Glutaric Acidemia Type II (GA-II)

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, muscular hypotonia, sweaty odorous feet, and death often in the neonatal period.

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

• 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

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

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.

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

Neonatal GA-II is 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 (late-onset glutaric acidemia type II) 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). The ethylamonic adipicaciduria form is characterized by distinctive congenital malformations (e.g., 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.

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.

Periods of stress, such as surgery, may precipitate acute deterioration. Adequate hydration and prevention of hypoglycemia should be ensured perioperatively and acid-base status monitored during major surgery. In patients with pulmonary hypoplasia, ventilation may be difficult and pulmonary arterial pressure increased.

No agents specifically contraindicated. Neurologic status may warrant avoidance of drugs that can precipitate seizures, such as enflurane and meperidine.

Glutaric Acidemia Type I (GA-I): Progressive neurologic disorder caused by a genetically transmitted inborn error of metabolism of glutaric acid.