Duchenne Muscular Dystrophy: Journey from Histochemistry to Molecular Diagnosis
- PDF / 279,853 Bytes
- 3 Pages / 612 x 792 pts (letter) Page_size
- 25 Downloads / 201 Views
*[email protected]
The August, 1970 issue of Indian Pediatrics reported an article describing the histopathological and enzyme histochemical features in the muscle biopsy of children with Duchenne muscular dystrophy (DMD) [1]. This article provides an opportunity to introspect on the evolution of diagnosis of children with Duchenne muscular dystrophy. In the present era of molecular genetics, the article provides an insight into the importance of muscle biopsy, which has gradually lost its way in this tale of last 50 years in diagnosis of children with DMD.
in ATPase activity in the muscle fiber and increase in LDH activity in connective tissue to increased fat deposition. Historical Background In late 1860s, Duchenne performed muscle biopsy on a patient with a myopathy. Till 1970s, pathologists largely relied on histopathological features based on routine hematoxylin and eosin staining. Enzyme histochemistry was introduced in the early 1970s. The present article is one of the first few articles that describe the enzyme histochemical features in children with Duchenne muscular dystrophy. Electron microscopy had limited application for muscular dystrophies, but played a major role in the pathological diagnosis of congenital myopathies in the early 1980s [2]. Immunohistochemistry was introduced in 1980s that described absence of dystrophin protein in children with DMD. Western blot also provided qualitative information on expression of proteins in muscular dystrophy [3]. In late 1980s, with the advent of molecular diagnostics, polymerase chain reaction (PCR) was available worldwide and gradually replaced muscle biopsy as the first line investigation for diagnosis of DMD. This technique detects large deletions in 60-65% of patients with DMD. Subsequently, by the year 2003, multiplex ligation probe analysis (MLPA) was introduced for detecting mutations in DMD gene. MLPA is a quantitative method to detect deletion and duplication in all the 79 exons of dystrophin gene, and is also useful in carrier testing.
THE PAST Naryananan, et al. [1] reported a descriptive study on clinical, histopathological and enzyme histochemical features of 23 children with Duchenne muscular dystrophy. Among the 23 patients, 5 children had an onset before 3 years of age while the remaining 18 children had onset between 4 to 10 years of age. Two girls were included in those 23 children with rest being boys. Histopathological features described by authors include marked variation in muscle fibre size with hyaline degeneration of muscle, alteration in sarcoplasmic nuclei with central nuclei and clumps of atrophic nuclei, and increased endomysial connective tissue. Enzyme histochemical analysis revealed increased lactate dehydrogenase activity in the dystrophic muscle fibre suggestive of increased anaerobic metabolism along with decrease in aerobic metabolism in terms of decrease in succinic dehydrogenase. Increased ATPase activity observed in the muscle was postulated by authors to decrease ATP content with consequent impairment of
Data Loading...
