A 9-day-old female infant is admitted to the neonatal intensive care unit for profound let… — USMLE Step 2 CK

A 9-day-old female infant is admitted to the neonatal intensive care unit for profound lethargy, tachypnea, and recurrent vomiting. She was born at full term via uncomplicated delivery and appeared well until two days ago when breastfeeding was supplemented with a cow's milk-based formula. On examination, the infant is unresponsive to tactile stimuli and exhibits generalized hypotonia.

Laboratory studies are as follows:

Test	Result
Arterial Blood Gas
pH	7.18
$pCO_2$	18 mm Hg
$pO_2$	98 mm Hg
Serum Chemistry
Sodium	142 mEq/L
Potassium	5.1 mEq/L
Chloride	99 mEq/L
Bicarbonate	7 mEq/L
Blood urea nitrogen	14 mg/dL
Creatinine	0.3 mg/dL
Glucose	48 mg/dL
Ammonia	720 $\mu$ mol/L (normal: 15-50 $\mu$ mol/L)
Urinalysis
Ketones	+++
Reducing substances	Negative

Restriction of which of the following groups of amino acids is most critical for the long-term management of this patient's underlying condition?

A
Leucine, isoleucine, and valine
Methionine, threonine, and valineCevap
C
Phenylalanine and tyrosine
D
Arginine and citrulline
E
Lysine and tryptophan

Cevap

Methionine, threonine, and valine

The correct answer identifies the amino acids that feed into the propionyl-CoA metabolic pathway. This patient's clinical presentation (neonatal encephalopathy after a protein load) and laboratory findings (severe high anion gap metabolic acidosis, ketonuria, hypoglycemia, and massive hyperammonemia) are the hallmark features of an organic acidemia, most likely propionic acidemia or methylmalonic acidemia. The hyperammonemia in organic acidemias is secondary to the toxic inhibition of the urea cycle enzyme carbamoyl phosphate synthetase I (CPS-I) by accumulating organic acid intermediates. Because the defect lies in the metabolism of propionyl-CoA to succinyl-CoA, treatment involves a low-protein diet strictly restricting the precursors to propionyl-CoA. These precursors include Valine, Odd-chain fatty acids, Methionine, Isoleucine, and Threonine.

Adım Adım Çözüm

Analyze the acid-base status and calculate the anion gap.

The patient has a severe metabolic acidosis (pH 7.18, HCO3 7 mEq/L) with appropriate respiratory compensation (

pCO_2

18 mm Hg). The anion gap is 142 - (99 + 7) = 36 mEq/L, indicating a primary high anion gap metabolic acidosis.

Differentiating between causes of neonatal encephalopathy requires classifying the primary acid-base disturbance.

Interpret the associated laboratory findings in the context of the acidosis.

The patient has marked hyperammonemia (720

\mu

mol/L), ketotic hypoglycemia (glucose 48 mg/dL, positive urine ketones), and encephalopathy following the introduction of standard formula (protein load).

The combination of high anion gap metabolic acidosis, hyperammonemia, and ketonuria points toward a specific category of inborn errors of metabolism.

Differentiate organic acidemias from urea cycle defects (UCDs) and fatty acid oxidation defects (FAODs).

UCDs cause primary respiratory alkalosis without primary acidosis. FAODs cause hypoketotic hypoglycemia. The presence of high anion gap metabolic acidosis with ketonuria and massive secondary hyperammonemia is diagnostic for an organic acidemia.

Accurate categorization allows for identification of the underlying defective metabolic pathway.

Identify the affected metabolic pathway and necessary dietary modifications.

Propionic and methylmalonic acidemias result from defects in the breakdown of propionyl-CoA. The precursors for this pathway are Valine, Odd-chain fatty acids, Methionine, Isoleucine, and Threonine (VOMIT). Therefore, these specific amino acids must be restricted in the diet.

Long-term management of organic acidemias requires limiting the specific precursors that cannot be metabolized.

Anahtar Kavram

Neonatal presentation of organic acidemias (e.g., methylmalonic or propionic acidemia) features high anion gap metabolic acidosis, ketotic hypoglycemia, and secondary hyperammonemia. Management requires restricting precursor amino acids that feed into propionyl-CoA: Valine, Methionine, Isoleucine, and Threonine.

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