We report a 9 year-old boy with
MELAS. High dosed oral
thiamine administration and high fat diet induced remarkable neurological and biochemical improvement. His mother had episodic
headaches and
hemiplegia, probably
MELAS. He complained
muscle weakness and repeated episodes of
vomiting started from 2 years of age. High levels of serum
lactate and
pyruvate were recognized, but with no
metabolic acidosis. He developed generalized
muscle weakness, growth retardation, generalized convulsions and
stroke-like episodes at 5 years old. Optic nerve
atrophy and
mental retardation gradually appeared. A muscle biopsy at 5 years old revealed numerous ragged-red fibers with excess accumulation of lipid droplets and
glycogen particles. Scattered fibers had no
cytochrome c oxidase (CCO) activity representing focal CCO deficiency. An electron microscopy showed markedly increased number of giant mitochondria filled with markedly proliferated complicated cristae.
Pyruvate dehydrogenase complex level in the fibroblasts was within normal ranges. Serum
carnitine level was normal. With
oral administration of
thiamine hydrochloride (1000 mg) and high fat diet (60-70%),
muscle weakness improved, and
lactate and
pyruvate levels in the serum reduced to normal ranges, whereas the
mental deterioration,
muscle atrophy,
pes cavus progressed very slowly. He died from cardiac and
renal failures at 9 years old. Autopsied muscles showed a marked decrease in
cytochrome c oxidase activity (biochemically 12.8% of the normal level), and almost all muscle fibers had no
cytochrome c oxidase activity histochemically. The progression of the
MELAS was probably in parallel with the decrease in CCO activity.