Parents arrive at the emergency department with their 5-month-old male infant after he exp… — USMLE Step 2 CK

Parents arrive at the emergency department with their 5-month-old male infant after he experienced a 2-minute episode of generalized extremity stiffening and rhythmic jerking. The parents report that he has been increasingly lethargic over the past 48 hours. During the history, they express concern that he is not yet able to sit up without support. Physical examination reveals a lethargic infant with generalized hypotonia and sparse scalp hair. A prominently erythematous, scaling rash with skin peeling is noted around his mouth and eyes. Vital signs show a heart rate of 152/min and a respiratory rate of 50/min.

Laboratory evaluation reveals the following:

Laboratory Parameter	Result
Serum sodium	$138$ mEq/L
Serum potassium	$4.1$ mEq/L
Serum chloride	$102$ mEq/L
Serum bicarbonate	$12$ mEq/L
Arterial Blood Gas (room air)
$pH$	$7.26$
$pCO_2$	$28$ mmHg
$pO_2$	$96$ mmHg

Which of the following is the most appropriate specific treatment for this patient's underlying condition?

Initiation of oral biotinAnswer
B
Endotracheal intubation and mechanical ventilation
C
Intravenous acyclovir therapy
D
Intravenous ceftriaxone and vancomycin
E
Referral to early intervention for delayed achievement of independent sitting

Answer

The most appropriate specific treatment is the initiation of oral biotin for suspected biotinidase deficiency.

This patient's presentation of seizures, hypotonia, alopecia, a periorificial scaly rash, and an elevated anion gap metabolic acidosis is highly characteristic of biotinidase deficiency. Biotin is a crucial cofactor for multiple carboxylase enzymes (e.g., pyruvate carboxylase, propionyl-CoA carboxylase). A deficiency in biotinidase prevents the recycling of endogenous biotin and the release of dietary biotin, leading to multiple carboxylase deficiency. This results in the accumulation of lactic acid and organic acids, causing a high anion gap metabolic acidosis. The most appropriate specific treatment is the immediate initiation of lifelong oral biotin supplementation, which rapidly reverses the metabolic and cutaneous abnormalities and improves neurologic outcomes.

Step-by-Step Solution

Calculate the anion gap.

Anion gap =

138 - (102 + 12) = 24

mEq/L.

Determining the anion gap is essential to characterize the etiology of the severe metabolic acidosis (

pH

7.26

HCO_3^-

12

mEq/L). The elevated gap indicates the accumulation of unmeasured organic acids, such as lactic acid.

Calculate expected respiratory compensation using Winter's formula.

Expected

pCO_2 = 1.5 \times 12 + 8 \pm 2 = 26 \pm 2

mmHg. The measured

pCO_2

28

mmHg.

This confirms that the patient's tachypnea is an appropriate compensatory response to the metabolic acidosis, ruling out a concurrent primary respiratory failure.

Synthesize the clinical and laboratory findings.

The combination of high anion gap metabolic acidosis, seizures, hypotonia, alopecia, and an erythematous periorificial skin rash in an infant forms a classic syndromic presentation.

This triad (neurologic, cutaneous, and metabolic derangements) specifically points to biotinidase deficiency, a defect in the recycling of the essential cofactor biotin.

Determine the targeted management strategy.

Initiation of lifelong oral biotin supplementation.

Providing exogenous biotin overcomes the enzyme deficiency, rapidly reversing the metabolic and cutaneous manifestations and halting the progression of neurologic damage.

Key Concept

Biotinidase deficiency is an inborn error of metabolism that presents in infancy with a classic triad of neurologic abnormalities (seizures, hypotonia), cutaneous findings (alopecia, periorificial scaly dermatitis), and a high anion gap metabolic acidosis (lactic acidosis). It is treated with lifelong oral biotin supplementation.

Estimated Time:1m 30s

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