{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:02:16Z","timestamp":1791885736120,"version":"4.3.4"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      SURF1 deficiency, a monogenic mitochondrial disorder, is the most frequent cause of cytochrome\n                      <jats:italic>c<\/jats:italic>\n                      oxidase (COX) deficient Leigh syndrome (LS). We report the first natural history study of SURF1 deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:bold>-<\/jats:bold>\n                      Meier survival analysis and logrank test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The majority of patients (32\/44, 73%) presented in infancy (median 9.5\u00a0months). Frequent symptoms were poor weight gain (95%, median age 10\u00a0months), hypotonia (93%, median age 14\u00a0months), poor feeding\/vomiting (89%, median age 10\u00a0months), developmental delay (88%, median age 14\u00a0months), developmental regression (71%, median age 19\u00a0months), movement disorder (52%, median age 24\u00a0months), oculomotor involvement (52%, median age 29\u00a0months) and central respiratory failure (78%, median age 31\u00a0months). Hypertrichosis (41%), optic atrophy (23%), encephalopathy (20%), seizures (14%) and cardiomyopathy (2%) were observed less frequently.<\/jats:p>\n                    <jats:p>Lactate was elevated in CSF (mean 4.3 mmol\/L) in all patients (30\/30) and in blood (mean 4.4 mmol\/L) in 31\/38 (81%). Fibroblast COX activity was universally decreased (25\/25). Normal COX histochemistry was noted in 30% of biopsies, whereas muscle COX activity was reduced in 96% (25\/26). Neuroimaging demonstrated lesions characteristic of LS in 28\/33 (85%) and atypical findings in 3\/33 (9%). Peripheral neuropathy was present in 13\/16 (81%) (demyelinating 7\/16, axonal 2\/16). Kaplan-Meier analysis demonstrated that SURF1-deficient patients experience longer survival (median 5.4 years, p &lt; 0.001) compared to LRPPRC deficiency (median 1.8 years) and nuclear-encoded complex I-deficient LS (median 1.6 years). Survival &gt;10 years was observed in 7 patients, 6 of these patients did not experience neurological regression. The most frequent mutation was c.312_320del10insAT. Five novel mutations (c.468_469delTC, c.799_800delCT, c.575G&gt;A (p.Arg192Gln), c.751+5G&gt;A and c.752-2A&gt;G) were identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SURF1-deficient patients have a homogeneous clinical and biochemical phenotype. Early recognition is essential to expedite diagnosis and enable prenatal diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1750-1172-8-96","type":"journal-article","created":{"date-parts":[[2013,7,5]],"date-time":"2013-07-05T06:14:50Z","timestamp":1373004890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["SURF1 deficiency: a multi-centre natural history study"],"prefix":"10.1186","volume":"8","author":[{"given":"Yehani","family":"Wedatilake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth M","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"McFarland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Yaplito-Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A M","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Champion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip E","family":"Jardine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Thorburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Land","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine","family":"Forrest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus","family":"Dobbie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlend T","family":"Aasheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ketteridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donncha","family":"Hanrahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Chakrapani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry K","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamima","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,7,5]]},"reference":[{"key":"594_CR1","first-page":"928","volume":"2012","author":"A Hannappel","year":"1817","unstructured":"Hannappel A, Bundschuh FA, Ludwig B: Role of Surf1 in heme recruitment for bacterial COX biogenesis. 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