Short-chain acyl-CoA dehydrogenase deficiency, or SCADD, is a rare inherited condition that affects how the body processes certain fats. It belongs to a group of metabolic disorders known as fatty acid oxidation disorders. In individuals with SCADD, the body’s ability to convert specific fats into energy is impaired. This process is especially important during periods without food, such as overnight fasting or during an illness. Many infants with this condition are now identified shortly after birth through routine newborn screening programs, often before any symptoms develop.
Genetic and Metabolic Causes
SCADD is caused by mutations in the ACADS gene. This gene contains the instructions for producing an enzyme called short-chain acyl-CoA dehydrogenase. The condition is inherited in an autosomal recessive pattern, meaning an individual must inherit one non-working copy of the ACADS gene from each parent to be affected. Individuals who inherit only one copy are considered carriers and do not experience any health effects related to the condition.
The short-chain acyl-CoA dehydrogenase enzyme plays a specific part in metabolism. It is responsible for the initial step in breaking down a group of fats called short-chain fatty acids. These fatty acids are an energy source for the body, particularly for the heart and muscles. During periods of fasting or illness when the body’s primary sugar stores are low, these fats become a necessary fuel for the liver and other tissues.
When mutations in the ACADS gene lead to a deficient or non-functional enzyme, the breakdown of short-chain fatty acids is blocked. This prevents the body from effectively converting these fats into usable energy. Consequently, the short-chain fatty acids and other substances can accumulate in the body’s tissues. The inability to access this energy pathway is most impactful when the body is under stress and in need of alternative fuel sources.
Symptoms and Diagnosis
The presentation of SCADD varies widely, and a large majority of those diagnosed never develop any related health problems. When symptoms do occur, they often appear in infancy or early childhood and may be triggered by stressors like a viral infection or fasting. Potential signs can include vomiting, low blood sugar (hypoglycemia), lethargy, and poor feeding in infants. Some children may also exhibit poor muscle tone (hypotonia), seizures, or developmental delays.
The initial indication of the condition is typically a result from a standard newborn screening panel. The test uses tandem mass spectrometry to analyze a small blood sample and may show an elevated level of a substance called C4 acylcarnitine, which suggests a problem with fatty acid breakdown.
An abnormal newborn screen is not a final diagnosis and requires further investigation. Confirmatory testing is performed to verify the presence of SCADD. These follow-up tests include a urine analysis to look for elevated levels of ethylmalonic acid. The most definitive diagnostic step is genetic testing, which analyzes the ACADS gene to identify the specific mutations.
Treatment and Management
The primary management strategy for SCADD is centered on dietary habits and proactive care during illness. The main goal is to prevent the body from relying heavily on fat metabolism for energy. This is achieved by avoiding prolonged periods of fasting. For infants and young children, this means ensuring they have regular feedings.
For most individuals with SCADD, particularly those who are asymptomatic, no specialized daily medications or restrictive diets are required. The focus remains on maintaining a steady intake of calories to meet the body’s energy demands through standard food sources. This approach helps prevent the metabolic stress that could potentially trigger symptoms.
A “sick day plan” is an important component of management. When a person with SCADD has an illness, such as a fever or a stomach virus that causes vomiting or poor appetite, it is important to ensure they receive adequate fluids and calories. Providing simple carbohydrates, like juices or sugary drinks, can help prevent blood sugar from dropping too low. Families are advised when to contact their medical provider for guidance or treatment, which may include intravenous fluids if they are unable to eat or drink.
Prognosis and Clinical Significance
For the vast majority of individuals identified with SCADD, the long-term outlook is excellent. Most people diagnosed with the condition, especially the large asymptomatic group found through newborn screening, are expected to have normal growth and development. With simple management strategies focused on avoiding fasting, they can lead full and healthy lives.
The widespread use of expanded newborn screening has led to the identification of many more infants with the biochemical markers for SCADD than were previously recognized. Because so many of these individuals never show any signs of illness, a discussion has emerged within the medical community regarding the condition’s clinical significance. This has prompted some experts to question whether SCADD should always be classified as a disease.
This debate centers on whether SCADD in an asymptomatic person is better described as a benign biochemical variation rather than a true disorder. The perspective suggests that for many, the genetic trait may not cause harm or lead to health problems. This context is helpful for families, as it can alleviate some of the anxiety that comes with a genetic diagnosis by framing it as a manageable trait with a positive prognosis.