Contributed by Amy Davis, MD
Published on line in September 2006
Following an unremarkable prenatal course, a full-term male was floppy at birth and experienced respiratory difficulty. By one month of age, decreased proximal shoulder tone and head lag were apparent. Despite physical therapy, gross motor skills lagged. By 20 months of age, an EMG showed decreased activation of motor units. The patient walked with flat arches and an awkward gait and had bilateral ptosis. Reflexes were difficult to elicit. At the age of four, he developed dilated cardiomyopathy with an ejection fraction as low as 10%. Heart transplantation was performed.
The 212-gram explanted heart (73 gram expected) demonstrated left ventricular and septal hypertrophy (image 1). The septum measured 1.2cm in thickness, and bulged into the right ventricular cavity, imparting a slit-like appearance.
LIGHT AND ELECTRON MICROSCOPIC FINDINGS:
Light microscopy reveals diffuse myocyte hypertrophy and nuclear pleomorphism without intramyocardial fibrosis. The right ventricle, left ventricle and septum contain myofibers that are distorted by intracytoplasmic, pale, waxy hyaline inclusions that range in size from small to massive (image 2). Conduction fibers are grossly swollen, and appear to be preferentially involved. A trichrome stain highlights the pale pink inclusions against a red background (image 3). Desmin immunohistochemical staining is variable, with dense staining of inclusions in some areas and faint to no staining in others (image 4). Inclusions are PAS negative and not congophilic. Electron microscopy reveals filamentous and fibrillar inclusions (image 5). Streaming disruption of Z-bands is prominent. Inclusions push the myofilaments aside and disrupt the cytoplasm with accumulation of mitochondria against the cell membrane. Many inclusions contain conspicuous Z-band material. In others, endoplasmic reticular structures are noted.