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Glutaric Acidemia Type I
Monday, 06 September 2004
Monday, 29 November 2004
Glutaricaciduria I, GA-I, Glutaryl-CoA Dehydrogenase deficiency

What

Glutaric academia type I is an inborn error of metabolism that results from a deficiency of a mitochondrial enzyme named Glutaryl-CoA dehydrogenase. When this enzyme is missing, or not fully active, certain amino acids from the diet cannot be properly processed in the body. This results in a build-up of the amino acids named lysine, hydroxylysine, and tryptophan. These substances are toxic to the brain, specifically to a part of the brain named the basal ganglia. The basal ganglia play a role in control of movement.

Who

Males and females are equally affected by this disorder. In certain populations, such as Old Order Amish, Canadian Ojibway, and people of Swedish descent, rates of the disease are higher. Estimates suggest that 10% of this Amish population is carriers of a genetic change that causes this disorder. This condition is very rare, affecting approximately 1 out of every 30,000 births.

Signs and Symptoms

There can be a great degree of variability of symptoms in people affected with this disorder. Some will have very minimal symptoms while others will be severely affected. This variability is, in part, due to the amount of function of the enzyme Glutaryl-CoA dehydrogenase. Children, even those who may appear healthy at birth, are at highest risk for worsening of symptoms at times of infection or other illness. Common signs and symptoms of this disorder include: 1. Macrocephaly (large head) at birth 2. Seizures 3. Hypotonia (decreased muscle tone so that the child may appear floppy) 4. Dystonia (repetitive uncontrolled muscle movement and abnormal posturing) 5. Choreoathetosis (slow jerking movements of the arms and legs) 6. Loss of head control, opisthotonus (muscle spasms leading to position in which the head and the heels bend backwards) 7. Rigidity 8. Hypoglycemia (low blood sugar) There is usually no loss of intellectual function. At times of infection (flu, ear infection, fever, stomach virus) a metabolic crisis can occur and is characterized by symptoms of seizures, nausea and vomiting, metabolic acidosis (increase in total amount of acid in the body), hepatomegaly (enlarged liver) and coma. These are followed by incomplete recovery and further central nervous system damage (for instance, further loss of motor control).

Possible Causes

The deficiency of Glutaryl-CoA dehydrogenase results from a change in a gene located on chromosome 19. Glutaric academia type I is inherited in an autosomal recessive manner. This means that both parents must carry an abnormal copy of the gene and both parents must pass this changed (mutated) copy to the child. There is a 1 in 4 chance (25%) in each pregnancy of having an affected child if both parents carry a changed copy of this gene. Carriers themselves do not have the disease because they still have one functioning copy of the gene.

Diagnosis

At birth, this condition is sometimes diagnosed through newborn screening. Several States include the test for GA-I in their newborn screening programs, though most States do not yet do this. The newborn screening test evaluates for a specific marker in the blood. To confirm the diagnosis, a urine test can be done to find the increased level of glutaric acid found with this disorder. It is also possible to test for the level of function of the enzyme. It is possible to do prenatal diagnosis through amniocentesis or chorionic villi sampling.

Treatment

Without treatment, most children will eventually develop neurological symptoms. Therefore, it is best to start treatment as early as possible in order to ensure the best possible outcome for the child. The main form of treatment involves dietary changes to avoid the amino acids lysine and tryptophan. Infants are usually fed a special formula and older children are placed on a low-protein diet. Because this diet can be difficult to maintain a dietician is usually involved in the care of the patient. After age 6, risk of deterioration is reduced and it is sometimes possible to increase the total protein intake. Sometimes dietary restrictions alone are not enough to manage this disorder and there may be a need to supplement with the medications carnitine and riboflavin. Carnitine is a compound that facilitates the excretion of glutaric acid. Riboflavin helps glutaryl CoA dehydrogenase work and may aid the function of the small amount of enzyme that is still present. At times of crisis, IV fluids, insulin, glucose, and bicarbonate may be necessary.

Prognosis

The prognosis for each patient is difficult to predict, especially early in life, since there is a wide range of symptoms associated with this disorder. It is very important to maintain the special diet for this disorder, to try to avoid infections, and to quickly respond to any metabolic crisis. Children with this disorder usually have normal intelligence and can do very well in school.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

International Organization of Glutaric Acidemia
Offers support, online message board, and information including useful links.

Organic Acidemia Association
Website has further information, support groups and further weblinks. Specifically, there is a personal story about a girl with GA1.

http://www.oaanews.org/article.asp?article=251

CLIMB (Children Living with Inherited Metabolic Diseases)
Website with family and children services, support groups, many topics to choose.

Google Search for Glutaric Acidemia Type I

References and Sources

Glutaric Acidemia Type I www.savebabies.org/diseasedescriptions/ga1.php OMIM: Glutaricacidemia I www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=231670 Glutaric Acidemia I (GA-I). web1.tch.harvard.edu/newenglandconsortium/NBS/descriptions/GAI.html Glutaric Acidemia Type I www.formydiet.com/Information/Doc.aspx?a=83 Rohr, R. Glutaric Acidemia Type I: Dietary Management www.meadjohnson.com/metabolics/glutaricacidemia1.html Strauss KA, Pufffenberger EG, Robinson DL, Morton DH (2003). Type I Glutaric Aciduria, Part 1: Natural History of 77 Patients. Am. Jour. of Medical Genetics Part C (Semin. Med. Gen.) 121C:38-52 www.clinicforspecialchildren.org/format/Strauss_2003a.pdf