Question

Upon presentation: An 18-month-old female arrives by ambulance at the emergency department. The paramedics report that there was no known history of any recent trauma, and no known fever, vomiting, or other unusual behavior. There were no known ingestions or medications in the household. There was no evidence of trauma. Interview and History: At 9 PM the previous night, Ella was described by her mother as appearing more quiet than usual. They had spent the day traveling from the grandmother's house and Ella had been carsick so had not eaten very much during the day. When they got home, Ella had some water and went to bed. Ella slept longer than usual and was found unresponsive by her mother at 9 AM. At this time her mother called 911. Follow-up tests: 1) Blood glucose: 23 mg/dL (normal range 90 – 125 mg/dL) 2) Repeat blood glucose: 50 mg/dL following administration of glucagon 3) Urinary acids: Markedly elevated levels of glutaric, ethylmalonic, and dicarboxylic acids; ketones absent 4) Serum free fatty acids: 0.84mmol/L (normal range: 0.00-0.72 mmol/L) Treatment: She was transferred to the pediatric intensive care unit and remained comatose for 16 hours. Blood glucose levels remained stable with a continuous infusion of dextrose. Inpatient treatment consisted primarily of glucose supplementation and supportive care. Questions: In this individual, at the time of presentation, what is the relative ratios of the following hormones: insulin epinephrine glucagon cortisol Based on the data presented above. This individual most likely has a primary deficiency in which of the following pathways. Please describe why you choose a specific pathway and why you DID NOT choose other pathways. a. Glycogenolysis b. Gluconeogenesis c. Lipolysis d. Glycogen synthesis e. Glycolysis f. Ketogenesis g. β-oxidation h. Protein catabolism Based on your choice above, would the use of carnitine supplementation be of any benefit to your patient? (Review the role of carnitine!)

Answer 1

As blood glucose levels were extremely low, so, there would be increased levels of glucagon, epinephrine and cortisol while decreased levels of insulin.

Primary deficiency is in protein catabolism pathway

Reason: The patient is unable to catabolize certain amino acids such as lysine, tryptophan, isoleucine etc which causes build up of glutaric acid, ethyl malonic acid and dicarboxylic acids in urine. Condition is termed as Acidemia

a. Glycogenolysis : Not affected as glycogen administeration increased glucose level

b. Gluconeogenesis : Not affected as no ketones or amino acids were found in urine

c. Lipolysis : Not affected as no lipids were found accumulated

d. Glycogen synthesis : Not affected as glycogen was there which let her survive for 24 hours

e. Glycolysis : Not affected as glucose was catabolized properly

f. Ketogenesis : Not affected as no ketones were found

g. β-​ oxidation : Not affected as no fatty acids were found in urine and level in blood was only slightly high

Role of carnitine : Administeration of carnitine will tend to neutralize the acids present in urine and hence aids in their detoxification.