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Mercedes Serrano - One of the best experts on this subject based on the ideXlab platform.
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Thiamine transporter-2 deficiency: outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Darío Ortigoza-escobar, Monica Rebollo, Marta Molero, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Pilar Rodríguez-pombo, Belén Pérez-dueñasAbstract:Antecedentes Las características clínicas distintivas del déficit tratable del trasportador de tiamina tipo 2 (ThTR2) debido a defectos genéticos del SLC19A3 de las otras causas devastadores del síndrome de Leigh son escasas. Métodos Presentamos el seguimiento clínico después de la administración de suplementos de tiamina y biotina a cuatro niños con deficiencia ThTR2 que presentaban fenotipos de biotin-thiamine responsive Basal Ganglia Disease y síndrome de Leigh. Hemos establecido valores de referencia de tiamina en sangre total en 106 niños sin patología neurológica y monitorizamos los niveles de tiamina en pacientes con mutación del SLC19A3 después del inicio del tratamiento. Hemos comparado nuestros resultados con los de 69 pacientes con deficiencia ThTR2 después de una revisión de la literatura. Resultados Al momento del diagnóstico , los pacientes tenían entre 1 mes a 17 años, y todos ellos mostraron signos de encefalopatía aguda, distonía generalizada, y lesiones cerebrales que afectan el cuerpo estriado dorsal y el tálamo medial. Un paciente murió de septicemia, mientras que el resto de pacientes evidenciaron mejoras clínicas y radiológicas poco después del inicio de la tiamina. Al seguimiento, los pacientes recibieron una combinación de tiamina (10–40 mg/kg/día) y biotina (1–2 mg/kg/día) y se mantuvieron estables, aunque con distonía y dificultades del habla residual. Después de establecer valores de referencia para los diferentes grupos de edad, la cuantificación de tiamina en sangre total demuestra ser un método útil para el seguimiento del tratamiento. Conclusiones La deficiencia ThTR2 es una causa reversible de la distonía aguda y síndrome de Leigh en la edad pediátrica. Las lesiones cerebrales que afectan el cuerpo estriado dorsal y tálamo medial pueden ser útiles en el diagnóstico diferencial de otras causas de síndrome de Leigh. Se necesitan más estudios para validar las dosis de tiamina y la monitorización terapéutica de estos pacientes. Background The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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thiamine transporter 2 deficiency outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Dario Ortigozaescobar, Monica Rebollo, Marta Molero, Pilar Rodriguezpombo, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Belen PerezduenasAbstract:Background: The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods: We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results: At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions: ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency
Movement Disorders, 2012Co-Authors: Monica Rebollo, Agnes Rastetter, Emilio Fernandezalvarez, Christel Depienne, Mercedes Serrano, Jordi Muchart, Loreto Martorell, Rafael ArtuchAbstract:Background: Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive Basal Ganglia Disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Methods: Two Spanish siblings with a biotin-responsive Basal Ganglia Disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. Results: The clinical features resolved rapidly after thiamine administration. Conclusions: Despite the rarity of thiamine transporter–2 deficiency, it should be suspected in patients with acute dystonia and Basal Ganglia injury, as thiamine can halt Disease evolution and prevent further episodes. © 2012 Movement Disorder Society
Rafael Artuch - One of the best experts on this subject based on the ideXlab platform.
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Thiamine transporter-2 deficiency: outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Darío Ortigoza-escobar, Monica Rebollo, Marta Molero, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Pilar Rodríguez-pombo, Belén Pérez-dueñasAbstract:Antecedentes Las características clínicas distintivas del déficit tratable del trasportador de tiamina tipo 2 (ThTR2) debido a defectos genéticos del SLC19A3 de las otras causas devastadores del síndrome de Leigh son escasas. Métodos Presentamos el seguimiento clínico después de la administración de suplementos de tiamina y biotina a cuatro niños con deficiencia ThTR2 que presentaban fenotipos de biotin-thiamine responsive Basal Ganglia Disease y síndrome de Leigh. Hemos establecido valores de referencia de tiamina en sangre total en 106 niños sin patología neurológica y monitorizamos los niveles de tiamina en pacientes con mutación del SLC19A3 después del inicio del tratamiento. Hemos comparado nuestros resultados con los de 69 pacientes con deficiencia ThTR2 después de una revisión de la literatura. Resultados Al momento del diagnóstico , los pacientes tenían entre 1 mes a 17 años, y todos ellos mostraron signos de encefalopatía aguda, distonía generalizada, y lesiones cerebrales que afectan el cuerpo estriado dorsal y el tálamo medial. Un paciente murió de septicemia, mientras que el resto de pacientes evidenciaron mejoras clínicas y radiológicas poco después del inicio de la tiamina. Al seguimiento, los pacientes recibieron una combinación de tiamina (10–40 mg/kg/día) y biotina (1–2 mg/kg/día) y se mantuvieron estables, aunque con distonía y dificultades del habla residual. Después de establecer valores de referencia para los diferentes grupos de edad, la cuantificación de tiamina en sangre total demuestra ser un método útil para el seguimiento del tratamiento. Conclusiones La deficiencia ThTR2 es una causa reversible de la distonía aguda y síndrome de Leigh en la edad pediátrica. Las lesiones cerebrales que afectan el cuerpo estriado dorsal y tálamo medial pueden ser útiles en el diagnóstico diferencial de otras causas de síndrome de Leigh. Se necesitan más estudios para validar las dosis de tiamina y la monitorización terapéutica de estos pacientes. Background The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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thiamine transporter 2 deficiency outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Dario Ortigozaescobar, Monica Rebollo, Marta Molero, Pilar Rodriguezpombo, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Belen PerezduenasAbstract:Background: The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods: We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results: At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions: ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency
Movement Disorders, 2012Co-Authors: Monica Rebollo, Agnes Rastetter, Emilio Fernandezalvarez, Christel Depienne, Mercedes Serrano, Jordi Muchart, Loreto Martorell, Rafael ArtuchAbstract:Background: Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive Basal Ganglia Disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Methods: Two Spanish siblings with a biotin-responsive Basal Ganglia Disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. Results: The clinical features resolved rapidly after thiamine administration. Conclusions: Despite the rarity of thiamine transporter–2 deficiency, it should be suspected in patients with acute dystonia and Basal Ganglia injury, as thiamine can halt Disease evolution and prevent further episodes. © 2012 Movement Disorder Society
Monica Rebollo - One of the best experts on this subject based on the ideXlab platform.
