effects.


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