MCAD Deficiency

Introduction

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited disorder of fat metabolism that prevents the body from making enough energy when a person is stressed, ill or fasting. When the body has used up all of the sugars its stores from food, it turns to fats to make energy. In each cell in the body, energy is made as fats are broken down in the mitochondria, the “powerhouses of the cell.” In MCAD, one of the steps in the breakdown of fats is missing or reduced.  MCAD is the most common of the fatty acid oxidation disorders.

Signs and symptoms

Today in the United States, MCAD deficiency is typically identified in the first few days of life through newborn screening. This involves collection of a blood spot from the infant’s heel that is used for special testing. Before newborn screening, children with MCAD deficiency usually showed signs and symptoms of the condition, sometimes multiple times, during the first two years of life. These could include vomiting, enlarged liver (hepatomegaly), low blood sugar and low ketones (hypoketotic hypoglycemia), and lethargy (lack of energy). In some cases, these episodes worsened over time, leading to to coma or seizures after seemingly mild illnesses such as a viral illness or ear infection. Before newborn screening about 25% first episodes were fatal, and were often grouped into Sudden Infant Death Syndrome.

As they get older, children usually become less prone to serious episodes. A few individuals with MCAD deficiency who were born before newborn screening may have mild symptoms of the disorder in adolescence or adulthood.

Diagnosis

As noted, most MCAD deficiency patients are identified through newborn screening.  These infants are immediately referred to a physician who specializes in care of patients who have metabolic disorders. There, they have testing to confirm the diagnosis, and then immediate start of treatment. This testing may include beiochemical testing called an acylcarnitine profile , and DNA testing to look for the genetic changes that caused the condition.

If there is a family history of MCAD deficiency or if the parents are known to carry genetic changes that cause MCAD deficiency, prenatal diagnosis can be done during pregnancy using cells obtained from the amniotic fluid or during chorionic villus sampling (CVS). If an ill child has not been screened for MCAD as a newborn, diagnostic testing may involve analysis of specific fats called acylcarnitines, levels of free carnitine in the blood, and medium carbon-chain-length fats in the urine.

Genetics

MCAD deficiency occurs when an individual inherits one change (mutation) in the  MCAD gene called ACADM from each parent.  The vast majority of patients have one copy of the common mutation that causes a change in the protein chain. In MCAD, 90% of the patients inherit this common mutation from at least one parent in combination with a second mutation, while approximately 70% of patients inherit this same mutation from both parents.

Genetic counseling can benefit affected individuals, as well as their families.

Treatment

Day-to-day management of MCAD deficiency consists of avoiding excessive fasting that can lead to a coma. Infants should only go without food for a few hours (depends on age).with overnight fasts of 8 hours allowed after 6 months of age. Children over 1 year of age can usually safely go without food for 12-18 hours. Home blood glucose monitoring is not useful because an episode can begin before hypoglycemia (low blood glucose) has occurred.

Although it is reasonable to modestly reduce dietary fat to < 30 % of daily calories because this fuel cannot be used efficiently in MCAD deficiency, patients appear to tolerate normal diets. Formulas containing medium-chain triglyceride oil should be avoided. MCAD patients tend to have low blood levels of carnitine, however the use of carnitine supplementation is controversial Some investigators suggest a supplement of 50 to 100 mg/day of oral carnitine, but its usefulness is unproven.

Medical treatment should be sought immediately if an infant or child cannot keep down formula or food, or there is loss of consciousness or severe confusion, as these are signs of dangerously low blood sugar. At the medical facility, intravenous glucose-containing fluids are given to address the hypoglycemia. Specific therapy for the mild hyperammonemia that may be present during acute illness is not usually required, however a study has recently been completed that used an ammonia-reducing medication in MCAD deficient patients. Recovery is usually complete within 12 to 24 hours except where serious injury to the brain has occurred.

Investigational Therapies

Currently there are no active programs to develop additional specific treatments or management for MCAD. However, new approaches may appear as products that are effective in treatment of the entire class of fatty acid oxidation disorders are developed.

Information on current clinical trials is posted at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

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