Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare, inherited metabolic disorder that disrupts the body’s ability to break down certain fats for energy. This becomes particularly problematic during periods of fasting, such as overnight or during an illness, when the body relies on fat stores for fuel. The condition impairs the conversion of long-chain fatty acids into a usable energy source. As a result, these fats cannot be properly processed, leading to a range of health issues.
Genetic Causes of LCHAD Deficiency
LCHAD deficiency is an autosomal recessive disorder, meaning a child must inherit two non-working copies of the responsible gene—one from each parent. The parents are carriers, who each have one functional and one non-working copy of the gene but do not show signs of the disorder. When both parents are carriers, there is a 25% chance with each pregnancy that the child will inherit the condition.
The specific gene implicated is the HADHA gene, which provides instructions for making part of an enzyme complex necessary for breaking down long-chain fatty acids. When mutations occur in both copies of the HADHA gene, this enzyme complex cannot function correctly. This genetic error causes an energy deficit and a harmful buildup of partially metabolized fatty acids.
Signs and Health Complications
The initial signs of LCHAD deficiency most often appear in infancy. Affected babies may exhibit poor feeding, a general lack of energy known as lethargy, and vomiting. Two of the most common early indicators are weak muscle tone (hypotonia), which can make an infant seem “floppy,” and dangerously low blood sugar (hypoglycemia).
These early symptoms can quickly escalate into a life-threatening event known as a metabolic crisis. Such a crisis is frequently triggered by common stressors like a viral illness or a period of fasting. During a metabolic crisis, the buildup of unprocessed fatty acids can become toxic, leading to severe complications without prompt medical intervention.
LCHAD deficiency can lead to significant long-term health complications, including:
- Hepatopathy, a liver condition caused by the accumulation of fatty acids.
- Cardiomyopathy, a disease of the heart muscle.
- Rhabdomyolysis, the severe breakdown of muscle tissue that releases damaging proteins into the bloodstream.
- Progressive damage to the retina, the light-sensitive tissue at the back of the eye, which can cause vision problems.
The Diagnostic Process
The diagnostic process for LCHAD deficiency commonly begins with newborn screening. A small blood sample is taken from the baby’s heel to test for several conditions. For LCHAD, this screening looks for elevated levels of specific substances called acylcarnitines. An out-of-range result from this initial screen is not a final diagnosis but indicates that more testing is needed.
Following an abnormal screen, confirmatory tests are performed. These include detailed blood tests to analyze the pattern of acylcarnitines and urine tests that check for certain organic acids, which are also byproducts of incomplete fat metabolism.
A definitive diagnosis is established through genetic testing, which analyzes the individual’s DNA to identify two disease-causing mutations in the HADHA gene. This genetic confirmation also allows for genetic counseling for the family regarding future pregnancies.
Core Treatment Strategies
The management of LCHAD deficiency revolves around a highly specialized and strict dietary plan. The primary goal is to prevent the body from needing to break down long-chain fats for energy. This is achieved through a diet that is low in fat and high in carbohydrates, ensuring a constant and easily accessible source of glucose.
A necessary component of this diet is the use of medium-chain triglyceride (MCT) oil. MCT oil is a special type of fat that the body can absorb and use for energy without needing the defective enzyme. It effectively bypasses the metabolic block, providing a safe fuel source, and is carefully calculated by a dietitian.
Strict avoidance of fasting is a non-negotiable part of treatment. For infants, this means frequent, scheduled feedings, including throughout the night, to prevent blood sugar from dropping. As children get older, they must eat at regular intervals and have an emergency plan for sick days, which often requires medical intervention to provide intravenous glucose.
Long-Term Health Management
Living with LCHAD deficiency requires lifelong, proactive health management coordinated by a multidisciplinary team of specialists. This team often includes:
- A metabolic specialist who leads the overall care.
- A registered dietitian to manage the complex diet.
- A cardiologist to monitor heart health.
- An ophthalmologist to track vision.
The focus of long-term management is surveillance through regular appointments and routine tests to detect and address potential complications before they become severe. For example, individuals undergo periodic echocardiograms to check for cardiomyopathy and receive regular, detailed eye exams to monitor the health of the retina.
Diligent adherence to the prescribed diet, avoidance of fasting, and regular medical monitoring are necessary to manage the condition. This careful, continuous care helps prevent metabolic crises and minimize long-term complications, allowing individuals to lead full lives.