MCHAD/SCHAD Deficiency

Introduction

Medium/short chain L-3-hydroxyacyl-CoA dehydrogenase (M/SCHAD) deficiency is a rare inherited disorder of fat metabolism that prevents the body from making enough energy during stress, illness and fasting. When the body has used up its stores of sugars, it must turn to fats to make energy. In each cell in the body, this breakdown of fats is done in the mitochondria, the “powerhouses of the cell,” in a four-step process known as beta-oxidation.  M/SCHAD is a member of a protein family that performs the third step in the process. In addition, M/SCHAD has a different role inside the mitochondria as a part of the control of insulin secretion. Without M/SCHAD, too much insulin goes into the blood, causing low blood sugar levels. Loss of normal control of insulin levels is the most dangerous aspect of M/SCHAD deficiency.

Signs and symptoms

The symptoms of M/SCHAD deficiency include extreme sleepiness, irritability, poor appetite, and mood changes. Infants with M/SCHAD may also develop liver disease.

Without appropriate treatment, patients may have fever, diarrhea, vomiting, and low blood sugar, which can worsen to cause seizures and coma.  These symptoms usually appear the first time the child gets an illness and stops eating regularly. Without regular feedings, M/SCHAD deficient infants have too little blood sugar (glucose) to use for energy when facing minor stresses like an ear infection or diarrhea. They also have too much insulin in their blood, which further lowers blood sugar, plus they cannot use fat to make energy, so have 2 reasons to develop the symptoms listed above.

Diagnosis

While M/SCHAD deficiency is very rare and difficult to diagnose, many potential children are identified right after birth through newborn screening, before they can show symptoms. Once identified by newborn screening, infants will be sent to a physician to look for the combination of low blood sugar with high levels of insulin. Urine will be tested for the presence of specific fats and skin cell samples will be examined for reduced M/SCHAD activity. The final diagnosis depends on the identification of mutations in the gene for M/SCHAD.

Genetics

Everyone has two genes that make the M/SCHAD protein; this gene has two names –HADHSC or HADH. In children with M/SCHAD deficiency, both copies of the gene have changes/mutations. This causes either no protein or protein that does not work well to be made. The disorder is inherited, with one altered gene for M/SCHAD coming from each parent, although occasionally parents may carry two altered/mutant genes. In the parents, the one good HADHSC gene makes enough protein to keep the parents healthy. When both parents carry the mutation, there is a 25% chance in each pregnancy for the child to have M/SCHAD. There is also a 50% chance for the child to be a carrier, just like the parents, and, there is a 25% chance for the child to inherit two healthy genes.

Treatment

The goal of treating SCHAD deficiency is to avoid low blood sugar (hypoglycemia). Because M/SCHAD defects can lower blood sugar in two different ways, treatment can take two different approaches. First, the drug diazoxide is given to reduce insulin levels in the blood. Second, patients should avoid fasting and receive plenty of carbohydrates and sugars, since their cells can’t use fats for energy. If a M/SCHAD patient is sick, intravenous (IV) fluids with glucose solutions may be given to prevent blood sugar levels from dropping.

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