Description of Disorders

Glutaric Acidemia II (GA2/MADD)

Glutaric Acidemia type-II is a very rare inherited order. GA2 is an autosomal recessive disorder, which means that both parents, who are carriers, carry a defective gene and when both of those defective genes combine, a child is born with the disorder. Each child has a 25% chance of inheriting the disorder. For parents who wish to know ahead of time, there are special prenatal tests that can be done to determine if their unborn child is affected by the disorder.

This disorder has also been called Multiple acyl CoA Dehydrogenase Deficiency (MADD). People with GA2 have an inactive enzyme (a protein in the body). There are two specific enzymes that may be associated with this disorder: Both of these enzymes have similar functions in the body, and individuals with GA2 may lack either one of them.

  1. Electron Transfer Flavoprotein (ETF)
  2. ETF-ubiquinone oxidoreductase (ETF:QO)

Both ETF and ETF:QO are found in many cells of the body, and play an important role in breaking down fats and proteins, and helping to produce energy. These are very important functions for the body to stay healthy. Because people with this disorder lack either of these enzymes, they can become very ill.

Symptoms
Unfortunately, some newborns that develop severe symptoms during the first days of life usually do not survive for more than a few weeks or months because they have the very severe form of the disorder, called Neonatal Glutaric Acidemia Type-II.

The information within this article discusses the less severe form of the disorder called Late Onset Glutaric Acidemia Type-II, whereby the age of onset can be extremely variable. It is important to note that each child will be affected by the disorder to different degrees, some more than others. Many children with this disorder may not display symptoms until they are several years old, perhaps not even until they are adults.

Clinical features may include acidosis, nonketotic hypoglycemia, and heart disease, and in milder cases, intermittent episodes of nausea and vomiting, lethargy, weakness, and liver enlargement. Often after a stress of some sort (i.e., virus, exercise), there may be periods of low blood sugar. This hypoglycemia can be very severe, and make your child feel weak, shaky, and dizzy.

Diagnosis
GA2 can be quite easy to recognize in the newborn with total deficiency of ETF or ETF:QO as shown by the abnormal pattern of organic acids in the urine. However, it's more difficult to make the diagnosis in children with incomplete defects because the clinical features in these patients may be episodic and quite varied, and because the urine organic acids may be abnormal (and then only slightly so) only when they are acutely ill.

Diagnosis is also complicated by the fact that similar urine organic acid changes may be seen in deficiency of riboflavin (i.e. vitamin B2), and when infants are fed formulas containing medium-chain triglycerides. Ill infants are often fed such formulas.

Increases in certain carnitine esters in blood can suggest GA2 in some of these children but, as with urine organic acids, might well be due to riboflavin deficiency. Studies on fibroblasts grown from a skin biopsy may be the best way to make the diagnosis because they are not influenced by nutrition. Labs across the country that test for GA2 may perform different tests to diagnose GA2 so you may want to have your physician inquire which method they use.

Treatment
The 'milder' or late onset GA2 is currently treated with a low fat, low protein, and high carbohydrate diet. This means that children with this disorder should eat foods with very little fat or protein in them, since their bodies lack the enzymes to break these elements down. Instead of fat and protein, they should eat lots of carbohydrates so they'll be sure to get enough calories for energy. Eating often is recommended to avoid fasting and possibly low blood sugar, which can trigger a metabolic crisis. A metabolic nutritionist should be able to assist you in developing a food plan that meets your child's needs. Also refer to our Nutritional Resources in the "Nutrition and Recipes" section of this website for low fat and low protein suggestions. Additionally, supplementation with riboflavin and L-carnitine has been recommended with the mild and late-onset form.

Having this disorder, or any disorder for that matter, is a family affair and the family plays an important role in the effective treatment of GA2. The other siblings, as well as the child with the disorder, should be taught early on about the special dietary considerations. Encourage the other children to help feed your child with GA2 so they become familiar with what foods are allowed and which foods should be limited. Explaining GA2 to everyone that will have contact with your child (i.e., relatives, teachers, babysitters), and what signs to look for to avoid a crisis, as well as having an Emergency Protocol sheet available to them, is important for all involved. There will inevitably be a time when an emergency situation occurs, so be prepared!

[This information was compiled from two sources: an FOD/GA2 parent who was given informational sheets on GA2 (author was not known by the parent) and from Dr Steve Goodman, who is co-Director of the University of Colorado Health Sciences Center, Biochemical Genetics Lab. If anyone believes informational corrections are needed for this article, please send them to Deb]