A 14-month-old girl is brought to the emergency department due to progressive lethargy, vo… — USMLE Step 2 CK

A $14$ -month-old girl is brought to the emergency department due to progressive lethargy, vomiting, and rapid breathing over the past $24$ hours. Two days ago, she developed a mild viral upper respiratory tract infection. Her parents report that she had been developing normally until $8$ months of age, but she subsequently lost the ability to sit unsupported and no longer babbles. Vital signs reveal a temperature of $37.6^\circ\text{C}$ ( $99.7^\circ\text{F}$ ), heart rate of $165/\text{min}$ , respiratory rate of $55/\text{min}$ , and blood pressure of $80/40\text{ mm Hg}$ . Physical examination is notable for marked hypotonia, diminished deep tendon reflexes, and deep, rapid, unlabored respirations without wheezing or crackles.

Laboratory studies show:
* Sodium: $138\text{ mEq/L}$
* Potassium: $4.8\text{ mEq/L}$
* Chloride: $102\text{ mEq/L}$
* Bicarbonate: $10\text{ mEq/L}$
* Blood glucose: $45\text{ mg/dL}$
* Blood urea nitrogen: $18\text{ mg/dL}$
* Creatinine: $0.4\text{ mg/dL}$

Arterial blood gas (room air):
* pH: $7.15$
* **PaCO $_2$ **: $28\text{ mm Hg}$
* **PaO $_2$ **: $98\text{ mm Hg}$

Urine organic acid analysis demonstrates massively elevated levels of methylmalonic acid.

Which of the following statements regarding this patient's condition and clinical presentation is most accurate?

The underlying etiology of this patient's metabolic crisis involves a deficient enzyme that utilizes cobalamin as an essential cofactor.Cevap
B
The arterial blood gas results demonstrate that the patient has successfully mounted the appropriate respiratory compensation for her acid-base disturbance.
C
The patient's current motor abilities, including her inability to sit without support, represent a normal physiologic variant of motor development for a 14-month-old child.
D
The patient's marked tachypnea in the setting of a viral prodrome suggests an acute asthma exacerbation requiring immediate administration of nebulized bronchodilators.
E
The most critical initial intervention is the empiric administration of broad-spectrum intravenous antibiotics to manage severe sepsis and prevent further decompensation.

Cevap

The underlying etiology of this patient's metabolic crisis involves a deficient enzyme that utilizes cobalamin as an essential cofactor.

The patient's clinical presentation of developmental regression, severe hypotonia, high anion gap metabolic acidosis (

26\text{ mEq/L}

), hypoglycemia, and elevated urine methylmalonic acid is diagnostic of methylmalonic acidemia. This organic acidemia is primarily caused by an autosomal recessive deficiency of the enzyme methylmalonyl-CoA mutase, which catalyzes the isomerization of L-methylmalonyl-CoA to succinyl-CoA for entry into the TCA cycle. This crucial enzymatic reaction requires vitamin B12 (cobalamin) in the form of adenosylcobalamin as an essential cofactor. In times of catabolic stress (such as a mild viral infection or fasting), the breakdown of odd-chain fatty acids and specific amino acids (valine, isoleucine, methionine, threonine) overwhelms the impaired pathway. This leads to a toxic accumulation of methylmalonic acid, resulting in the observed metabolic crisis, including hypoglycemia (due to secondary inhibition of gluconeogenesis) and profound high anion gap metabolic acidosis.

Adım Adım Çözüm

Calculate the anion gap to characterize the metabolic acidosis.

Anion gap =

138 - (102 + 10) = 26\text{ mEq/L}

. The patient has a high anion gap metabolic acidosis.

Evaluating the specific type of acid-base status is the critical first step in diagnosing the etiology of tachypnea and lethargy in an acutely ill infant.

Determine if respiratory compensation is adequate using Winter's formula.

Expected PaCO

_2 = (1.5 \times 10) + 8 = 23 \pm 2\text{ mm Hg}

. The measured PaCO

_2

28\text{ mm Hg}

, which is higher than expected. This indicates a superimposed primary respiratory acidosis.

Identifying mixed acid-base disorders is critical for recognizing impending respiratory failure in neuromuscularly compromised or profoundly hypotonic patients.

Synthesize the clinical presentation, laboratory findings, and motor milestone history.

The combination of a high anion gap metabolic acidosis, hypoglycemia, marked developmental regression (loss of sitting ability), hypotonia, and massively elevated methylmalonic acid confirms a diagnosis of methylmalonic acidemia.

The clinical triad of developmental regression, a severe metabolic crisis triggered by a minor illness, and specific urinary organic acids definitively points to this inborn error of metabolism.

Identify the underlying biochemical defect and its associated cofactor.

Methylmalonic acidemia is most commonly caused by a deficiency in methylmalonyl-CoA mutase. This enzyme specifically requires vitamin B12 (cobalamin) as a cofactor to function.

Understanding the biochemical pathway is necessary to determine potential targeted therapies, such as cobalamin supplementation for responsive forms of the disease.

Anahtar Kavram

Methylmalonic acidemia pathophysiology and diagnosis

Soru

Cevap

Adım Adım Çözüm

Anahtar Kavram

Sık Yapılan Hatalar

Konular

Bu konudan daha fazla soru