TY - JOUR
T1 - Thiamine Deficiency in Childhood with Attention to Genetic Causes
T2 - Survival and Outcome Predictors
AU - Ortigoza-Escobar, Juan Dario
AU - Alfadhel, Majid
AU - Molero-Luis, Marta
AU - Darin, Niklas
AU - Spiegel, Ronen
AU - de Coo, Irenaeus F.
AU - Gerards, Mike
AU - Taylor, Robert W.
AU - Artuch, Rafael
AU - Nashabat, Marwan
AU - Rodriguez-Pombo, Pilar
AU - Tabarki, Brahim
AU - Perez-Duenas, Belen
AU - Thiamine Deficiency Study Grp
PY - 2017/9
Y1 - 2017/9
N2 - Primary and secondary conditions leading to thiamine deficiency have overlapping features in children, presenting with acute episodes of encephalopathy, bilateral symmetric brain lesions, and high excretion of organic acids that are specific of thiamine-dependent mitochondrial enzymes, mainly lactate, alpha-ketoglutarate, and branched chain keto-acids. Undiagnosed and untreated thiamine deficiencies are often fatal or lead to severe sequelae. Herein, we describe the clinical and genetic characterization of 79 patients with inherited thiamine defects causing encephalopathy in childhood, identifying outcome predictors in patients with pathogenic SLC19A3 variants, the most common genetic etiology. We propose diagnostic criteria that will aid clinicians to establish a faster and accurate diagnosis so that early vitamin supplementation is considered.
AB - Primary and secondary conditions leading to thiamine deficiency have overlapping features in children, presenting with acute episodes of encephalopathy, bilateral symmetric brain lesions, and high excretion of organic acids that are specific of thiamine-dependent mitochondrial enzymes, mainly lactate, alpha-ketoglutarate, and branched chain keto-acids. Undiagnosed and untreated thiamine deficiencies are often fatal or lead to severe sequelae. Herein, we describe the clinical and genetic characterization of 79 patients with inherited thiamine defects causing encephalopathy in childhood, identifying outcome predictors in patients with pathogenic SLC19A3 variants, the most common genetic etiology. We propose diagnostic criteria that will aid clinicians to establish a faster and accurate diagnosis so that early vitamin supplementation is considered.
KW - BASAL GANGLIA DISEASE
KW - EXOME SEQUENCING REVEALS
KW - WERNICKE ENCEPHALOPATHY
KW - LEIGH-SYNDROME
KW - TRANSPORTER-2 DEFICIENCY
KW - PYROPHOSPHOKINASE DEFICIENCY
KW - MITOCHONDRIAL DISEASE
KW - CELL TRANSPLANTATION
KW - AUTISTIC-CHILD
KW - BIOTIN
U2 - 10.1002/ana.24998
DO - 10.1002/ana.24998
M3 - Article
SN - 0364-5134
VL - 82
SP - 317
EP - 330
JO - Annals of Neurology
JF - Annals of Neurology
IS - 3
ER -