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Thiamine transporter-2 deficiency: outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Darío Ortigoza-escobar, Monica Rebollo, Marta Molero, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Pilar Rodríguez-pombo, Belén Pérez-dueñasAbstract:Antecedentes Las características clínicas distintivas del déficit tratable del trasportador de tiamina tipo 2 (ThTR2) debido a defectos genéticos del SLC19A3 de las otras causas devastadores del síndrome de Leigh son escasas. Métodos Presentamos el seguimiento clínico después de la administración de suplementos de tiamina y biotina a cuatro niños con deficiencia ThTR2 que presentaban fenotipos de biotin-thiamine responsive Basal Ganglia Disease y síndrome de Leigh. Hemos establecido valores de referencia de tiamina en sangre total en 106 niños sin patología neurológica y monitorizamos los niveles de tiamina en pacientes con mutación del SLC19A3 después del inicio del tratamiento. Hemos comparado nuestros resultados con los de 69 pacientes con deficiencia ThTR2 después de una revisión de la literatura. Resultados Al momento del diagnóstico , los pacientes tenían entre 1 mes a 17 años, y todos ellos mostraron signos de encefalopatía aguda, distonía generalizada, y lesiones cerebrales que afectan el cuerpo estriado dorsal y el tálamo medial. Un paciente murió de septicemia, mientras que el resto de pacientes evidenciaron mejoras clínicas y radiológicas poco después del inicio de la tiamina. Al seguimiento, los pacientes recibieron una combinación de tiamina (10–40 mg/kg/día) y biotina (1–2 mg/kg/día) y se mantuvieron estables, aunque con distonía y dificultades del habla residual. Después de establecer valores de referencia para los diferentes grupos de edad, la cuantificación de tiamina en sangre total demuestra ser un método útil para el seguimiento del tratamiento. Conclusiones La deficiencia ThTR2 es una causa reversible de la distonía aguda y síndrome de Leigh en la edad pediátrica. Las lesiones cerebrales que afectan el cuerpo estriado dorsal y tálamo medial pueden ser útiles en el diagnóstico diferencial de otras causas de síndrome de Leigh. Se necesitan más estudios para validar las dosis de tiamina y la monitorización terapéutica de estos pacientes. Background The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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thiamine transporter 2 deficiency outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Dario Ortigozaescobar, Monica Rebollo, Marta Molero, Pilar Rodriguezpombo, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Belen PerezduenasAbstract:Background: The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods: We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results: At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions: ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency
Movement Disorders, 2012Co-Authors: Monica Rebollo, Agnes Rastetter, Emilio Fernandezalvarez, Christel Depienne, Mercedes Serrano, Jordi Muchart, Loreto Martorell, Rafael ArtuchAbstract:Background: Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive Basal Ganglia Disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Methods: Two Spanish siblings with a biotin-responsive Basal Ganglia Disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. Results: The clinical features resolved rapidly after thiamine administration. Conclusions: Despite the rarity of thiamine transporter–2 deficiency, it should be suspected in patients with acute dystonia and Basal Ganglia injury, as thiamine can halt Disease evolution and prevent further episodes. © 2012 Movement Disorder Society
Jordi Muchart - One of the best experts on this subject based on the ideXlab platform.
