Early-onset cerebellar ataxia, myoclonus and hypogonadism in a case of mitochondrial complex III deficiency treated with vitamins K3 and C.
A 16-year-old girl presented with early-onset cerebellar ataxia, myoclonus, elevated lactic acidosis and hypogonadotropic hypogonadism. Muscle biopsy specimens revealed fibres with a "ragged" appearance with increased mitochondria and lipid droplets. Biochemical investigation revealed a deficiency of complex bc1 (complex III) of the mitochondrial respiratory chain. Genetic analysis did not show either deletions or known mutations of mitochondrial DNA (mtDNA). Phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective energy metabolism in brain and gastrocnemius muscle. A decreased phosphocreatine (PCr) content was found in the occipital lobes accompanied by normal inorganic phosphate (Pi) and cytosolic pH. These findings represented evidence of a high cytosolic adenosine diphosphate concentration and a relatively high rate of metabolism accompanied by a low phosphorylation potential. Muscle 31P-MRS showed a high Pi content at rest, abnormal exercise transfer pattern and a low rate of PCr post-exercise recovery. These findings suggested a deficit of mitochondrial function. Therapy with vitamins K3 and C normalized brain 31P-MRS indices, whereas it did not affect muscle bioenergetic metabolism. In this patient, the endocrinological disorder is putatively due to a mitochondrial cytopathy. Although an unknown mtDNA mutation cannot be ruled out, the genetic defect may lie in the nuclear genome.
Toscano
A
A
Istituto di Scienze Neurologiche e Neurochirurgiche, Università di Messina, Italy.
Fazio
M C
MC
Vita
G
G
Cannavó
S
S
Bresolin
N
N
Bet
L
L
Prelle
A
A
Barbiroli
B
B
Iotti
S
S
Zaniol
P
P
D000293:Adolescent; D017668:Age of Onset; D001205:Ascorbic Acid / Q000627:therapeutic use*; D003241:Consanguinity; D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III / Q000172:deficiency*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D002527:Myoclonic Cerebellar Dyssynergia / Q000209:etiology*; D014812:Vitamin K / Q000627:therapeutic use*
D004272:DNA, Mitochondrial; D014812:Vitamin K; D014450:Electron Transport Complex III; D001205:Ascorbic Acid