Glutaric Acidemia Type II (GA-II)

At a glance

A progressive neurologic disorder caused by a genetically transmitted inborn error of metabolism in which the body cannot oxidize fatty acids. Typical clinical features include respiratory distress, heart failure, hypoglycemia, acidosis, muscular hypotonia, characteristic sweaty odorous feet, and death often in the neonatal period.

Synonyms

Glutaric Aciduria II; Multiple Acyl-CoA Dehydrogenase Deficiency (MADD); Electron Transfer Flavoprotein (ETF) Deficiency; ETF-Ubiquinone Oxidoreductase (ETF:QO) Deficiency.

Classification

• Glutaric Aciduria Type IIA: Neonatal form of glutaric aciduria II

• Glutaric Aciduria Type IIB: Adult form of glutaric aciduria II. Also known as the late onset form of glutaric aciduria

• Glutaric Aciduria Type IIC: Ethylamonic adipicaciduria

Genetic inheritance

X-linked (neonatal form) or autosomal recessive (mild or “adult” form). Affects males and females equally.

Pathophysiology

Two enzyme deficiencies may be associated with this disorder: electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETF:QO), which play major roles in the catabolism of fatty acids and proteins. On the molecular level, these patients have mutations in electron transfer flavoprotein. These mutations disable the electron transport chain and metabolism of proteins and fats. Proteins and fats are metabolized incompletely and it can lead to profound nonanion gap metabolic acidosis.

Diagnosis

Typical abnormal pattern of organic acids in the urine of neonates with GA-II (far less typical in milder forms).

Clinical aspects

There are three types that consists of:

• Neonatal GA-II: Characterized by severe hypoglycemia, metabolic acidosis, hypotonia, heart disease, hepatomegaly, and, frequently, an odor of “sweaty feet.” Often fatal during the first week of life.

• Milder Forms: Consist of late-onset glutaric acidemia Type II. They do not display congenital anomalies, and symptoms usually consist of intermittent episodes of nausea and vomiting, lethargy, weakness, and liver enlargement. Acute episodes of hypoglycemia may be extremely severe, often after infection, exercise, or any form of stress (including surgery).

• Ethylamonic Adipicaciduria Form: Characterized by distinctive congenital malformations (eg, pulmonary hypoplasia, facial dysmorphism) and severe hypoglycemia. Vascular lesions of the skin (petechiae, ecchymoses), acrocyanosis, and retinal lesions have been described. Prolonged diarrhea may occur. Respiratory failure may precede death.

Precautions before anesthesia

Maintain adequate hydration and avoid fasting whenever possible (diet high in carbohydrates, low in protein and fat). Prevent hypoglycemia (glucose infusion). Check acid-base status. Assess neurologic status. Consider prophylactic antibiotics. Diagnosis of GAII is by examining urine for organic acids. Treatment of the disorder includes avoidance of fasting, protein restriction, and vitamin supplementation. The goal is to replenish CoA supply, prevent neurological consequences, and detoxification of organic acids. Even minor illness requires aggressive maintenance of caloric intake either orally or via central line.

Anesthetic considerations

Periods of ...