Glutaric acidemia type 1 (GA-1) is caused by a deficiency of glutaryl-CoA dehydrogenase which results in the accumulation of 3- hydroxyglutaric acid. It is an autosomal recessive inherited disorder that leads to the disruption of the lysine, hydroxylysine, and tryptophan metabolism.
Nutrition management involves:
- Restricting lysine and tryptophan rich diets
- Supplementation of L-carnitine, riboflavin, and pantothenic acid
- Lowering levels of 3-hydroxyglutaric acid and glutaric acid
There are two methods for nutrition management of GA-1 when the condition is chronic and when it becomes acute.
Nutrition management of chronic GA-1
Nutritional management of a GA-1 patients is the prompt treatment to the intercurrent illnesses which is a most critical component in the history of the dietary management.
Amino acids lysine and tryptophan are restricted in the diet for a patient with GA-1. Medical diets free of lysine and tryptophan provide varying amounts of essential amino acids, fat, carbohydrate, vitamins, and minerals as well as L-arginine used to meet protein goals.
Solid foods that are naturally low in protein (lysine) may be introduced when developmentally appropriate for the child and specialty low protein foods may be used to provide sufficient energy, and to add variety to the diet.
L-carnitine supplementation is also an integral component of management which is routinely provided to patients with GA-1 to reduce intramitochondrial glutaryl-CoA and provide extracellular release without the synthesis of glutaric acid and 3-hydroxyglutaric acid. This results in neurological improvement and reduced urinary glutaric acid excretion in one patient.
Nutrition management of acute GA-1
When GA-1 turns acute, the risk for neurological injury is highest during illnesses with reduced energy intake, fever, and associated catabolism. Overly aggressive treatment and mandatory hospital admission during any of these presentations can help prevent permanent neurological damage.
During an illness that is associated with catabolism, maintaining usual therapy (“well-day” diet) and supplementing L-carnitine is not sufficient to prevent an acute crisis; additional nonprotein energy sources must be provided.
Sick-day management includes reducing natural protein intake, continuing consumption of lysine- and tryptophan-free medical food, and providing extra sources of protein-free energy. The L-carnitine dose is often increased as well.
Routine assessments including anthropometrics, dietary intake, and physical findings.
Laboratory monitoring – diagnosis specific
- 3-hydroxyglutaric acid (urine)
- Glutaric acid (urine)
- Carnitine (total, free, esterified)
- Plasma amino acids, including: – Lysine – Arginine – Tryptophan
Monitoring plasma amino acids is necessary to ensure that concentrations of essential amino acids, lysine and tryptophan, are maintained within the normal range for the age.
Nutrition management of GA-1 presents a clinical challenge because the benefit of a lifelong lysine and tryptophan-restricted diet is not established.
Preventing acute metabolic crisis is the primary goal of treatment. Lysine-restricted, arginine-supplemented diets are believed to offer some benefits, perhaps by altering the flux of lysine and arginine across the blood-brain barrier.