Organic Acidemia - An Overview

Introduction

Proteins play an essential role in the human body because they have many functions, such as muscle strengthening, metabolic reactions, tissue buildup, and many more. The breakdown of the proteins to release energy (metabolism) is one of the important functions.

If this metabolism gets hampered, it may result in abnormal body functioning, including poor development, retardation, poor functioning of the nervous system, and so on. Sometimes, the specific enzymes do not break the proteins appropriately, resulting in the abnormal accumulation of molecules or chemicals in the blood. This leads to toxicity in the blood and can be treated by modifying diet and other supplements. Acidemia is a condition in which the hydrogen ion levels increase in the blood. This results in low pH blood levels and high acidity blood. Acidemia is sometimes interchangeably used with aciduria.

What Is Organic Acidemia?

It is a group of rare genetic metabolic disorders in which the enzymes do not work appropriately to break down the proteins resulting in the abnormal accumulation of molecules or chemicals in the blood. This results in the toxicity of the blood. It is also called organic aciduria.

What Is the Epidemiology of Organic Acidemia?

Commonly, organic acidemia is seen in severely ill children and newborns. It is a rare disorder in England, the United States of America, and other western countries but is common in Asia, such as India. It equally occurs in males and females.

Causes of Organic Acidemia:

It is typically caused by the deficiency or complete absence of specific enzymes involved in the metabolism or breakdown of the amino acids and mutation in the DNA sequences.

Classification of Organic Acidemia:

It is classified into five groups:

1. Branched-Chain Organic Acidemia - In this disorder, branched-chain amino acids (leucine, isoleucine, and valine) do not break down due to abnormal enzyme action.

2. Multiple Carboxylase Deficiency - It occurs because of the lack of holocarboxylase synthetase, an enzyme that increases the activity of vitamin biotin.

3. Glutaric Aciduria - It occurs because of a deficiency of glutaryl CoA dehydrogenase enzyme resulting in the inappropriate breakdown of amino acids.

4. Fatty Acid Oxidation Defect - It occurs because of the deficiency of enzymes required for the breakdown of fats or fatty acids.

5. Energy Metabolism Disorders - It occurs because of the incomplete formation of the energy released from the breakdown of amino acids or proteins. It affects the nervous system of the patient.

What Are the Common Organic Acidemias?

The common organic acidemias are:

Methylmalonic Acidemia

• It is characterized by the deficiency of methyl malonyl CoA mutase enzyme.

• It results in poor growth and development of the newborn.

• Anemia.

• Development of metabolic ketoacidosis (high levels of acid in the blood).

Propionic Aciduria

• It is characterized by the deficiency of propionyl CoA carboxylase enzyme.

• It results in the presence of ketone bodies (acid) in the newborn's urine.

Isovaleric Aciduria

• It is characterized by the deficiency of the isovaleryl CoA dehydrogenase enzyme.

• It results in short-term episodes of ketosis (high levels of acid in the blood).

• Vomiting.

• The unusual odor of sweat, “sweaty foot odor.”

• Coma and death.

Maple Syrup Urine Disease

• It is characterized by the deficiency of branched-chain ketoacid dehydrogenase complex enzymes.

• It results in an odor similar to burning sugar in the urine.

• Mental retardation.

• Vomiting.

• Coma and death before the age of one year.

Glutaric Aciduria Type I:

• It is characterized by the deficiency of the glutaryl CoA dehydrogenase enzyme.

• It results in the involuntary contraction of the muscles.

• Muscle fatigue.

• Presence of glutaric acid in the urine.

Multiple Carboxylase Deficiency:

• It is characterized by the shortage of acetyl CoA carboxylase enzymes.

• It results in rashes on the skin.

• Hairfall or alopecia.

• Poor growth and development of the child.

What Are the Clinical Manifestations of Organic Acidemia?

• The newborn may suffer muscle weakness or even death within the first week of birth.

• Vomiting.

• Lethargy.

• Brain diseases due to toxins may stay for a lifetime as in encephalopathy.

• The functionality of any system within the body may deteriorate, such as poor heart pumping.

• Abnormal behavior changes.

• Dietary deficiencies in later stages of life.

How Is Organic Acidemia Diagnosed?

The presence of organic acids in the urine or blood sample is measured through the following tests:

1. Gas-Liquid Chromatography - A test that uses gas or liquids to separate toxins from the urine sample. The results show the presence of organic acids or toxins 100 times more than the normal levels. More than 1000 organic acids are easily detected through this test.

2. Mass Spectrometry - It is performed with chromatography to measure the mass of the molecules or atoms to identify the composition of the chemicals in the sample. It helps in detecting the presence of amino acids in the urine.

3. High Field Proton Nuclear Magnetic Resonance (NMR) - It is a test based on advanced technology to detect organic compounds in the sample.

How to Manage Organic Acidemia?

1. Nutritional Therapy - The patient must take a diet based on an amino acid formula to ensure a low protein diet. The diet may be rich in vitamins as these help in biochemical reactions.

2. Synthetic Amino Acid Formula - This formula must provide 50 % of the daily requirement of the proteins.

3. Avoid Fasting - The patient must avoid starving.

4. Supplements - The doctor may prescribe biotin and carnitine supplements to the patient to support the removal of toxins from the body.

5. Electrolyte Balance - The fluid-electrolyte imbalance and blood pH must be corrected through hydration to treat acidosis.

6. Dialysis - If the acid levels are high in the blood, then dialysis is required. It is done by removing toxins and waste products from the body.

What Is the Differential Diagnosis of Organic Acidemia?

• Mevalonic Aciduria - A disorder in which there is an abnormal synthesis of cholesterol resulting in the presence of mevalonic acid in the urine.

• Glutaric Aciduria - A disorder in which there is abnormal oxidation of the fatty acids resulting in the presence of multiple organic acids in the urine.

• Biotinidase Deficiency - A disorder in which the body fails to recycle the vitamin biotin resulting in the excretion or presence of organic acids in the urine.

• Mitochondrial Disease - A disease in which the energy production by the mitochondrial cells becomes disrupted, resulting in abnormal levels of organic acids in the urine.

• Urea Cycle Disorders - A disorder in which the body fails to remove the ammonia from the blood resulting in the excretion of organic acids in the urine.

Conclusion:

Organic acidemia, also called organic aciduria, is a rare disease related to abnormal or defective genetic mutations. As a result, the enzymes do not work appropriately to break down the proteins resulting in the abnormal accumulation of molecules or chemicals in the blood. It commonly occurs in newborns with various symptoms such as vomiting, muscle weakness, poor growth and development, and so on. The condition is best treated with a special diet and amino acid-based formulas to cut the intake of proteins.