A 4-month-old boy is brought to the emergency department after an episode of generalized tonic-clonic seizure 30 minutes ago. The patient was born at 40 weeks gestation by spontaneous vaginal delivery. He was at the 50th percentile for height and weight, and had a normal physical examination. Since birth, the patient has had 3 episodes of upper respiratory infection and otitis media. His parents and older sister have no medical problems. On examination, the patient is lethargic. He weighs 4.2 kg (9.3 lb,

Question

A 4-month-old boy is brought to the emergency department after an episode of generalized tonic-clonic seizure 30 minutes ago.  The patient was born at 40 weeks gestation by spontaneous vaginal delivery.  He was at the 50th percentile for height and weight, and had a normal physical examination.  Since birth, the patient has had 3 episodes of upper respiratory infection and otitis media.  His parents and older sister have no medical problems.  On examination, the patient is lethargic.  He weighs 4.2 kg (9.3 lb, <5th percentile).  The anterior fontanelle is flat.  Pupils are reactive with normal fundi.  His tympanic membranes and pharynx are normal.  He has round cheeks and a doll-like face.  Heart sounds are normal without murmurs.  Lungs are clear.  The abdomen is protuberant and the liver is palpable 4 cm below the right costal margin.  Extremities are thin.  Laboratory results are as follows:  Urine dipstick is positive for ketones.  Serum triglyceride and uric acid levels are increased.  Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

Glucose-6-phosphatase deficiency (type I glycogen storage disease, von Gierke disease) is caused by deficient glucose-6-phosphatase in the liver, kidneys, and intestinal mucosa. This results in impaired conversion of glycogen to glucose, leading to glycogen accumulation in the affected organs. Patients typically present at age 3-4 months with hypoglycemia (often resulting in seizures) and lactic acidosis (due to buildup in the liver). Other laboratory findings include hyperuricemia and hyperlipidemia. Physical examination demonstrates a doll-like face with rounded cheeks, thin extremities, short stature, and a protuberant abdomen due to hepatomegaly. The spleen and heart are not involved. (Choice A) Excessive endogenous insulin production at this age could be a result of persistent hyperinsulinemic hypoglycemia of infancy (PHHI), which would also cause hypoglycemia, poor feeding, and poor tone. However, PHHI is often associated with infants of mothers who are diabetic (whereas this patient's mother has no medical problems) and usually presents in the first few days of life with macrosomia (rather than failure to thrive). (Choice B) Glucocerebrosidase enzyme deficiency results in Gaucher disease. Glucocerebroside accumulates in macrophages of the liver, spleen, and bone marrow, causing bone pain and cytopenias. Hepatosplenomegaly is present, but hypoglycemia and lactic acidosis are not typical. (Choice D) The inability to break down fatty acid chains is a feature of fatty acid cycle disorders such as medium-chain acyl-CoA dehydrogenase deficiency (MCAD). MCAD results in episodes of hypoketotic hypoglycemia during fasting states (eg, illness). Elevated lactic acid, elevated uric acid, and characteristic facial features are not typically seen. (Choice E) Inadequate total body glycogen stores may occur in newborns as a result of prematurity or intrauterine growth restriction. Hypoglycemia is very common in these newborns; however, it typically occurs within the first 24 hours of life, would not persist at age 4 months, and would not be associated with specific facial features. Educational objective: Glucose-6-phosphatase deficiency (type I glycogen storage disease, von Gierke disease) presents at age 3-4 months with hypoglycemia (often with seizures), lactic acidosis, hyperuricemia, and hyperlipidemia. Patients typically have a doll-like face, thin extremities, short stature, and a protuberant abdomen (due to hepatomegaly).

A 4-Month-Old Boy Is Brought to the Emergency Department After