SCAD Deficiency

Introduction

Short chain acyl-CoA dehydrogenase (SCAD) deficiency is one of a group of inherited protein alterations that affect the mitochondria’s ability to generate cellular energy from fats during stress, illness and fasting. In children with SCAD deficiency, the first step in the final round of breaking down fats is reduced or missing. Fortunately, this loss of function toward the end of the process means that SCAD defect usually has less impact than fat oxidation disorders that occur earlier in the process.

Signs and symptoms

Most children and adults with SCAD mutations do not show any specific symptoms. Earlier reported clinical findings have included episodes of intermittent metabolic acidosis, coma from elevated blood ammonia (hyperammonemic coma), neonatal acidosis with elevated muscle tone (hyperreflexia), multicore muscle breakdown (myopathy), and muscle fat storage with failure to thrive, and poor muscle tone (hypotonia). Unlike other fat oxidation defects, SCAD deficiency does not cause low blood sugar (hypoglycemia) or low ketones (hypoketosis).

Diagnosis

Today, the majority of SCAD patients in the U.S. are identified right after birth by the expanded newborn screening program. A blood spot is obtained from the infant’s heel and sent to a laboratory for screening before the infant goes home from the birthing facility. The diagnosis involves an analysis of two fat products, butrylcarnitine and ethylmalonic acid, that tend to accumulate in blood and urine of infants with a SCAD deficiency. Because pure SCAD alterations are considered benign, many newborn screening programs no longer report infants with butrylcarnitine elevations, especially those with lesser changes. However, butrylcarnitine and ethylmalonic acid can accumulate in other metabolic defects besides SCAD. As a result, infants or children with symptoms of fat oxidation disorders, along with increased levels of these two metabolites may be referred for further study to rule out other metabolic syndromes.

 

Genetics

SCAD deficiency occurs when an individual inherits one mutation in the gene for SCAD (ACADS) from each parent. There are two common SCAD alterations that change the active protein but leave it with sufficient activity to function without causing illness. Some rare mutations cause more loss of protein function and more accumulation of butrylcarnitine and ethylmalonic acid, but still rarely cause illness. One rare mutation inherited with one of the common alterations usually results in an intermediate loss of activity.

Treatment

At present, SCAD deficiency is considered a benign condition with no characteristic symptoms that need to be treated.

Investigational Therapies

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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