Medium-chain acyl-CoA dehydrogenase deficiency, or MCAD deficiency, is an inherited metabolic disorder that prevents the body from converting certain fats into energy. This process is important during periods of fasting, such as overnight or between meals. Without the ability to break down medium-chain fatty acids, the body is deprived of an energy source, which can lead to a drop in blood sugar.
The condition is caused by a deficient medium-chain acyl-CoA dehydrogenase enzyme. A genetic mutation impairs this enzyme’s role in fatty acid oxidation. This means when glucose is low, the body cannot turn to its fat reserves for energy, leading to the onset of symptoms.
The Genetic Basis of MCAD Deficiency
MCAD deficiency is inherited in a pattern known as autosomal recessive. This means a child must inherit two copies of the mutated ACADM gene to have the condition, one from each parent. A mutation in this gene leads to the production of a non-functional or less effective enzyme.
Parents who each have one copy of the mutated gene are known as carriers. They do not show any signs or symptoms of the disorder because their one functional copy of the gene is sufficient to produce enough of the enzyme.
When two carriers have a child, there is a 25% chance with each pregnancy that the child will have MCAD deficiency. There is also a 50% chance the child will inherit one mutated gene and be a carrier, and a 25% chance the child will inherit two functional genes and be unaffected.
Newborn Screening and Diagnosis
Most individuals with MCAD deficiency are identified shortly after birth through routine newborn screening programs. These programs are standard in many countries and aim to detect conditions before symptoms develop. The process involves a heel prick test, where a small sample of the baby’s blood is collected.
This blood sample is sent to a laboratory for analysis using tandem mass spectrometry. This technology can detect abnormal levels of specific substances, known as acylcarnitines. For MCAD deficiency, the test looks for elevated levels of medium-chain acylcarnitines, indicating that fats are not being broken down properly.
A positive screening result does not confirm the diagnosis but indicates that further investigation is needed. Families are contacted for follow-up testing, which includes more detailed blood and urine analyses and genetic testing to identify mutations in the ACADM gene. This early detection allows management to begin promptly.
Symptoms and Metabolic Crisis Triggers
If MCAD deficiency is not managed, individuals are at risk of a metabolic crisis from low blood sugar (hypoglycemia). The initial signs include lethargy, where an infant may be unusually sleepy or difficult to wake. Other symptoms are vomiting, poor appetite, and sweating.
As the crisis progresses, more severe symptoms can develop, including poor muscle tone, an enlarged liver, and seizures. These signs reflect a widespread energy deficit affecting the brain, liver, and muscles. If not treated immediately, a metabolic crisis can lead to a coma and can be fatal.
The primary trigger for a metabolic crisis is prolonged fasting. For an infant, this could mean sleeping through a feeding, while in older children and adults, it could be skipping meals. Common illnesses are also triggers because they can decrease appetite while increasing the body’s energy demands.
Daily Management and Treatment Protocols
The foundation of managing MCAD deficiency is the strict avoidance of fasting to prevent the body from needing to access its fat stores. For infants, this means a schedule of frequent feedings, including overnight. As children grow, this evolves into a routine of regular meals and planned snacks.
A specialized diet is recommended, focusing on being high in carbohydrates and low in fat. This ensures a steady supply of glucose, the body’s preferred energy source. The dietary plan is developed and monitored by a metabolic specialist and a dietitian.
An emergency plan for times of illness is necessary. When a person with MCAD deficiency is sick and unable to eat, they require immediate medical attention, which involves hospitalization for intravenous (IV) fluids containing glucose. Some individuals may also be prescribed L-carnitine supplements, which can help remove harmful substances that build up.
Prognosis and Lifelong Health
With a diagnosis from newborn screening and lifelong management, the prognosis for individuals with MCAD deficiency is excellent. Early and consistent treatment allows for normal growth and development. Intelligence and cognitive function are expected to be unaffected when metabolic crises are prevented.
Individuals with well-managed MCAD deficiency can expect to live a full and healthy life, as the condition does not limit life expectancy. Adherence to the dietary plan and management protocols is a lifelong necessity.
This ongoing awareness is important during times of increased metabolic stress. Events such as surgery, significant illness, or excessive alcohol consumption require careful planning with medical professionals. For females, pregnancy also requires specialized management.