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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.
- Electron Transfer Flavoprotein (ETF)
- 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]
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