Screening for 58 neonatal metabolic disorders in Iran (Part 6 - Organic Acid Disorders)

Screening for 58 neonatal metabolic disorders in Iran (Part 6 - Organic Acid Disorders)


Following the previous discussion, we will examine one of the most important disorders that are screened during this process, namely organic acid disorders.

Organic acid disorders
- The hereditary pattern of these disorders is autosomal recessive, meaning that it is observed equally in girls and boys. That's why they are more common in consanguineous marriages.

The term "organic acid [1] or increase in organic acids in the blood" or "organic acid [2] or increase in organic acids in the urine" is used for a diverse and important group of inherited metabolic disorders with metabolic defects. Proteins in foods and the excretion of inorganic organic acids are identified.

Most organic acids are caused by a disorder at a certain stage of amino acid catabolism, usually due to a defect in enzymatic activity.

One of the first steps in the metabolism of an amino acid, which involves converting it to another amino acid and then removing the amine group from the second amino acid, increases amino acids in the blood and urine if there is an enzymatic defect. This group of diseases is one of the disorders of amino acids.

In the next one to two stages of metabolism of amino acids (which are very similar to the metabolism of fatty acids in fats), compounds called organic or organic acids are formed, and defects in these stages lead to the disruption of organic acids.

- This leads to the accumulation of organic acids, which are usually toxic, in biological fluids (blood and urine), which in turn leads to disturbances in the acid-base balance, physical-mental problems, as well as changes in metabolic pathways.

- On the other hand, the next metabolite that is located after the enzyme block and is one of the essential metabolites of the body is reduced and the body suffers from symptoms of deficiency of this substance.

For example, isovaleric acid disease (IVA) is caused by a defect in function or a lack of a special enzyme called iso-varyl coa dehydrogenase. The function of this enzyme is to break down a substance called iso-valerian coa. It is formed by breaking down the amino acid leucine in the body. When children with IVA receive leucine-containing foods, the level of iso-valeric acid in their bodies increases (leucine is found in all protein-rich foods).

- At least 20 different types of this type of disorder have been described, ranging from 1 to 20,000 to 1,000.


Clinical signs:
The symptoms of these diseases depend on the type of disorder and may vary from person to person. In general, the effects of these diseases depend on the age of onset, and these babies are generally healthy at birth, but the disease gradually progresses in the following days with symptoms such as not breastfeeding, general malaise, vomiting, tachypnea, acidosis, hyperammonemia, ketosis, ketonuria, Shows seizures, hypotension, and lethargy, findings that are in some ways indicative of neonatal septicemia.

Body odor in some patients with certain types of organic acid disorders such as
3-methylcrotonyl CoA carboxylase and multiple carboxylase deficiencies, due to the excretion of some organic substances, resemble the smell of cat urine, which can be a sign of a disorder in the metabolism of individual organic acids.


Neonatal screening:
• During the screening of metabolic diseases in infants 2 to 7 days of age using MS / MS testing, markers related to acyl carnitines are measured.

Among the markers measured during this screening are the profile of acetyl carnitine, which is considered as the primary marker for screening for organic acid disorders. If the result of the above tests is abnormal in Westernization, the MS / MS test should be repeated 1 to 2 days later with re-blood sampling. Obviously, if there is an enzymatic problem, the amount of these markers in the second sample will change more.

• Secondary markers: After confirming the increase of primary markers during the above two sampling stages, the changes of secondary markers during the two sampling stages are also calculated.
If these changes are observed in secondary markers, the individual's response is considered "outside the normal range" and is reported as a "suspicious" test for organic acid disorders, and confirmatory or diagnostic tests are recommended to confirm the diagnosis.

Diagnosis:
• The presence of pneumonic ketones in infants can be a characteristic feature of organic mimic acid, and it is recommended that these patients be tested for urine reducing agents.

• Measurement of acyl carnitines in the blood and urine

• Profiling of organic acids in urine.

• Measurement of enzyme levels in fibroblasts

• Performing genetic and molecular tests: Today, there are specific genetic tests (DNA tests) that can be used to determine whether a person is carrying a defective gene in the fetus' tissue or blood. If the type of disease is diagnosed before pregnancy, it can be detected by performing molecular tests on cells isolated during the amniocentesis process or CVS of these diseases in the fetus.

treatment:

The main purpose of treatment in these diseases is the following:
• Try to prevent the accumulation of toxic metabolites as well as compensate for the metabolic substance that is deficient

• Removal of toxins accumulated in the body by methods such as fluid administration (to compensate for the lack of breastfeeding, increase fluid flow and ensure effective excretion of toxic metabolites)
• Vitamin therapy (as therapeutic cofactors in cases of deficiency and deficiency of related groups and increased metabolism)
 
Treatment depends on the type of disorder, for example in isovalic acid myosin leucine should be eliminated from the diet. Therefore, accurate and rapid diagnosis of these diseases is very important in order to start effective treatment.

It is helpful to avoid prolonged fasting and a low-protein diet and to give carnitine supplements to the baby. Of course, in some disorders we need to prescribe other supplements. It is essential to prevent ketoacidic crises and treat them severely and effectively when a ketoacidic crisis occurs (such as by injecting glucose).
 
How to track patients after diagnosis:
• Parents of these patients should be taught that they need lifelong treatment and that it is mandatory to follow the nutritional tips of these patients in order to have a normal growth, health and developmental process.

• These patients should be monitored regularly by a metabolic specialist.

• Parents should be instructed to see a pediatrician immediately if they experience early signs of illness, such as vomiting and lethargy. The treatment plan should be given urgently by a metabolic specialist and immediate treatment should be given to prevent the disease from progressing to the critical phase.

• Long-term follow-up should be recommended to parents to keep the baby healthy. Consultations with a group of counselors, including pediatricians, geneticists and nutritionists, should also be conducted, and parents should be aware that the slightest violation of the diet can lead to the death of their child.

• Genetic counseling is recommended for the molecular diagnosis of the disease and to determine the risk of the next child being infected if they decide to become pregnant in the future.

      

RelatedNews Screening for 58 neonatal metabolic disorders in Iran (Part 6 - Organic Acid Disorders)

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