A rare genetic disorder recently discovered by researchers at UT Southwestern Medical Center and their partners may cause serious health problems in both infants and adults.
The disorder, which is linked to a mutation in a gene called ACAA2, can lead to low blood sugar, liver damage in babies, and several metabolic issues in older children and adults. The findings were published in The Journal of Clinical Investigation.
Dr. Abhimanyu Garg, the lead researcher of the study and a professor of internal medicine, explained that the mutation can either be inherited from a parent or happen on its own. He encouraged doctors to consider testing for this gene mutation in infants who have unexplained low blood sugar or liver problems.
Early diagnosis, especially in babies, could help prevent brain damage caused by low blood sugar and reduce the risk of long-term liver damage.
The disorder appears to be a new form of familial partial lipodystrophy (FPL), a condition where fat is lost from certain areas of the body like the arms and legs, and builds up in other places like the trunk and neck. Some people with FPL also develop soft fatty tumors called lipomas on their upper backs.
These patients often suffer from metabolic problems, including fatty liver disease, high cholesterol, and type 2 diabetes. Dr. Garg has spent three decades studying different genetic causes of FPL.
Mitochondria are tiny parts of cells that help turn food into energy, and they rely on fats to do this. Enzymes, including one called ACAA2, help break down these fats in a process known as mitochondrial fatty acid oxidation.
In the newly found mutation, one part of the ACAA2 enzyme changes, which may cause it to become overactive. This change could disturb how the body processes fats and leads to health issues.
One of the signs that doctors can look for in this disorder is high levels of certain fatty acid-related molecules called long-chain acylcarnitines in the blood. These may serve as markers to help diagnose the condition.
In the study, four families were found to have this rare genetic change. Among the patients, several had liver problems during infancy. Two of them had liver biopsies that showed fat buildup in the liver, scarring, and damage to the mitochondria.
One child from these families had such low blood sugar as a baby that it caused brain damage. This is because the disorder blocks the body from making ketones, which are used as backup energy when glucose is low.
Now that this genetic mutation has been discovered, researchers hope to create models of the disease to study it more closely and test new treatments. Dr. Garg also wonders if other versions of the ACAA2 gene mutation might be linked to more common conditions like diabetes or fatty liver disease.
In the future, special diets or new drugs might help lower the harmful fat-related molecules in the blood and improve health for people with this disorder. This discovery may lead to better diagnosis and treatments for people who have been suffering without knowing the cause of their symptoms.
If you care about liver health, please read studies about simple habit that could give you a healthy liver, and common diabetes drug that may reverse liver inflammation.
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