Glutaric Acidemia Type I
Robert Tomaino, Medical Writer
Glutaric acidemias (GA) are rare inborn errors of metabolism marked by the abnormal accumulation of glutaric acids and other chemicals in the blood and tissues of the body. There are two forms of glutaric acidemia: GA type I and GA type II. Glutaric acidemias are classified as organic acidemias. GA type II is further classified as a fatty acid oxidation disorder.
GA type I:
Glutaric aciduria type I
Glutaric acidemia type I is a genetic disorder that results from a mutation of a gene located on chromosome 19. Mutations of this gene result in deficiency of the enzyme glutaryl-CoA dehydrogenase, which is needed to metabolize (breakdown) certain amino acids, specifically lysine, hydroxylysine and tryptophan. Failure to breakdown these amino acids results in the accumulation of glutaric acids and other chemicals in the body.
The genetic mutations associated with glutaric acidemias are inherited in an autosomal recessive manner. The symptoms of glutaric acidemias result from the accumulation of glutaric acids and other chemicals in the blood and tissues of the body. Accumulation of these chemicals has toxic effects on various organ systems of the body.
The specific symptoms of glutaric acidemia type I differ from one infant to another. Some may develop life-threatening complications early in life; others may remain relatively stable. Some children develop a variety of neurological symptoms; others do not develop any. Intellect is usually unaffected.
Most infants with GA I may develop normally for several months to four years. However, at some point during this period, rapid onset of symptoms often occurs, usually following a viral respiratory or gastrointestinal illness. These symptoms include:
Symptoms may progress to cause enlargement of the liver (hepatomegaly), seizures, motor delays, and coma. After the age of five, symptoms often remain stable. Before the onset of neurological symptoms, some infants may be lethargic, irritable and jittery. Some infants may also have macrocephaly, a condition of increased head circumference.
- Nausea and vomiting
- Dystonia - a group a movement disorders characterized by muscle contractions; repetitive, uncontrolled movements; and abnormal postures
- Hypotonia - decreased muscle tonicity
- Choreoathetosis - uncontrolled, slow, writhing or jerking movements of the arms and legs
- Opisthotonus - muscle spasms where the head and heels bend backward
- Dyskinesia - impairment of voluntary movements (e.g., tics or spasms)
- Failure to thrive
Many infants with glutaric acidemia may be diagnosed through newborn screening (however, this is not offered in all 50 states, Supplemental Newborn Screening should be done), a process in which blood is taken from the heels of an infant. Several tests are performed on the blood samples that may detect glutaric acidemia. For example, enzyme assay may detect decreased activity certain enzymes in certain white blood cells (leukocytes) and connective tissue cells (fibroblasts). Analysis of urine samples may reveal elevated levels of glutaric and other acids that may be indicative of glutaric acidemia.
Prenatal diagnosis of glutaric acidemia is possible through amniocentesis. Amniocentesis is a common prenatal procedure in which a small amount of amniotic fluid (the protective fluid that surrounds a fetus) is removed and studied. Excess glutaric acid in amniotic fluid is indicative of glutaric acidemia. Enzyme assay of amniotic fluid cells (amniocytes) may indicate GA type I. GA type I may also be diagnosed prenatally by chorionic villus sampling (CVS), a procedure in which tissue samples are obtained from the placenta.
Without treatment, children with GA type I eventually develop neurological symptoms. Most cases are treated by a strict, protein-deficient diet. However, diet alone has been unsatisfactory in treating most affected children. Supplemental treatment with L-carnitine and riboflavin is usually administered in addition to a restricted diet. During acute illness, children may be treated with fluids, electrolytes, and glucose. Many children with GA type I who receive such treatment do not develop neurological symptoms.
Glutaric acidemias are rare, metabolic disorders that are under-diagnosed. GA type I is often misdiagnosed as cerebral palsy. Prompt diagnosis and treatment is essential for infants with these disorders. However, significant symptoms may still occur despite treatment and proper diet, especially in severe forms. Mild forms of glutaric acidemia respond to a protein restricted diet and supplemental treatment.
Robert Tomaino is currently a freelance writer living in Danbury, CT. He graduated from the University of Richmond in 1994 with a degree in communications and journalism. Mr. Tomaino spent five years at the National Organization for Rare Disorders (NORD) where he started as a writer and became managing editor of the Information Services department. His responsibilities included writing and updating new and existing reports for NORD’s rare disease database, researching textbooks and medical databases for information on rare disorders, and developing working relationships with physicians across the country who are the leading experts concerning specific rare disorders. Mr. Tomaino also supervised a freelance writing team at NORD. After NORD, Mr. Tomaino worked at Enterprise Interactive, a business consulting firm, where he developed story ideas and researched various online sources for background information necessary to create news articles on topics related to e-commerce solutions, travel, and the Internet’s impact on business.
Review Date: 5/24/2004
Reviewed By: Bibina J. Varughese, R.D., Pediatric Metabolic Nutritionist, Institute for Genetic Medicine, Saint Peter's Univ Hospital, New Brunswick, NJ.
Bibina Varughese, RD
Bibina J. Varughese is a Registered Dietitian with 12 years experience in Nutrition. Bibina graduated from The College of St. Elizabeth in Convent Station, NJ with her Bachelors degree in Home Economics.
Bibina has worked in the Metabolic field for 5 1/2 years at Saint Peter's University Hospital (SPUH), Institute for Genetic Medicine in NJ. Here she managed the diets of children and adults with Metabolic and Genetic disorders such as PKU, MSUD, Galactosemia, FOD, etc. At the metabolic center, Bibina has worked closely with families in providing diet education, obtaining authorizations for approval through insurance companies for special food and formula coverage, and providing nutritional (Metabolic) education to the State WIC nutritionist.
Bibina resigned from the Metabolic center, a full time position, as the metabolic dietitian and was working part time as a clinical dietitian at SPUH for the Department of Food and Nutrition. In this position, her main duty is to provide therapeutic nutritional education to patients with Diabetes, Heart Disease, Cancer, Prenatal, and others. However at the present time she has returned to the Metabolic Center at the Institute for Genetic Medicine for an interim period of time.
Prior to joining St. Peter's, she worked at Jersey Shore University Hospital in NJ. Her primary role was providing nutritional education to pediatric and cancer patients.
Bibina is a member of the American Dietetic Association and the New Jersey Dietetic Associations.