Physiology · Year 1 · from Physiology
Case 1: Duchenne Muscular Dystrophy - Structural Protein Deficiency
Clinical Image
Source: Wikimedia Commons - Duchenne muscular dystrophy - Public Domain
Patient Presentation
A 5-year-old boy is brought by his parents to the pediatric clinic because they are concerned about his motor development. He has difficulty keeping up with peers, falls frequently, and has trouble climbing stairs. His parents note that he uses his hands to "walk up" his legs when rising from the floor (Gowers sign). They also noticed that his calves appear unusually large compared to his thin thighs. Family history reveals that his maternal uncle died from a "muscle disease" at age 22.
Demographics
- Age: 5 years
- Sex: Male
- Family history: Maternal uncle died of muscle disease (X-linked inheritance pattern)
Chief Complaint
Progressive proximal weakness, frequent falls, difficulty climbing stairs, and calf enlargement
Physical Examination
- General: Alert, cooperative boy with waddling gait
- Motor:
- Proximal weakness: 3+/5 hip flexors, hip extensors; 4/5 shoulder girdle
- Distal strength relatively preserved: 4+/5 distally
- Positive Gowers sign: Uses hands to climb up legs when rising from floor
- Pseudohypertrophy: Firm, enlarged calves bilaterally
- Gait: Wide-based, lordotic, waddling (Trendelenburg)
- Reflexes: Diminished at knees, present at ankles
- Spine: Lumbar lordosis to compensate for pelvic girdle weakness
- Cardiac: Regular rhythm, no murmur
Workup
- Creatine kinase (CK): 18,500 U/L (markedly elevated; normal <200)
- Genetic testing: Deletion of exons 45-50 in DMD gene on X chromosome
- Muscle biopsy: Absent dystrophin on immunohistochemistry, fiber size variation, increased connective tissue
- ECG: Tall R waves in V1, deep Q waves in lateral leads (early cardiomyopathy)
- Echocardiogram: Normal LV function currently (baseline for monitoring)
- Pulmonary function tests: FVC 92% predicted (baseline for monitoring)
Diagnosis
Duchenne Muscular Dystrophy (DMD)
Treatment
- Glucocorticoids (prednisone or deflazacort) - prolongs ambulation by 2-3 years and preserves pulmonary and cardiac function
- Physical therapy: Stretching to prevent contractures, moderate exercise
- Cardiac monitoring: Annual echocardiogram, ACE inhibitor when EF begins to decline
- Pulmonary monitoring: Annual PFTs, non-invasive ventilation when needed
- Orthopedic management: AFOs for ankle contractures, scoliosis monitoring/surgery
- Nutritional support: Monitor for obesity (steroids) and malnutrition (later stages)
- Genetic counseling for family members
- Consider emerging therapies: Exon-skipping antisense oligonucleotides (eteplirsen for exon 51), gene therapy trials
Physiological Principles Demonstrated
- Dystrophin function: Dystrophin is a cytoskeletal protein that connects intracellular actin to the dystrophin-associated glycoprotein complex (DAGC) in the sarcolemma, which anchors to the extracellular matrix. This creates a mechanical link that transmits force and stabilizes the membrane during contraction.
- Membrane damage without dystrophin: Without dystrophin, the sarcolemma is vulnerable to contraction-induced damage. Membrane tears allow calcium influx, triggering necrosis and eventual replacement with fibrotic and fatty tissue.
- Pseudohypertrophy: Calf enlargement results from replacement of muscle fibers with fat and connective tissue, not true muscle hypertrophy. The tissue is firm but weak.
- X-linked inheritance: The DMD gene is on the X chromosome. Males (XY) with one mutant allele are affected; females (XX) are usually asymptomatic carriers but may have elevated CK or mild symptoms due to skewed X-inactivation.
- CK elevation: Muscle damage releases creatine kinase into the bloodstream. Markedly elevated CK (>10,000) suggests ongoing muscle breakdown, characteristic of dystrophies.
- Cardiac muscle involvement: Dystrophin is also expressed in cardiac muscle. Progressive cardiomyopathy is a major cause of death in DMD, requiring regular monitoring and early cardioprotective therapy.