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. © 2014 The Authors.
Fraser, J. L., Vanderver, A., Yang, S., Chang, T., Cramp, L., Vezina, G., … Zand, D. J. (2014). 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, 1(1), 66–70. https://doi.org/10.1016/j.ymgmr.2013.12.007