More than hundreds of hereditary metabolic diseases have been identified so far, many of which are complex and require complex diagnostic methods. One of these methods is the MS/MS Spectrometry (TMS) technique, which is available in most of the world's reputable centers for Screening and identification of metabolic diseases are used. Congenital metabolic diseases that can be identified with this method are more than 30 diseases that are divided into three main groups:
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Disorders of amino acids
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Fatty acid disorders
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Disorders of organic acid metabolism
With the help of this advanced technology, all cases caused by these three categories of diseases can be identified in a short time, but a limited number of diseases are selected for screening programs. The criterion for this choice is the treatability of that disease, the possibility of preventing irreversible complications, and the existence of a confirmation method for definitive diagnosis of the disease. Therefore, it is never possible to include all metabolic diseases in the screening program because in many cases there is no effective treatment for them. Curable cases also often require special diets and consumption of dietary milk and sometimes special drugs, and even with these measures, definitive treatment is not possible and only the occurrence of disease complications can be prevented. Therefore, it is important to identify untreatable cases because it is possible to prevent the next child from getting infected in future pregnancies with the help of genetic diagnostic methods by performing a prenatal test(PND) on a CVS sample or amniocentesis.
Metabolic Disorders of Amino Acids
Amino acids are the small building blocks of proteins in the body, there are about 20 types of amino acids in the body, and many enzymes work to build or break them down in the body. The deficiency of some of these enzymes causes the reduction of some amino acids and the accumulation of others and causes toxic effects on the body, especially on the brain. The symptoms of this group of diseases are different depending on the type of enzyme defect and the type of substance that accumulates. Even in people with an enzyme deficiency, the symptoms are not the same, and depending on the severity of the enzyme deficiency, the symptoms vary. These patients are completely normal at birth and do not have any symptoms, and over time, following the consumption of milk and the accumulation of toxic substances, or following stress (which in babies is usually long hunger or infection), symptoms gradually appear. General symptoms are hypoglycemia, lethargy, lack of feeding, restlessness, seizures, lack of weight gain, developmental delay, lack of head growth, movement disorders, excessive stiffness or laxity of muscles, liver involvement, and coma. In case of symptoms, the treatment is usually difficult, and in the case of successful treatment, the complications caused by the disease often remain. Therefore, it is necessary to identify and treat these diseases before they become symptomatic. With timely treatment, the mentioned side effects can be prevented to a great extent and provide a healthy life for the child. Most of these diseases are inherited as autosomal recessive.
Fatty acid metabolic disorders
About 1/3 of the energy needed by the body comes from fat, which is mainly found in the form of triglycerides in food sources such as vegetable oils, dairy products, meat, fish, etc. After fat digestion in the small intestine, fatty acids are released and enter the liver with the bloodstream and lymph system, where they are metabolized. Fat breakdown must be done in the cell and inside the mitochondria, and to enter the mitochondria for fatty acids that have a long chain, a carrier called carnitine is needed, the lack of which can disrupt the process of fat metabolism. Fatty acid metabolism disorders are a group of metabolic diseases in which the enzymes related to the oxidation of fatty acids in the mitochondria have activity disorders and energy production in the body is disturbed. On the other hand, ketone production, which is itself a source of energy and is produced in the final stages of fatty acid metabolism, is disturbed and causes more sugar drops in these patients. The general symptoms of these diseases include low blood sugar, frequent vomiting, liver failure, muscle weakness, heart problems, seizures, and coma, and the set of symptoms of this metabolic crisis is called a pseudo-Ray syndrome. Unlike most other metabolic diseases, where sugar drop is associated with increased ketone production, in these patients, urine ketone is negative or insignificant, which helps to diagnose the disease.
Metabolic disorders of organic acids
Organic acids are a group of organic acids in the body that are produced as a result of disruption in the metabolism of amino acids or fatty acids and accumulate in body fluids and have toxic effects on the body and especially the brain. Several enzyme defects in this pathway cause organic acid, whose symptoms are different depending on the type of organic acid that accumulates, and even in one type of organic acid disorder, the symptoms vary from person to person depending on the severity of the enzyme defect. The prevalence of diseases alone is low, but it includes 1.200,000 live births.
Most babies do not have any symptoms for a few days to a few weeks after birth, and following the consumption of milk and protein and the accumulation of organic acids, the symptoms gradually appear. The general symptoms of these diseases are due to the accumulation of acid and ammonia and the drop in sugar in the body, which is collectively known as a metabolic crisis, which includes sleepiness, lethargy, anorexia, lack of weight, frequent vomiting, rapid breathing, liver failure, and anemia. - Loss of blood calcium - Abnormal stiffness or laxity of muscles - Abnormal head growth - Seizures and coma, which lead to the child's death if not treated on time. diagnosis The disease can be detected by a screening test from a drop of blood from the heel in the first few days of birth and after the start of feeding. By increasing metabolites related to organic acid, the type of disease can be identified. A urine sample is needed to check the type of organic acid and as a supplementary test. Also, unlike fatty acid disorders, in this type of disorder, the amount of ketones in the urine is very high, which can help differentiate these two disease groups. Genetic tests can be used to confirm the diagnosis. Genetic testing also helps in prenatal diagnosis (PND) on CVS samples or through amniocentesis to prevent the birth of the next affected child. For this purpose, the pathogenic mutation must be determined in the affected baby and carrier parents before pregnancy so that the PND test can be performed in the next pregnancy.
Treatment of all disorders with restriction of protein consumption (vega and fat) - consuming more sugary substances and avoiding long-term fasting - using dietary milk in some special cases - using drugs to treat blood acid and increase ammonia (such as bicarbonate, sodium benzoate, and phenylbutyrate) And sometimes dialysis is needed to get rid of acid or ammonia. Finally, in some cases that do not respond well to treatment, liver transplantation may help. The most common types of these disorders are methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and glutaric acidemia type 1. Sometimes dark throat acidemia type 2 is also classified under this category, which is mentioned in the topic of fatty acid oxidation disorders. The inheritance of most types of these disorders is autosomal recessive.