title: SURF1 deficiency: a multi-centre natural history study.
abstract: BACKGROUND
  SURF1 deficiency, a monogenic mitochondrial disorder, is the most frequent cause of cytochrome c oxidase (COX) deficient Leigh syndrome (LS). We report the first natural history study of SURF1 deficiency.
  
  
  METHODS
  We conducted a multi-centre case notes review of 44 SURF1-deficient patients from ten different UK centres and two Australian centres. Survival data for LRPPRC-deficient LS and nuclear-encoded complex I-deficient LS patients were obtained from previous publications. The survival of SURF1-deficient patients was compared with these two groups using Kaplan-Meier survival analysis and logrank test.
  
  
  RESULTS
  The majority of patients (32/44, 73%) presented in infancy (median 9.5 months). Frequent symptoms were poor weight gain (95%, median age 10 months), hypotonia (93%, median age 14 months), poor feeding/vomiting (89%, median age 10 months), developmental delay (88%, median age 14 months), developmental regression (71%, median age 19 months), movement disorder (52%, median age 24 months), oculomotor involvement (52%, median age 29 months) and central respiratory failure (78%, median age 31 months). Hypertrichosis (41%), optic atrophy (23%), encephalopathy (20%), seizures (14%) and cardiomyopathy (2%) were observed less frequently.
  
  
  CONCLUSIONS
  SURF1-deficient patients have a homogeneous clinical and biochemical phenotype. Early recognition is essential to expedite diagnosis and enable prenatal diagnosis.
authors.forename: Yehani
authors.initials: Y
authors.lastname: Wedatilake
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Brown
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Joy
authors.initials: J
authors.lastname: Yaplito-Lee
authors.forename: Andrew A M
authors.initials: AA
authors.lastname: Morris
authors.forename: Mike
authors.initials: M
authors.lastname: Champion
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Jardine
authors.forename: Antonia
authors.initials: A
authors.lastname: Clarke
authors.forename: David R
authors.initials: DR
authors.lastname: Thorburn
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: John M
authors.initials: JM
authors.lastname: Land
authors.forename: Katharine
authors.initials: K
authors.lastname: Forrest
authors.forename: Angus
authors.initials: A
authors.lastname: Dobbie
authors.forename: Louise
authors.initials: L
authors.lastname: Simmons
authors.forename: Erlend T
authors.initials: ET
authors.lastname: Aasheim
authors.forename: David
authors.initials: D
authors.lastname: Ketteridge
authors.forename: Donncha
authors.initials: D
authors.lastname: Hanrahan
authors.forename: Anupam
authors.initials: A
authors.lastname: Chakrapani
authors.forename: Garry K
authors.initials: GK
authors.lastname: Brown
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007888:Leigh Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency*; D024101:Mitochondrial Proteins / Q000172:deficiency*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C092928:Surf-1 protein; D003576:Electron Transport Complex IV