An 8-year-old boy is brought to the emergency department due to vomiting and lethargy. The patient had been on an overnight hiking trip with his family. During the trip, the family lost their food pack while canoeing and had to hike back to their car. The child became weak and was carried for the last mile. None of the family has eaten for approximately 24 hours. On examination, the patient appears listless. Mild hepatomegaly is noted. Laboratory results are as follows: The patient begins seizing shortly after arriving at the emergency department. Which of the following enzymes is most likely deficient in this patient?

Question

An 8-year-old boy is brought to the emergency department due to vomiting and lethargy.  The patient had been on an overnight hiking trip with his family.  During the trip, the family lost their food pack while canoeing and had to hike back to their car.  The child became weak and was carried for the last mile.  None of the family has eaten for approximately 24 hours.  On examination, the patient appears listless.  Mild hepatomegaly is noted.  Laboratory results are as follows:  The patient begins seizing shortly after arriving at the emergency department.  Which of the following enzymes is most likely deficient in this patient?

Quizplus · Accepted Answer

11ec160b_3695_2cff_9249_bf2f6009a08b_MD0001_00 This patient developed hypoketotic hypoglycemia after fasting, which is consistent with a defect in fatty acid beta-oxidation in the mitochondria. Beta-oxidation of fatty acids yields FADH₂ and NADH for ATP production and generates acetyl-CoA for use in the citric acid cycle or ketone body production. Ketone bodies are an important energy source during periods of fasting; adults generally require more than 1-2 days of fasting before ketone use becomes substantial, whereas children have limited glucose reserves and begin using ketone bodies after as little as 8-10 hours. Impaired beta-oxidation can be caused by a variety of enzymatic defects, the most common of which is medium chain acyl-CoA dehydrogenase deficiency. Affected individuals may remain asymptomatic for long periods until they experience a significant fast, during which they are unable to oxidize fatty acids to maintain glucose and ketone body production. Classic manifestations include hypoketotic hypoglycemia (eg, undetectable acetoacetate level), mild hepatomegaly, and liver dysfunction. Because the resulting metabolic crisis can have severe consequences (eg, seizures, sudden infant death), fatty acid oxidation disorders are part of standard newborn screening. Treatment of acyl-CoA dehydrogenase deficiency consists of prevention of fat catabolism. This means avoiding prolonged fasting as well as promptly supplying glucose during periods of illness. (Choice A) Acetyl-CoA carboxylase is the rate-limiting enzyme that catalyzes the first step in fatty acid synthesis. Acetyl-CoA carboxylase is normally suppressed during prolonged fasting. (Choices B, D, and E) Acid alpha-glucosidase, glucose 6-phosphatase, and glycogen phosphorylase are involved in glycogenolysis. Deficiency of any of these enzymes can lead to glycogen storage disease. However, patients with glycogen storage disease have normal fatty acid oxidation and produce ketones during periods of fasting. Educational objective: Impaired beta-oxidation of fatty acids causes hypoglycemia after prolonged fasting and insufficient levels of ketone bodies. Acyl-CoA dehydrogenase catalyzes the first step in the beta-oxidation pathway and is the most commonly deficient enzyme. __________ References: Newborn screening for medium chain acyl CoA dehydrogenase deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/18838415) Ketone body transport in the human neonate and infant. (http://www.ncbi.nlm.nih.gov/pubmed/3944260)

An 8-Year-Old Boy Is Brought to the Emergency Department Due