Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs

Kyly C Whitfield, Megan W Bourassa, Bola Adamolekun, Gilles Bergeron, Lucien Bettendorff, Kenneth H Brown, Lorna Cox, Aviva Fattal-Valevski, Philip R Fischer, Elizabeth L Frank, Laurent Hiffler, Lwin Mar Hlaing, Maria Elena Jefferds, Hallie Kapner, Sengchanh Kounnavong, Maral P S Mousavi, Daniel E Roth, Maria-Nefeli Tsaloglou, Frank Wieringa, Gerald F Combs Jr, Kyly C Whitfield, Megan W Bourassa, Bola Adamolekun, Gilles Bergeron, Lucien Bettendorff, Kenneth H Brown, Lorna Cox, Aviva Fattal-Valevski, Philip R Fischer, Elizabeth L Frank, Laurent Hiffler, Lwin Mar Hlaing, Maria Elena Jefferds, Hallie Kapner, Sengchanh Kounnavong, Maral P S Mousavi, Daniel E Roth, Maria-Nefeli Tsaloglou, Frank Wieringa, Gerald F Combs Jr

Abstract

Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month-specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high-risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing.

Keywords: LMIC; beriberi; erythrocyte transketolase; nutrition; thiamine deficiency; thiamine diphosphate.

© 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

Figures

Figure 1
Figure 1
Thiamine diphosphate is a cofactor required for several metabolic processes, shown in bold text. Adapted from Thurnham.9
Figure 2
Figure 2
The three thiamine‐dependent enzymes and their role in the pathogenesis of cell death in thiamine deficiency. Adapted from Fattal‐Valevski.10 Dashed lines represent indirect pathways. ThDP, thiamine diphosphate.
Figure 3
Figure 3
The sequential reactions involved in the erythrocyte transketolase (ETK) assay.
Figure 4
Figure 4
Comparison of the erythrocyte ThDP assay and ETKAC values from medical and surgical patients who were determined to be at risk of thiamine deficiency (from Talwar et al.17). ThDP, thiamine diphosphate; ETKAC, erythrocyte transketolase activation coefficient.
Figure 5
Figure 5
Clinical spectrum of thiamine deficiency disorders. Adapted from the WHO, 1999.39
Figure 6
Figure 6
An example of a proposed case definition of thiamine deficiency disorder (TDD).
Figure 7
Figure 7
Clinical guidelines for empirical treatment of suspected thiamine deficiency disorders (TDDs). LMIC, low‐ and middle‐income countries; IDP, internally displaced person; TDD, thiamine deficiency disorder.
Figure 8
Figure 8
Map depicting countries where the estimated per capita availability of thiamine in the national food supply (as per food balance sheets) is below the recommended nutrient intake for men of 1.2 mg/day (in turquoise), and countries where rice or wheat flour fortification is in place to address low thiamine availability (in yellow). Countries where the estimated mean thiamine availability is greater than or equal to 1.2 mg/day are in gray.
Figure 9
Figure 9
Comparison of infant mortality rates by month of age in Cambodia based on DHS data. CDHS, Cambodian Demographic and Household Survey.
Figure 10
Figure 10
A proposed approach for assessing a country's risk of thiamine deficiency disorders (TDDs) and the actions the countries could consider taking to prevent or eliminate TDD cases.
Figure 11
Figure 11
Educational poster outlining common signs of infantile beriberi (in Khmer).

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