title: Impairment of brain and muscle energy metabolism detected by magnetic resonance spectroscopy in hereditary spastic paraparesis type 28 patients with DDHD1 mutations.
abstract: Mutations in DDHD1 gene have been associated with the SPG28 subtype of Hereditary Spastic Paraparesis (HSP). Clinical phenotype includes axonal neuropathy, distal sensory loss, and cerebellar eye movement disturbances. We screened 96 index subjects from recessive HSP families for mutation and identified one family with two sibs carrying mutations in DDHD1 gene. Clinical, neuropsychological, and neuroimaging studies were performed, including MR spectroscopy of brain and muscle of the two mutated patients. Two novel heterozygous mutations in DDHD1 were found in the affected members of one family, with clinical features overlapping the SPG28 subtype. Of note, MR spectroscopy of brain and muscle in these patients indicated a mild deficit of brain energy metabolism in the oldest and most severely affected patient, while an impairment of energy metabolism was found in the skeletal muscle of both patients. Unlike the DDHD2 mutated patients, no evidence of lipid accumulation in the brain was found. Our data along with those previously reported suggest a dysfunction in the OXPHOS system possibly due to mitochondrial lipid content modification, which could be a central mechanism in the pathogenesis of SPG28.
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche di Bologna, Pad G1, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy, rocco.liguori@unibo.it.
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Giannoccaro
authors.forename: Alessia
authors.initials: A
authors.lastname: Arnoldi
authors.forename: Andrea
authors.initials: A
authors.lastname: Citterio
authors.forename: Caterina
authors.initials: C
authors.lastname: Tonon
authors.forename: Raffaele
authors.initials: R
authors.lastname: Lodi
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology*; D004734:Energy Metabolism / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009154:Mutation; D010264:Paraplegia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D010740:Phospholipases / Q000235:genetics*; D055815:Young Adult
chemical_list: D010740:Phospholipases