TMEM70 deficiency: long-term outcome of 48 patients
- Author
- Martin Magner, Veronika Dvorakova, Marketa Tesarova, Stella Mazurova, Hana Hansikova, Martin Zahorec, Katarina Brennerova, Vladimir Bzduch, Ronen Spiegel, Yoseph Horovitz, Hanna Mandel, Fatma Tuba Eminoğlu, Jhannes Adalbert Mayr, Johannes Koch, Diego Martinelli, Enrico Bertini, Vassiliki Konstantopoulou, Joél Smet (UGent) , Shamima Rahman, Alexander Broomfield, Vesna Stojanović, Carlo Dionisi-Vici, Rudy Van Coster (UGent) , Eva Morava, Wolgang Sperl, Jiri Zeman and Tomas Honzik
- Organization
- Abstract
- OBJECTIVES: TMEM70 deficiency is the most common nuclear-encoded defect affecting the ATP synthase. In this multicentre retrospective study we characterise the natural history of the disease, treatment and outcome in 48 patients with mutations in TMEM70. Eleven centers from eight European countries, Turkey and Israel participated. RESULTS: All 27 Roma and eight non-Roma patients were homozygous for the common mutation c.317-2A > G. Five patients were compound heterozygotes for the common mutation and mutations c.470 T > A, c.628A > C, c.118_119insGT or c.251delC. Six Arab Muslims and two Turkish patients were homozygous for mutations c.238C > T, c.316 + 1G > T, c.336 T > A, c.578_579delCA, c.535C > T, c.359delC. Age of onset was neonatal in 41 patients, infantile in six cases and two years in one child. The most frequent symptoms at onset were poor feeding, hypotonia, lethargy, respiratory and heart failure, accompanied by lactic acidosis, 3-methylglutaconic aciduria and hyperammonaemia. Symptoms further included: developmental delay (98 %), hypotonia (95 %), faltering growth (94 %), short stature (89 %), non-progressive cardiomyopathy (89 %), microcephaly (71 %), facial dysmorphism (66 %), hypospadias (50 % of the males), persistent pulmonary hypertension of the newborn (22 %) and Wolff-Parkinson-White syndrome (13 %). One or more acute metabolic crises occurred in 24 surviving children, frequently followed by developmental regression. Hyperammonaemic episodes responded well to infusion with glucose and lipid emulsion, and ammonia scavengers or haemodiafiltration. Ten-year survival was 63 %, importantly for prognostication, no child died after the age of five years. CONCLUSION: TMEM70 deficiency is a panethnic, multisystemic disease with variable outcome depending mainly on adequate management of hyperammonaemic crises in the neonatal period and early childhood.
- Keywords
- ATP SYNTHASE, MITOCHONDRIAL, BARTH-SYNDROME, 3-METHYLGLUTACONIC ACIDURIA, ACUTE METABOLIC DECOMPENSATION, ACIDURIA TYPE-IV, MUTATION, GENES, CARDIOMYOPATHY, PROTEIN
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-5745843
- MLA
- Magner, Martin, et al. “TMEM70 Deficiency: Long-Term Outcome of 48 Patients.” JOURNAL OF INHERITED METABOLIC DISEASE, vol. 38, no. 3, 2015, pp. 417–26, doi:10.1007/s10545-014-9774-8.
- APA
- Magner, M., Dvorakova, V., Tesarova, M., Mazurova, S., Hansikova, H., Zahorec, M., … Honzik, T. (2015). TMEM70 deficiency: long-term outcome of 48 patients. JOURNAL OF INHERITED METABOLIC DISEASE, 38(3), 417–426. https://doi.org/10.1007/s10545-014-9774-8
- Chicago author-date
- Magner, Martin, Veronika Dvorakova, Marketa Tesarova, Stella Mazurova, Hana Hansikova, Martin Zahorec, Katarina Brennerova, et al. 2015. “TMEM70 Deficiency: Long-Term Outcome of 48 Patients.” JOURNAL OF INHERITED METABOLIC DISEASE 38 (3): 417–26. https://doi.org/10.1007/s10545-014-9774-8.
