A 4-month-old female infant is evaluated in the pediatric emergency department for a 2-day… — USMLE Step 2 CK

A $4$ -month-old female infant is evaluated in the pediatric emergency department for a $2$ -day history of worsening respiratory distress and poor feeding. Her parents state she has always been a "floppy" baby. On physical examination, the infant is tachypneic with intercostal retractions. She exhibits profound generalized hypotonia, a weak cry, and an enlarged, protruding tongue. The parents mention she is unable to sit without support or transfer objects from hand to hand. Auscultation reveals a gallop rhythm and diffuse expiratory wheezing. Chest radiograph demonstrates massive cardiomegaly. Laboratory findings include a serum TSH of $2.1\ \mu\text{U/mL}$ (normal: $0.5-5.0$ ) and Free T4 of $1.4\ \text{ng/dL}$ (normal: $0.9-1.7$ ). An arterial blood gas on room air shows:

pH: $7.25$
$\text{pCO}_2$ : $60\ \text{mmHg}$
$\text{HCO}_3^-$ : $26\ \text{mEq/L}$

Which of the following statements regarding this patient's clinical picture is most accurate?

The patient's condition is caused by a deficiency of acid alpha-glucosidase, leading to lysosomal glycogen accumulation.Answer
B
The arterial blood gas reveals an uncompensated primary metabolic acidosis that requires immediate sodium bicarbonate infusion.
C
The diffuse expiratory wheezing confirms a diagnosis of pediatric asthma, necessitating inhaled albuterol therapy.
D
The combination of macroglossia and hypotonia is explained by primary hypothyroidism, as evidenced by the thyroid function tests.
E
The inability to sit without support at 4 months of age is a definitive sign of delayed motor milestones.

Answer

The condition is caused by a deficiency of acid alpha-glucosidase, leading to lysosomal glycogen accumulation.

The correct answer accurately identifies the underlying pathophysiology of Pompe disease (Glycogen Storage Disease Type II). This autosomal recessive disorder is caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). The resulting accumulation of glycogen within lysosomes severely damages muscle tissue, characteristically presenting in early infancy with profound hypotonia ('floppy baby'), macroglossia, and massive cardiomegaly that frequently progresses to heart failure and respiratory distress.

Step-by-Step Solution

Analyze the clinical presentation and physical examination findings.

The infant exhibits profound hypotonia, macroglossia, and massive cardiomegaly.

These specific signs form the classic clinical triad of Pompe disease (Glycogen Storage Disease Type II).

Evaluate the arterial blood gas values.

The ABG demonstrates a pH of 7.25, pCO2 of 60 mmHg, and normal HCO3-.

This confirms acute uncompensated respiratory acidosis due to cardiopulmonary failure, ruling out a primary metabolic acidosis.

Review the laboratory data and developmental history.

Thyroid function tests are normal. The inability to sit unsupported is appropriate for a 4-month-old.

This systematically rules out congenital hypothyroidism and prevents the misclassification of normal physiological development as an isolated neurological delay.

Identify the biochemical mechanism of the suspected disease.

Pompe disease is caused by an autosomal recessive defect in lysosomal acid alpha-glucosidase.

This enzyme deficiency leads to toxic accumulation of glycogen in lysosomes, predominantly destroying cardiac and skeletal muscle tissue.

Key Concept

Pompe disease (Glycogen Storage Disease Type II) presents in early infancy with profound hypotonia, macroglossia, and massive cardiomegaly due to acid alpha-glucosidase deficiency.

Estimated Time:1m 30s

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