Glutaric Aciduria: What Happens When Your Body Can't Process Proteins?

Glutaric aciduria is an inherited metabolic disorder that involves the body being unable to process different proteins. Those with this disorder have inefficient levels of an enzyme that breaks down the amino acids tryptophan, hydroxylysine and lysine.  These amino acids are the building blocks of protein and extreme levels in the body can accumulate and cause brain damage.

Glutaric aciduria can cause damage to the basal ganglia in the brain and it may result in intellectual disabilities. The severity of the disorder can vary widely, some people are only moderately affected and others will have profound problems. In most situations, signs and symptoms will show up during infancy or early childhood. However, in a small number of people, it first becomes apparent during adolescence or adulthood.

Different Types Of Glutaric Aciduria

There are three different types of glutaric aciduria, and each one has its own unique symptoms.

Type I:

• The first thing most will notice with GA-1 is a baby having microencephalic macrocephaly (small brain in a large head)
• Failing to thrive, poor muscle development and low blood sugar
• It may cause brain damage in the basal ganglia
• Gastroesophageal problems
• Skeletal issues
• Respiratory complications
• Cerebral palsy
• Cardiac failure
• Seizures
• Lethargy

Type II:

• Hypoglycemia
• Respiratory distress
• Musty breath (often described as smelling like sweaty feet)
• Muscle hypotonia
• Liver damage
• Renal and/or cardiac problems
• Proximal myopathy (weakness)

Type III:

• Chromosomal abnormalities
• Bowel disorders
• Thyroid dysfunction
• Failure to thrive

How Rare Is Gluratic Aciduria?

Type I glutaric aciduria is extremely rare. There have been limited studies of the disorder that suggest it occurs in one in 40,000 Caucasian births. However, a study in Sweden estimated the incidence of the disorder around one in 30,000 births in its population. It’s more common in genetically close cultures such as the Ojibway Indian population in Canada or in the Amish in the United States, where it can happen as much as 1 in 300 births. There is a tendency to misdiagnose this disorder, which makes it difficult to get an accurate figure of the frequency.

How Is Glutaric Aciduria Diagnosed?

Glutaric aciduria Type 1 is a rare disease that may lead to acute brain damage in early childhood. The brain damage it causes can result in a severe dystonic disorder which is very similar to cerebral palsy. Diagnosing the disease will be dependent upon the recognition of relatively non-specific physical findings. A doctor may order a blood or urine test to check a person’s levels of glutarylcarnitine, which if high, would be an indication of the disease.

Test Results: Positive Or Negative?

If a person is tested for glutaric aciduria and a gene mutation is identified, it’s important to speak to a physician or genetic specialist about the implications. A negative test result will reduce, but not eliminate, the likelihood of an individual carrying a genetic mutation. The chances of a person being a carrier of the gene will be influenced by family history, medical symptoms and other relevant test results.

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Can It Be Prevented?

It’s entirely possible to screen a newborn baby for Type I glutaric aciduria using blood from a heel-prick test and running it through a tandem-mass-spectrometer. The technique is being used in high risk populations like the Amish. Using this method of testing can help to minimize the amount of brain damage the disease causes, by early dietary manipulation and supplements. Because this disease is so uncommon, routine population-based testing is not currently used.

Treatment For Glutaric Aciduria

As with many other types of metabolic disorders, glutaric aciduria causes many different symptoms. One way of treating the disease is through the correction of secondary carnitine depletion. Whole-blood carnitine levels can be raised through a person receiving oral supplementation. Through regular intravenous infusions of carnitine, clinical improvement was witnessed and it improved growth, muscle strength and decreased an individual’s reliance on medical foods with high protein content.

Having tryptophan in the body is crucial for the proper synthesis of serotonin in the brain. The process of protein synthesis elicited by amino acids, leads the circulating amino acids in the blood, to be converted into proteins. A doctor may recommend taking tryptophan formulas such as XLys, XTrp Analago and Glutarex 1, which are designed to provide amino acids in order to prevent protein malnutrition.

Other ways of treating glutaric aciduria is restring the amount of lysine in the diet. However, patients who have suffered an encephalopathic crisis may be excluded. Vegetarian diets for younger children and breastfeeding infants are common ways to restrict the amount of protein in the diet without compromising the transportation of tryptophan to the brain.

Prognosis For Glutaric Aciduria

Generally, it can be very hard to diagnose glutaric aciduria early, because it is hampered by a lack of clinical or pathognomic signs and symptoms before an encephalopathic crisis. According to US Library of Medicine National Institutes of Health, 75 percent of infants with the disorder have a large head and smaller brain. Many hospitals now include a GA-1 test as a part of disease panel for newborn screening.

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When glutaric academia is untreated, people will characteristically develop dystonia that is secondary to striatal injury during early childhood. This results in increased morbidity and mortality rates. In individuals who receive early diagnosis during infancy, treatment can begin sooner and the damage to the brain may be lessened.

GA-1 is often misdiagnosed but it may be mistaken for abuse because of the appearance a child may have. Prenatal diagnosis of the disease can be made by the presence of glutaric acid in the amniotic fluid. Timely diagnosis and starting early treatment is extremely crucial, because it is likely to result in a better outcome for the child. However, even when treatment is provided, 25 to 35 percent of children with GA-1 are going to develop some level of motor and intellectual impairment.

If you have a child diagnosed with glutaric aciduria the best thing you can do is educate yourself about the disease. It’s possible to find resources online and consulting with a genetic counselor and a medical specialist, can provide you with a wealth of information that will prove vital in the care and outcome your child faces.