- Chicago author-date (all authors)
- Magner, Martin, Veronika Dvorakova, Marketa Tesarova, Stella Mazurova, Hana Hansikova, Martin Zahorec, Katarina Brennerova, Vladimir Bzduch, Ronen Spiegel, Yoseph Horovitz, Hanna Mandel, Fatma Tuba Eminoğlu, Jhannes Adalbert Mayr, Johannes Koch, Diego Martinelli, Enrico Bertini, Vassiliki Konstantopoulou, Joél Smet, Shamima Rahman, Alexander Broomfield, Vesna Stojanović, Carlo Dionisi-Vici, Rudy Van Coster, Eva Morava, Wolgang Sperl, Jiri Zeman, and Tomas Honzik. 2015. “TMEM70 Deficiency: Long-Term Outcome of 48 Patients.” JOURNAL OF INHERITED METABOLIC DISEASE 38 (3): 417–426. doi:10.1007/s10545-014-9774-8.
- Vancouver
- 1.Magner M, Dvorakova V, Tesarova M, Mazurova S, Hansikova H, Zahorec M, et al. TMEM70 deficiency: long-term outcome of 48 patients. JOURNAL OF INHERITED METABOLIC DISEASE. 2015;38(3):417–26.
- IEEE
- [1]M. Magner et al., “TMEM70 deficiency: long-term outcome of 48 patients,” JOURNAL OF INHERITED METABOLIC DISEASE, vol. 38, no. 3, pp. 417–426, 2015.
@article{5745843, abstract = {{OBJECTIVES: TMEM70 deficiency is the most common nuclear-encoded defect affecting the ATP synthase. In this multicentre retrospective study we characterise the natural history of the disease, treatment and outcome in 48 patients with mutations in TMEM70. Eleven centers from eight European countries, Turkey and Israel participated. RESULTS: All 27 Roma and eight non-Roma patients were homozygous for the common mutation c.317-2A > G. Five patients were compound heterozygotes for the common mutation and mutations c.470 T > A, c.628A > C, c.118_119insGT or c.251delC. Six Arab Muslims and two Turkish patients were homozygous for mutations c.238C > T, c.316 + 1G > T, c.336 T > A, c.578_579delCA, c.535C > T, c.359delC. Age of onset was neonatal in 41 patients, infantile in six cases and two years in one child. The most frequent symptoms at onset were poor feeding, hypotonia, lethargy, respiratory and heart failure, accompanied by lactic acidosis, 3-methylglutaconic aciduria and hyperammonaemia. Symptoms further included: developmental delay (98 %), hypotonia (95 %), faltering growth (94 %), short stature (89 %), non-progressive cardiomyopathy (89 %), microcephaly (71 %), facial dysmorphism (66 %), hypospadias (50 % of the males), persistent pulmonary hypertension of the newborn (22 %) and Wolff-Parkinson-White syndrome (13 %). One or more acute metabolic crises occurred in 24 surviving children, frequently followed by developmental regression. Hyperammonaemic episodes responded well to infusion with glucose and lipid emulsion, and ammonia scavengers or haemodiafiltration. Ten-year survival was 63 %, importantly for prognostication, no child died after the age of five years. CONCLUSION: TMEM70 deficiency is a panethnic, multisystemic disease with variable outcome depending mainly on adequate management of hyperammonaemic crises in the neonatal period and early childhood.}}, author = {{Magner, Martin and Dvorakova, Veronika and Tesarova, Marketa and Mazurova, Stella and Hansikova, Hana and Zahorec, Martin and Brennerova, Katarina and Bzduch, Vladimir and Spiegel, Ronen and Horovitz, Yoseph and Mandel, Hanna and Eminoğlu, Fatma Tuba and Mayr, Jhannes Adalbert and Koch, Johannes and Martinelli, Diego and Bertini, Enrico and Konstantopoulou, Vassiliki and Smet, Joél and Rahman, Shamima and Broomfield, Alexander and Stojanović, Vesna and Dionisi-Vici, Carlo and Van Coster, Rudy and Morava, Eva and Sperl, Wolgang and Zeman, Jiri and Honzik, Tomas}}, issn = {{0141-8955}}, journal = {{JOURNAL OF INHERITED METABOLIC DISEASE}}, keywords = {{ATP SYNTHASE,MITOCHONDRIAL,BARTH-SYNDROME,3-METHYLGLUTACONIC ACIDURIA,ACUTE METABOLIC DECOMPENSATION,ACIDURIA TYPE-IV,MUTATION,GENES,CARDIOMYOPATHY,PROTEIN}}, language = {{eng}}, number = {{3}}, pages = {{417--426}}, title = {{TMEM70 deficiency: long-term outcome of 48 patients}}, url = {{http://doi.org/10.1007/s10545-014-9774-8}}, volume = {{38}}, year = {{2015}}, }
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