What Is Isovaleric Acidemia?
Isovaleric acidaemia is a rare inherited condition where a body fails to process the amino acid leucine. The body's inability to process leucine increases the protein deposits in the bloodstream and urine. A normal process comprises the breakdown of leucine into a substance called isovaleric acid, which is then transformed into energy. In patients with isovaleric acidemia, the process is altered due to the absence of an enzyme that can potentially break down the amino acid.
What Are the Synonyms of Isovaleric Acidemia?
Various names known by which isovaleric Acidemia are:
- Isovaleric acid CoA dehydrogenase deficiency.
- Isovaleric acid.
What Are the Signs and Symptoms of Isovaleric Acidemia?
Signs and symptoms of IVA vary according to the severity of the mutation.. The symptoms can be mild to severe. Some of the most common signs and symptoms include:
- Lethargy.
- Poor feeding.
- Vomiting.
- Progressing to coma.
- Neutropenia.
- Pancytopenia.
- Hypothermia.
- Failure to thrive.
- Developmental delay.
The characteristic odor of sweaty feet is observed in these patients due to the buildup of isovaleric acid.
What Are the Causes of Isovaleric Acidemia?
Isovaleric acidemia is a genetic condition inherited as an autosomal recessive trait, and this disorder occurs due to the inheritance of faulty genes from both parents. In cases where an individual receives one normal and one faulty gene for the disease, that individual becomes an asymptomatic carrier for the disease. This gene mutation is seen in the IVA gene and results in the inactivation of enzyme isovaleryl-Co-enzyme A (CoA) dehydrogenase which helps in the breakdown of amino acid leucine into energy.
How Is Isovaleric Acidemia Detected?
Around the age of five days, newborns are now provided with newborn blood spot screening to detect the presence of isovaleric acidemia. This includes puncturing the baby’s heel to collect droplets of blood for testing. After diagnosing isovaleric acidemia, the treatment can be promptly administered to mitigate the risk of severe complications. With timely identification and appropriate treatment, most children with IVA can lead healthy lives. Yet treatment for IVA must be maintained indefinitely. Without treatment, life-threatening and severe symptoms can develop in some children, including fits or lapsing into a coma. Untreated IVA also poses risks of developmental delay and brain damage.
How Is Isovaleric Acidemia Treated?
As isovaleric acidemia results from a mutation in the gene, no definitive cure has yet been found for the disease. However, the prognosis is good when the disease is diagnosed at the earliest and early neonatal symptoms are treated at the earliest to avoid complications. Though the patient may be stable and does not present with any symptoms, he requires regular visits to the geneticist and follow-ups with the metabolic physician to check the progress and effects of the disease. These physicians help in controlling and managing organic acidemia. During the visit, the doctor monitors growth, development, diet, blood acid levels, and blood and electrolyte count. In severe cases, the nervous system and other vital organs are examined for any complications if present.
Symptomatic Treatment Includes
Diet Management: Metabolic dietitian tailors diet for children with IVA. This diet usually includes low-protein and high-sugar. These patients require low protein to avoid overconsumption of leucine. Protein intake should be sufficient to avoid other complications.
Breast milk contains a large amount of leucine. The dietician will provide a detailed amount, frequency, and feed volume guide. These children may also be advised to consume protein-free formula to replace baby milk and a balanced diet containing all vitamins, minerals, and other amino acids required by the child for normal growth and functioning. These children must follow a modified diet for the rest of their lives to prevent complications from metabolic crises. Constant visits and communication with the dietician can achieve this.
Medicinal Treatment:
Children with IVD might be put on medications to clear excessive isovaleric acid; some of the commonly prescribed medications include:
- L-carnitine.
- Glycine.
Both the medications mentioned above must be taken orally as advised by the doctor and daily. Doses and no of tablets to be taken daily depending on the disease's severity.
Emergency Treatment:
Emergency develops when protein and sugar intake balance is disturbed. In such cases, a child might suffer from indigestion and diarrhea and avoid having food. In such circumstances, the dietician may advise a low-protein and high-sugar diet. If a child cannot eat, a feeding tube is provided by the doctor, which is demonstrated at the time of handing over to the patient and is very easy to use, which can help in feeding patients high-sugar syrups or drinks administered through this feeding tube.
The chances of developing medical crises increase when the patient develops a high fever and cold due to a secondary infection. In such cases, prescribed medications should be continued, and additional antibiotics and analgesics must be taken as the physician advises. If the symptoms do not improve and the baby is still not feeding with a feeding tube, he must be taken to the emergency room; while going to the hospital emergency guide must be taken as it can be helpful in case the doctor has not treated any patient with IVA before. The patient will receive intravenous supplements in the hospital and can return to a normal diet within a few days after hospitalization.
How Is IVA Inherited?
IVA is passed to the children from parents through genetic mutation, and the children are affected when both parents are asymptomatic carriers of the disease. To inherit the condition, a child must receive two copies of mutated genes, one from both parents. Thus this type of inheritance is called autosomal recessive inheritance, where a single affected gene cannot express the disease. In cases where both parents are carriers, the chances of developing the disease in children are as follows:
-
1 in 4 develops the disease.
-
1 in 2 are the carriers.
-
1 in 4 has normal genes.
As it is impossible to prevent the disease, doctors must be informed of the family history if present. This can help take early measures and monitor the child to prevent further complications.
Conclusion:
Isovaleric acidaemia is a genetic disorder with autosomal recessive inheritance. These children cannot metabolize amino aid leucine and convert it into energy. They are usually diagnosed during early childhood as they have difficulty digesting the baby's milk, are lazy, and are smelly. No definitive treatment is available, but the patient is treated symptomatically and maintained through diet control.
