Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies
We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ket...
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Elsevier
2014-01-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426914000147 |
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doaj-8721ed92ba104616bb40317896b771f52020-11-24T22:39:47ZengElsevierMolecular Genetics and Metabolism Reports2214-42692014-01-011C667010.1016/j.ymgmr.2013.12.007Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategiesJamie L. Fraser0Adeline Vanderver1Sandra Yang2Taeun Chang3Laura Cramp4Gilbert Vezina5Uta Lichter-Konecki6Kristina P. Cusmano-Ozog7Patroula Smpokou8Kimberly A. Chapman9Dina J. Zand10Pediatrics Residency Program, Children's National Medical Center, Washington, DC, USADivision of Neurology, Children's National Medical Center, Washington, DC, USADivision of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USADivision of Neurology, Children's National Medical Center, Washington, DC, USADivision of Neurology, Children's National Medical Center, Washington, DC, USADepartment of Radiology, Children's National Medical Center, Washington, DC, USADivision of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USADivision of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USADivision of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USADivision of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USADivision of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USAWe present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of previously lost milestones. The diagnosis of TPK deficiency was difficult due to inconsistent biochemical and diagnostic parameters, rapidity of clinical demise and would not have been made in a timely manner without the use of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary modification with cofactor supplementation which resulted in an improved clinical course.http://www.sciencedirect.com/science/article/pii/S2214426914000147Thiamine pyrophosphokinaseLeigh-like diseaseα-KetoglutarateThiamineMitochondrial disorder |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jamie L. Fraser Adeline Vanderver Sandra Yang Taeun Chang Laura Cramp Gilbert Vezina Uta Lichter-Konecki Kristina P. Cusmano-Ozog Patroula Smpokou Kimberly A. Chapman Dina J. Zand |
| spellingShingle |
Jamie L. Fraser Adeline Vanderver Sandra Yang Taeun Chang Laura Cramp Gilbert Vezina Uta Lichter-Konecki Kristina P. Cusmano-Ozog Patroula Smpokou Kimberly A. Chapman Dina J. Zand Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies Molecular Genetics and Metabolism Reports Thiamine pyrophosphokinase Leigh-like disease α-Ketoglutarate Thiamine Mitochondrial disorder |
| author_facet |
Jamie L. Fraser Adeline Vanderver Sandra Yang Taeun Chang Laura Cramp Gilbert Vezina Uta Lichter-Konecki Kristina P. Cusmano-Ozog Patroula Smpokou Kimberly A. Chapman Dina J. Zand |
| author_sort |
Jamie L. Fraser |
| title |
Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies |
| title_short |
Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies |
| title_full |
Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies |
| title_fullStr |
Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies |
| title_full_unstemmed |
Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies |
| title_sort |
thiamine pyrophosphokinase deficiency causes a leigh disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies |
| publisher |
Elsevier |
| series |
Molecular Genetics and Metabolism Reports |
| issn |
2214-4269 |
| publishDate |
2014-01-01 |
| description |
We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of previously lost milestones. The diagnosis of TPK deficiency was difficult due to inconsistent biochemical and diagnostic parameters, rapidity of clinical demise and would not have been made in a timely manner without the use of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary modification with cofactor supplementation which resulted in an improved clinical course. |
| topic |
Thiamine pyrophosphokinase Leigh-like disease α-Ketoglutarate Thiamine Mitochondrial disorder |
| url |
http://www.sciencedirect.com/science/article/pii/S2214426914000147 |
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