A 14-month-old girl is brought to the emergency department by her parents due to a general… — USMLE Step 2 CK

A $14$ -month-old girl is brought to the emergency department by her parents due to a generalized tonic-clonic seizure and subsequent unresponsiveness. The parents report that she has had a mild upper respiratory tract infection for the past $48$ hours and has refused to eat or drink anything since yesterday evening. Prior to this illness, she had no medical issues and her growth and development were appropriate for her age. On physical examination, the patient is obtunded. Her temperature is $37.6^\circ\text{C}$ ( $99.7^\circ\text{F}$ ), heart rate is $150/\text{min}$ , respiratory rate is $26/\text{min}$ , and blood pressure is $82/50\text{ mmHg}$ . The liver edge is palpable $4\text{ cm}$ below the right costal margin.

Laboratory results are as follows:

Laboratory Test	Result	Reference Range
Serum sodium	$138\text{ mEq/L}$	$135-145\text{ mEq/L}$
Serum potassium	$4.1\text{ mEq/L}$	$3.5-5.0\text{ mEq/L}$
Serum chloride	$104\text{ mEq/L}$	$98-106\text{ mEq/L}$
Serum bicarbonate	$23\text{ mEq/L}$	$22-28\text{ mEq/L}$
Serum glucose	$34\text{ mg/dL}$	$70-100\text{ mg/dL}$
AST	$450\text{ U/L}$	$10-40\text{ U/L}$
ALT	$520\text{ U/L}$	$7-56\text{ U/L}$
Ammonia	$45\ \mu\text{mol/L}$	$15-50\ \mu\text{mol/L}$

Urinalysis is negative for ketones.

Which of the following is the most likely underlying biochemical defect in this patient?

Impaired mitochondrial fatty acid beta-oxidationCevap
B
Defective hepatic glycogenolysis
C
Deficiency of methylmalonyl-CoA mutase
D
Decreased activity of lysosomal alpha-1,4-glucosidase
E
Deficiency of galactose-1-phosphate uridyltransferase

Cevap

The most likely underlying biochemical defect is impaired mitochondrial fatty acid beta-oxidation, specifically medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

The correct answer is impaired mitochondrial fatty acid beta-oxidation. This patient presents with severe hypoglycemia, hepatomegaly, elevated liver transaminases, and absent urine ketones following a short period of fasting (due to a viral illness). This classic presentation—hypoketotic hypoglycemia—is highly suggestive of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. MCAD is the most common enzyme defect in the beta-oxidation of fatty acids. During periods of prolonged fasting or physiological stress, glycogen stores are rapidly depleted, and the body normally relies on fatty acid oxidation to generate acetyl-CoA. Acetyl-CoA is necessary to drive gluconeogenesis and to synthesize ketone bodies (an alternative energy source for the brain). When beta-oxidation is impaired, patients rapidly develop severe, life-threatening hypoglycemia without appropriate compensatory ketogenesis, leading to lethargy, seizures, and potentially coma. The accumulation of fatty acid intermediates in the liver also causes hepatomegaly and hepatocellular damage, reflected by the elevated transaminases.

Adım Adım Çözüm

Analyze the patient's acute presentation and laboratory findings.

The patient has profound hypoglycemia (

34\text{ mg/dL}

), hepatomegaly, elevated liver enzymes (AST

450\text{ U/L}

, ALT

520\text{ U/L}

), and negative urine ketones despite a

24

-hour fasting period.

Identifying the combination of severe hypoglycemia and the unexpected absence of compensatory ketones is the critical first step in categorizing the metabolic disorder.

Evaluate the patient's acid-base status from the basic metabolic panel.

The serum bicarbonate is normal (

23\text{ mEq/L}

), indicating the absence of significant metabolic acidosis or lactic acidosis.

Checking the acid-base balance rapidly differentiates between organic acidemias/glycogen storage diseases (which cause severe acidosis) and fatty acid oxidation defects (which typically do not).

Synthesize the findings to determine the precise biochemical defect.

Hypoketotic hypoglycemia without metabolic acidosis in a previously healthy, fasting toddler points directly to an inability to utilize fatty acids for energy.

During fasting, fatty acid beta-oxidation is required to provide acetyl-CoA for ketone body synthesis and to drive gluconeogenesis. A defect in this pathway perfectly explains the clinical picture.

Anahtar Kavram

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, a defect in fatty acid beta-oxidation, classically presents in infancy or early childhood with hypoketotic hypoglycemia, lethargy, and hepatomegaly triggered by prolonged fasting or intercurrent illness.

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