Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a rare inherited metabolic disorder. It interferes with the body’s ability to process certain types of fats, specifically short-chain fatty acids.
What is SCAD Deficiency
SCAD stands for Short-Chain Acyl-CoA Dehydrogenase, an enzyme found in cell mitochondria. This enzyme plays a role in the initial step of fatty acid beta-oxidation, a process that breaks down fats into energy. The SCAD enzyme helps break down short-chain fatty acids for energy, especially during fasting or illness.
When the SCAD enzyme is deficient due to mutations in the ACADS gene, short-chain fatty acids are not properly metabolized. This leads to an accumulation of incompletely broken down fatty acids and other potentially harmful substances in the body, such as butyrylcarnitine and ethylmalonic acid. These elevated levels can disrupt normal cellular function. SCAD deficiency is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the mutated ACADS gene, one from each parent, to develop the condition.
Identifying Symptoms
The symptoms associated with SCAD deficiency can vary significantly in severity and when they first appear. Many individuals identified with SCAD deficiency, particularly through newborn screening, remain without symptoms. When symptoms do occur, they often manifest during times of metabolic stress, such as prolonged fasting or illness.
Common symptoms in affected individuals may include feeding difficulties, vomiting, and a general lack of energy or lethargy. Poor growth and failure to gain weight at the expected rate are also observed. In some cases, more pronounced issues can arise, such as muscle weakness, poor muscle tone (hypotonia), and developmental delays affecting milestones like sitting, walking, or speech. Hypoglycemia, or low blood sugar, is another possible symptom, and in severe instances, seizures may occur.
Diagnosis and Treatment Approaches
SCAD deficiency is often identified through newborn screening programs, which are designed to detect metabolic disorders shortly after birth. These screenings typically use tandem mass spectrometry to measure levels of certain substances in a blood sample, such as elevated butyrylcarnitine (C4) concentrations. If initial screening results suggest SCAD deficiency, further confirmatory tests are performed.
Confirmatory tests include urine organic acid analysis, which can show increased levels of ethylmalonic acid, and blood acylcarnitine profiles to further evaluate fatty acid metabolites. Genetic testing for mutations in the ACADS gene provides a definitive diagnosis by identifying the specific genetic changes causing the enzyme deficiency.
The primary treatment approach for SCAD deficiency focuses on dietary management to prevent the accumulation of harmful metabolites. This involves avoiding prolonged fasting by ensuring frequent meals and snacks. For some individuals, a low-fat diet may be recommended to reduce the intake of short-chain fatty acids that the body struggles to process. In specific situations, carnitine supplementation may be prescribed to help the body remove harmful substances by aiding in the transport and elimination of fatty acid metabolites. Riboflavin (Vitamin B2) supplements may also be advised in certain cases.
Long-Term Outlook
The long-term outlook for individuals with SCAD deficiency varies, but with early diagnosis and consistent management, many can lead healthy lives with minimal or no symptoms. Adherence to dietary recommendations and any prescribed supplements is important for managing the condition and preventing potential metabolic crises.
Ongoing monitoring by a metabolic specialist is typically recommended to assess growth, development, and nutritional status. This regular follow-up helps to adjust treatment as needed and address any emerging concerns. While some individuals may experience learning delays, muscle weakness, or liver issues, particularly if symptoms were present before diagnosis, the overall prognosis is generally favorable for those who receive early and consistent care.