SURF1 deficiency: a multi-centre natural history study

Yehani Wedatilake; Ruth M. Brown; Robert McFarland; Joy Yaplito-Lee; Andrew A. M. Morris; Michael 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

doi:10.1186/1750-1172-8-96

SURF1 deficiency: a multi-centre natural history study

Yehani Wedatilake, Ruth M. Brown, Robert McFarland, Joy Yaplito-Lee, Andrew A. M. Morris, Michael 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

112 Citations (Scopus)

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.

Original language	English
Article number	96
Number of pages	13
Journal	Orphanet Journal of Rare Diseases
Volume	8
DOIs	https://doi.org/10.1186/1750-1172-8-96
Publication status	Published - 5 Jul 2013

Keywords

SURF1
Leigh syndrome
Cytochrome c oxidase
Complex IV
Mitochondrial disease
CYTOCHROME-C-OXIDASE
LEIGH-SYNDROME
GENE-MUTATIONS
PERIPHERAL NEUROPATHY
MISSENSE MUTATIONS
CLINICAL-FEATURES
COX DEFICIENCY
DISEASE
BIOGENESIS
MRI

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Wedatilake, Y., Brown, R. M., McFarland, R., Yaplito-Lee, J., Morris, A. A. M., Champion, M., Jardine, P. E., Clarke, A., Thorburn, D. R., Taylor, R. W., Land, J. M., Forrest, K., Dobbie, A., Simmons, L., Aasheim, E. T., Ketteridge, D., Hanrahan, D., Chakrapani, A., Brown, G. K., & Rahman, S. (2013). SURF1 deficiency: a multi-centre natural history study. Orphanet Journal of Rare Diseases, 8, Article 96. https://doi.org/10.1186/1750-1172-8-96

@article{7568dd75a49f4453adb53c27576b922b,

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. 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.",

keywords = "SURF1, Leigh syndrome, Cytochrome c oxidase, Complex IV, Mitochondrial disease, CYTOCHROME-C-OXIDASE, LEIGH-SYNDROME, GENE-MUTATIONS, PERIPHERAL NEUROPATHY, MISSENSE MUTATIONS, CLINICAL-FEATURES, COX DEFICIENCY, DISEASE, BIOGENESIS, MRI",

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

year = "2013",

month = jul,

day = "5",

doi = "10.1186/1750-1172-8-96",

language = "English",

volume = "8",

journal = "Orphanet Journal of Rare Diseases",

issn = "1750-1172",

publisher = "BioMed Central",

}

Wedatilake, Y, Brown, RM, McFarland, R, Yaplito-Lee, J, Morris, AAM, Champion, M, Jardine, PE, Clarke, A, Thorburn, DR, Taylor, RW, Land, JM, Forrest, K, Dobbie, A, Simmons, L, Aasheim, ET, Ketteridge, D, Hanrahan, D, Chakrapani, A, Brown, GK & Rahman, S 2013, 'SURF1 deficiency: a multi-centre natural history study', Orphanet Journal of Rare Diseases, vol. 8, 96. https://doi.org/10.1186/1750-1172-8-96

TY - JOUR

T1 - SURF1 deficiency

T2 - a multi-centre natural history study

AU - Wedatilake, Yehani

AU - Brown, Ruth M.

AU - McFarland, Robert

AU - Yaplito-Lee, Joy

AU - Morris, Andrew A. M.

AU - Champion, Michael

AU - Jardine, Phillip E.

AU - Clarke, Antonia

AU - Thorburn, David R.

AU - Taylor, Robert W.

AU - Land, John M.

AU - Forrest, Katharine

AU - Dobbie, Angus

AU - Simmons, Louise

AU - Aasheim, Erlend T.

AU - Ketteridge, David

AU - Hanrahan, Donncha

AU - Chakrapani, Anupam

AU - Brown, Garry K.

AU - Rahman, Shamima

PY - 2013/7/5

Y1 - 2013/7/5

N2 - 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.

AB - 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.

KW - SURF1

KW - Leigh syndrome

KW - Cytochrome c oxidase

KW - Complex IV

KW - Mitochondrial disease

KW - CYTOCHROME-C-OXIDASE

KW - LEIGH-SYNDROME

KW - GENE-MUTATIONS

KW - PERIPHERAL NEUROPATHY

KW - MISSENSE MUTATIONS

KW - CLINICAL-FEATURES

KW - COX DEFICIENCY

KW - DISEASE

KW - BIOGENESIS

KW - MRI

U2 - 10.1186/1750-1172-8-96

DO - 10.1186/1750-1172-8-96

M3 - Article

SN - 1750-1172

VL - 8

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

M1 - 96

ER -

SURF1 deficiency: a multi-centre natural history study

Abstract

Keywords

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