Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge

Abstract

In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children.

Keywords: beriberi; pediatric critical care; refeeding syndrome; thiamine; thiamine deficiency; thiamine transporters; tropical pediatrics; type B lactic acidosis.

Figure 1

Simplified overview of thiamine intracellular action: focus on coenzymatic functions. (A) Infant thiamine distribution with its three main target organs; (B) thiamine cellular metabolism with its main pools and thiamine-related metabolic pathways; (C) zooming boxes: (C₁) – cytosolic pentose phosphate pathways using transketolase, (C₂) – HIF-1 alternative routes, (C₃) – mitochondrial events; ThDP is a cofactor for PDH, α-KGDH and BCKD. Under hypoxia/pseudo-hypoxia HIF1-α upregulates PDK1 that in turn downregulates PDH. Abbreviations: BCKD, branched-chain ketoacid dehydrogenase complex; LDH, lactic dehydrogenase leading to Type B acidosis; PDH, pyruvate dehydrogenase complex; PDK1, pyruvate dehydrogenase kinase; α-KGDH, alpha-ketoglutarate dehydrogenase. ATP, adenosine triphosphate; BCAA, branched-chain amino acids; Glut transporter, glucose transporter; HIF, hypoxia-inducible factor, as a dimeric (α, β unit) transcriptional factor; KC, Krebs cycle; M-TPP-T, mitochondrial thiamine pyrophosphate transporter; OAA, oxaloacetate; Succ-CoA, succinyl-coenzyme A; ThDP (or TPP), thiamine diphosphate; α-KG: α-ketoglutarate. (B) Intracellular dotted arrows: alternative pathways for pyruvate–lactate axis and for HIF-1 during Hypoxia/pseudo-hypoxia (e.g., TD).