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Zorluk: ZorPediatric Genetic and Metabolic Disorders

A 4-month-old boy is brought to the emergency department due to progressive feeding difficulties, a weak cry, and rapid breathing. Over the past month, his parents noticed he becomes exhausted and sweaty during feeds. He smiles socially and coos interactively, but he has not yet been able to roll over or hold his head up. His temperature is 37.1°C (98.8°F), blood pressure is 85/50 mm Hg, pulse is 165/min, and respiratory rate is 65/min. Physical examination reveals a lethargic infant with a protruding tongue and generalized hypotonia. When pulled to a sitting position, he exhibits severe head lag. Deep tendon reflexes are absent. Lung auscultation reveals bilateral basilar crackles and scattered wheezes. The liver edge is palpated 4 cm below the right costal margin. A chest radiograph demonstrates massive cardiomegaly. Electrocardiography shows short PR intervals and large QRS complexes.

Laboratory studies show:
Arterial blood gas:
pH: 7.30
pCO2: 54 mm Hg
Bicarbonate: 26 mEq/L

Serum creatine kinase: 1,850 U/L (normal: 22-198 U/L)

Which of the following is the most likely underlying etiology of this patient's clinical presentation?

  1. Defective lysosomal degradation of glycogenCevap
  2. B
    Deficient hepatic glucose-6-phosphatase
  3. C
    Progressive neuronal loss in the cerebral cortex and anterior horn cells
  4. D
    Viral inflammation of the bronchiolar epithelium
  5. E
    Bacterial infiltration of the myocardial interstitium

Cevap

Defective lysosomal degradation of glycogen
This patient's presentation of profound hypotonia, macroglossia, hypertrophic cardiomyopathy (massive cardiomegaly, short PR intervals), and markedly elevated creatine kinase is the classic presentation of Pompe disease (glycogen storage disease type II). Pompe disease is an autosomal recessive disorder caused by a deficiency of lysosomal acid alpha-glucosidase (also known as acid maltase). This enzyme is responsible for the degradation of glycogen into glucose within lysosomes. Its deficiency leads to toxic accumulation of glycogen primarily within cardiac and skeletal muscle tissue. The resulting muscle weakness accounts for the profound hypotonia, failure to attain motor milestones, and respiratory hypoventilation leading to the acute respiratory acidosis seen on this patient's blood gas.

Adım Adım Çözüm

1
Analyze the patient's neurological and developmental presentation.
The infant has profound generalized hypotonia, absent reflexes, and failure to reach motor milestones (head control, rolling over), while social and language milestones (smiling, cooing) remain perfectly normal for his age.
Differentiating between isolated motor weakness (myopathy or lower motor neuron disease) and global neurodevelopmental delay is critical.
2
Evaluate the cardiac and respiratory findings.
The patient has massive cardiomegaly, heart failure (crackles, hepatomegaly), and specific ECG changes (short PR, large QRS). The respiratory distress is accompanied by a primary respiratory acidosis (pH 7.30, elevated pCO2 54, normal bicarbonate 26).
Identifying hypertrophic cardiomyopathy combined with respiratory hypoventilation narrows the differential diagnosis significantly.
3
Synthesize the multisystem clinical picture with laboratory data.
The combination of a "floppy baby" with macroglossia, severe hypertrophic cardiomyopathy, elevated creatine kinase, and hypoventilation is the classic triad for Pompe disease.
This specific cluster of findings is pathognomonic for a specific inborn error of metabolism.
4
Identify the underlying molecular etiology of the identified syndrome.
Pompe disease is Glycogen Storage Disease type II, caused by a deficiency in lysosomal acid alpha-glucosidase (acid maltase), leading to defective lysosomal degradation of glycogen.
The question directly asks for the etiology corresponding to the clinical diagnosis.

Anahtar Kavram

Pompe disease (Glycogen storage disease type II) is a lysosomal storage disorder causing glycogen accumulation in cardiac and skeletal muscle, presenting in infancy with profound hypotonia, macroglossia, and severe hypertrophic cardiomyopathy.
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Pediatric Genetic and Metabolic Disorders

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