title: Early-onset cerebellar ataxia, myoclonus and hypogonadism in a case of mitochondrial complex III deficiency treated with vitamins K3 and C.
abstract: 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.
authors.affiliation: Istituto di Scienze Neurologiche e Neurochirurgiche, Università di Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: M C
authors.initials: MC
authors.lastname: Fazio
authors.forename: G
authors.initials: G
authors.lastname: Vita
authors.forename: S
authors.initials: S
authors.lastname: Cannavó
authors.forename: N
authors.initials: N
authors.lastname: Bresolin
authors.forename: L
authors.initials: L
authors.lastname: Bet
authors.forename: A
authors.initials: A
authors.lastname: Prelle
authors.forename: B
authors.initials: B
authors.lastname: Barbiroli
authors.forename: S
authors.initials: S
authors.lastname: Iotti
authors.forename: P
authors.initials: P
authors.lastname: Zaniol
mesh_terms: 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*
chemical_list: D004272:DNA, Mitochondrial; D014812:Vitamin K; D014450:Electron Transport Complex III; D001205:Ascorbic Acid