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
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
- 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).
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.
Ozand PT, Rashed M, Millington DS, et al: Ethylmalonic aciduria: an organic acidemia with
CNS involvement and vasculopathy. Brain Dev 16 (Suppl);12, 1994.
Slukvin II, Salamat MS, Chandra S: Morphologic studies of the placenta
and autopsy findings in neonatal-onset glutaric acidemia type II. Pediatr Dev Pathol