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Open Access 01-12-2013 | Research

SURF1 deficiency: a multi-centre natural history study

Authors: Yehani Wedatilake, Ruth M Brown, Robert McFarland, Joy Yaplito-Lee, Andrew A M Morris, Mike Champion, Phillip E Jardine, Antonia Clarke, David R Thorburn, Robert W Taylor, John M Land, Katharine Forrest, Angus Dobbie, Louise Simmons, Erlend T Aasheim, David Ketteridge, Donncha Hanrahan, Anupam Chakrapani, Garry K Brown, Shamima Rahman

Published in: Orphanet Journal of Rare Diseases | Issue 1/2013

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.

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 < 0.001) compared to LRPPRC deficiency (median 1.8 years) and nuclear-encoded complex I-deficient LS (median 1.6 years). Survival >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>A (p.Arg192Gln), c.751+5G>A and c.752-2A>G) were identified.

Conclusions

SURF1-deficient patients have a homogeneous clinical and biochemical phenotype. Early recognition is essential to expedite diagnosis and enable prenatal diagnosis.

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Title: SURF1 deficiency: a multi-centre natural history study
Authors: Yehani Wedatilake
Ruth M Brown
Robert McFarland
Joy Yaplito-Lee
Andrew A M Morris
Mike Champion
Phillip E Jardine
Antonia Clarke
David R Thorburn
Robert W Taylor
John M Land
Katharine Forrest
Angus Dobbie
Louise Simmons
Erlend T Aasheim
David Ketteridge
Donncha Hanrahan
Anupam Chakrapani
Garry K Brown
Shamima Rahman
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2013
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/1750-1172-8-96

At a glance: The STEP trials

Springer Medicine

SURF1 deficiency: a multi-centre natural history study

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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