Diagnosis of mitochondrial diseases: clinical and histological study of sixty patients with ragged red fibers.
BACKGROUND
Mitochondrial diseases are caused by mutations in mitochondrial or nuclear genes, or both and most patients do not present with easily recognizable disorders. The characteristic morphologic change in muscle biopsy, ragged-red fibers (RRFs) provides an important clue to the diagnosis.


METHODS
Demographic data, presenting symptoms, neurological features, and investigative findings in 60 patients with ragged-red fibers (RRFs) on muscle biopsy, seen between January 1990 and December 2002, were analyzed. The authors applied the modified respiratory chain (RC) diagnostic criteria retrospectively to determine the number of cases fulfilling the diagnostic criteria of mitochondrial disease.


RESULTS
The most common clinical syndrome associated with RRFs on muscle biopsy was progressive external ophthalmoplegia (PEO) with or without other signs, in 38 (63%) patients. Twenty-six patients (43%) had only external ophthalmoplegia, 5 (8%) patients presented with encephalomyopathy. Specific syndromes were the presenting feature in 8 (13%), Kearns-Sayre syndrome (KSS) in 4 and myoclonus epilepsy with ragged-red fibers (MERRF) in 4. Myopathy was the presenting feature in 5 (8%) and 4 presented with infantile myopathy. Of the 60 patients, 18 (30%) had proximal muscle weakness. Two patients with KSS and one patient with myopathy had complete heart block necessitating pace making. When the modified RC diagnostic criteria were applied, only 26 (43%) patients had one other major criterion in addition to RRFs for the diagnosis of mitochondrial diseases. The remaining 34 (57%) patients with RRFs on muscle biopsy had only some clinical features suggestive of RC disorder but did not fulfill the clinical criteria (of the modified diagnostic criteria) for the diagnosis of mitochondrial diseases.


CONCLUSIONS
In patients with clinical features suggestive of RC disorder, demonstration of RRFs on muscle biopsy helps in confirming the diagnosis of mitochondrial disease in only a subgroup of patients.
Challa
Sundaram
S
Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, India. challa_sundaram@yahoo.com.
Kanikannan
Meena A
MA
Murthy
Jagarlapudi Mk
JM
Bhoompally
Venkateswar R
VR
Surath
Mohandas
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology
D003402:Creatine Kinase