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 Fraser, J. L., Vanderver, A., Yang, S., Chang, T., Cramp, L., Vezina, G., Lichter-Konecki, U., Cusmano-Ozog, K. P., Smpokou, P., Chapman, K. A., Zand, D. J. 2014; 1: 66-70


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, a-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.

View details for DOI 10.1016/j.ymgmr.2013.12.007

View details for PubMedID 27896076

View details for PubMedCentralID PMC5121315