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Thiamine transporter-2 deficiency: outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Darío Ortigoza-escobar, Monica Rebollo, Marta Molero, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Pilar Rodríguez-pombo, Belén Pérez-dueñasAbstract:Antecedentes Las características clínicas distintivas del déficit tratable del trasportador de tiamina tipo 2 (ThTR2) debido a defectos genéticos del SLC19A3 de las otras causas devastadores del síndrome de Leigh son escasas. Métodos Presentamos el seguimiento clínico después de la administración de suplementos de tiamina y biotina a cuatro niños con deficiencia ThTR2 que presentaban fenotipos de biotin-thiamine responsive Basal Ganglia Disease y síndrome de Leigh. Hemos establecido valores de referencia de tiamina en sangre total en 106 niños sin patología neurológica y monitorizamos los niveles de tiamina en pacientes con mutación del SLC19A3 después del inicio del tratamiento. Hemos comparado nuestros resultados con los de 69 pacientes con deficiencia ThTR2 después de una revisión de la literatura. Resultados Al momento del diagnóstico , los pacientes tenían entre 1 mes a 17 años, y todos ellos mostraron signos de encefalopatía aguda, distonía generalizada, y lesiones cerebrales que afectan el cuerpo estriado dorsal y el tálamo medial. Un paciente murió de septicemia, mientras que el resto de pacientes evidenciaron mejoras clínicas y radiológicas poco después del inicio de la tiamina. Al seguimiento, los pacientes recibieron una combinación de tiamina (10–40 mg/kg/día) y biotina (1–2 mg/kg/día) y se mantuvieron estables, aunque con distonía y dificultades del habla residual. Después de establecer valores de referencia para los diferentes grupos de edad, la cuantificación de tiamina en sangre total demuestra ser un método útil para el seguimiento del tratamiento. Conclusiones La deficiencia ThTR2 es una causa reversible de la distonía aguda y síndrome de Leigh en la edad pediátrica. Las lesiones cerebrales que afectan el cuerpo estriado dorsal y tálamo medial pueden ser útiles en el diagnóstico diferencial de otras causas de síndrome de Leigh. Se necesitan más estudios para validar las dosis de tiamina y la monitorización terapéutica de estos pacientes. Background The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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thiamine transporter 2 deficiency outcome and treatment monitoring
Orphanet Journal of Rare Diseases, 2014Co-Authors: Juan Dario Ortigozaescobar, Monica Rebollo, Marta Molero, Pilar Rodriguezpombo, Mercedes Serrano, Jordi Muchart, Alfonso Oyarzabal, Rafael Artuch, Belen PerezduenasAbstract:Background: The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods: We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive Basal Ganglia Disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results: At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions: ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
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reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency
Movement Disorders, 2012Co-Authors: Monica Rebollo, Agnes Rastetter, Emilio Fernandezalvarez, Christel Depienne, Mercedes Serrano, Jordi Muchart, Loreto Martorell, Rafael ArtuchAbstract:Background: Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive Basal Ganglia Disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Methods: Two Spanish siblings with a biotin-responsive Basal Ganglia Disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. Results: The clinical features resolved rapidly after thiamine administration. Conclusions: Despite the rarity of thiamine transporter–2 deficiency, it should be suspected in patients with acute dystonia and Basal Ganglia injury, as thiamine can halt Disease evolution and prevent further episodes. © 2012 Movement Disorder Society
Christel Depienne - One of the best experts on this subject based on the ideXlab platform.
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reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency
Movement Disorders, 2012Co-Authors: Monica Rebollo, Agnes Rastetter, Emilio Fernandezalvarez, Christel Depienne, Mercedes Serrano, Jordi Muchart, Loreto Martorell, Rafael ArtuchAbstract:Background: Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive Basal Ganglia Disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Methods: Two Spanish siblings with a biotin-responsive Basal Ganglia Disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. Results: The clinical features resolved rapidly after thiamine administration. Conclusions: Despite the rarity of thiamine transporter–2 deficiency, it should be suspected in patients with acute dystonia and Basal Ganglia injury, as thiamine can halt Disease evolution and prevent further episodes. © 2012 Movement Disorder Society
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Biotin-Responsive Basal Ganglia Disease in Ethnic Europeans With Novel SLC19A3 Mutations
Archives of Neurology, 2010Co-Authors: Rabab Debs, Agnes Rastetter, Christel Depienne, Agnès Bellanger, Bertrand Degos, Damien Galanaud, Boris Keren, Olivier Lyon-caen, Alexis Brice, Frédéric SedelAbstract:OBJECTIVE: To report the first 2 European cases of biotin-responsive Basal Ganglia Disease and novel SLC19A3 mutations. DESIGN: Case reports. SETTING: University hospital. Patients A 33-year-old man and his 29-year-old sister, both of Portuguese ancestry, presented with recurrent episodes of encephalopathy. Between episodes patients exhibited generalized dystonia, epilepsy, and bilateral hyperintensities of the caudate and putamen. MAIN OUTCOME MEASURES: Clinical and radiologic findings. RESULTS: Administration of high doses of biotin or of a combination of biotin and thiamine during encephalopathies resulted in spectacular clinical and radiologic improvement in both patients. Sequencing of the SLC19A3 disclosed 2 novel mutations, both of which created premature stop codons in the protein sequence of hTHTR2. CONCLUSION: This study demonstrates that biotin-responsive Basal Ganglia Disease is a panethnic condition. A therapeutic trial with high doses of biotin and thiamine seems mandatory in every unexplained encephalopathy with bilateral lesions of putamen and caudate nuclei.
