Inherited Metabolic Disorders - Causes, Symptoms, and Diagnosis

What Are Metabolic Disorders?

Metabolic disorders result from abnormal chemical reactions in the body; these reactions cause changes in the body process due to abnormal increases or decreases in the enzymes that control reactions. These metabolic disorders increase the risks of medical conditions like heart disease, diabetes, obesity, and abnormal cholesterol and triglyceride levels.

What Are Inherited Metabolic Disorders?

Inherited metabolic disorders, which are also called inborn errors of metabolism, are genetically inherited and have an autosomal recessive inheritance pattern. Many known inherited metabolic disorders exist, like albinism, cystinuria, and phenylketonuria; though there are many metabolic disorders, these are among the rare conditions. These disorders are caused as a result of enzyme deficiency.

What Are the Causes of Inherited Metabolic Disorders?

There of a wide variety of metabolic disorders, but most of the metabolic disorders that are encountered are rare among the population. Any metabolic disorder that is diagnosed is seen in one of 1000 individuals. Alterations in enzyme secretion and metabolism cause most metabolic disorders. These disorders are presented when both parents are carriers of the disease and pass on the affected genes. Metabolic disorders develop as a result of gene mutation, and the defects are passed on to many further generations. The absence of enzymes in the body affects the system's functioning by depositing toxic substances and leading to a deficiency of essential products. These conditions are more common among the Jews. Some common inherited metabolic disorders are:

• Phenylketonuria (PKU): Phenylketonuria is a metabolic disorder resulting from the defect in the PAH gene, which leads to increased levels of enzyme phenylalanine in the blood. This condition leads to intellectual disabilities if not diagnosed at the earliest.

• Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD): Medium-chain acyl-CoA dehydrogenase (MCADD) deficiency is inherited. This condition is characterized by the deposition of excessive fat in the body as a deficiency of the enzyme prevents the metabolism of the fat into energy. This leads to low levels of blood sugar levels.

• Maple Syrup Urine Disease (MSUD): The condition is caused by a deficiency of an enzyme called BCKD, which results in the deposition of amino acids in the body. This leads to damage to the nervous system, and the condition presents a characteristic syrup-like odor in the urine.

• Isovaleric Acidaemia (IVA): Isovaleric acidemia is a rare inherited metabolic disorder. Patients with isovaleric acidaemia have a defective amino acid mechanism. These individuals cannot process the amino acid leucine, which results in the deposition of harmful substances in the blood and urine.

• Glutaric Aciduria Type 1 (GA1): Itis a metabolic disorder where a body fails to process amino acids. Patients with these disorders face difficulty digesting meats as the body cannot break down this product into amino acids.

• Homocystinuria (Pyridoxine Unresponsive): A rare metabolic disorder that results in difficulty processing the amino acid methionine.

Some Other Metabolic Disorders Are

• Hurler syndrome (a disorder caused by a deficiency of a lysosomal enzyme that helps in the breakdown of dermatan sulfate and heparin sulfate (GAG). It leads to the accumulation of large amounts of GAG in the body, making the cells become highly dysfunctional, causing death).

• Niemann-Pick disease (a group of inherited metabolic disorders characterized by abnormal amounts of lipids, fatty materials like waxes, oils, and cholesterol that accumulate in the brain, spleen, liver, lungs, and bone marrow).

• Tay-Sachs disease (a progressive, deadly neurodegenerative disorder as a result of deficiency of enzyme hexosaminidase).

• Gaucher disease (disorder as a result of a buildup of some fatty products in some organs, especially the spleen and liver).

• Mitochondrial disorders (a group of genetic disorders that affect the mitochondria in the cells that produce energy).

What Are the Symptoms of Inherited Metabolic Disorders?

The symptoms of the metabolic disorder are based on the type of inherited condition. Therefore, the condition presents a variety of symptoms, including

• Lethargy.

• Poor appetite.

• Vomiting.

• Weight loss.

• Developmental abnormalities and delayed growth spurts.

• Jaundice.

• Seizures.

• Coma.

• The odor of urine.

• Weakness.

These symptoms may appear at birth or develop slowly over the years. The conditions are even affected by certain food habits or lifestyle patterns.

How Are Inherited Metabolic Disorders Diagnosed?

Every state has routine screening tests for newborns, which help determine the metabolic disorders at birth. To date, the states have been screening for phenylketonuria; galactosemia (some of the metabolic disorders). The symptoms of some disorders that are not presented during the screening or at birth appear during later stages of life and require more advanced diagnostic tools. Specific blood and DNA tests are available to diagnose the conditions when the symptoms appear.

Advances in the diagnosis and treatment of the condition have helped in improving the prognosis of the condition. Laboratory tests for these conditions include monitoring for:

• Hypoglycemia or Low Blood Sugar Levels: Blood glucose levels are monitored as low blood glucose levels are very common findings in the inborn with metabolic disorders.

• Jaundice: It is also one of the important findings as most of the enzymes that are absent of malfunctioning are present in the liver. Therefore, it also helps in diagnosing the condition at the earliest.

How Are Inherited Metabolic Disorders Treated?

There were very few treatment options available to overcome the symptoms and the problems caused by metabolic disorders, as these conditions being genetically inherited, cannot be cured; therefore, the treatment mainly aims at correcting the problems of metabolism.

Following are some measures that helped overcome metabolic problems:

• Avoid or prevent food and medications that cannot be metabolized or tolerated by the body.
• Supplements of the missing enzyme should be provided to replace the missing enzyme to help them function normally.

• Measures should be taken to eliminate the toxins deposited in the body due to metabolic malfunction. But recent advances and scientific studies have enabled the procedures like gene replacement therapy, gene transfer, or organ transplantation. These treatments have helped in overcoming the issues faced over decades.

• Individuals with inherited disorders require care and attention therefore, if required, these subjects must be referred to a psychotherapist for counseling and have access to medical services during emergencies, as they can require medical help at any hour.

Conclusion

Metabolic disorders are genetically inherited autosomal recessive disorders due to alterations in enzyme secretion and regulation. These disorders are diagnosed at birth as newborns present with some of the symptoms mentioned above. Some symptoms diagnosed later during the lifetime or misdiagnosed require advanced diagnostic tools. These disorders or conditions are difficult to diagnose and have no known cure therefore, measures are taken to prevent the symptoms and any undue effects due to lack of energy or deposition of toxins in the body. Recent advances like gene replacement therapy or gene alterations help overcome the condition to a great extent but still have no definitive treatment for a complete cure.