Thiamine Deficiency: New Fads Old ProblemsShawn Reeves MSN, RN, CPNP – AC/PC 1,2, Clayton Womack MSN, RN, CPNP-AC 1,2, Sara Halfmann 1, M.D.

Thivakorn Kasemsri, M.D.1,2

1Department of Pediatrics, 2Division of Pediatric Critical Care MedicineTexas Tech University Health Sciences Center, Lubbock, TX

Thiamine is a water-soluble vitamin involved in many cellular metabolic activities which result in the production of ATP. The primary source of thiamine is from diet including whole grains, pork and legumes. Thiamine stores can be depleted in as little as 18 days resulting in inadequate ATP production that disrupts organ systems with high metabolic demands such as the cardiovascular and nervous systems. This depletion leads to the clinical presentations of wet and/or dry beriberi which rapidly progress without thiamine replacement. In extreme cases, beriberi is associated with Wernicke-Korsakoff syndrome which damages the thalamic and hypothalamic regions of the brain leading to confusion and visual problems.

Patient One:MRI findings were consistent with thiamine deficiency or a mitochondrial disorder such as Leigh disease.Suspected thiamine deficiency based on dietary history and clinical symptoms of Wernicke-Korsakoff syndrome.Treated empirically with thiamine with rapid and sustained improvement in neurologic symptoms.Metabolic workup for mitochondrial disorders was negative.Patient Two:Again due to clinical and dietary history thiamine deficiency was suspected.Treated with thiamine with rapid and sustained improvement in neurologic symptoms.Patient Three:Presented in acute respiratory failure secondary to viral etiology but appeared more severe than expected.The patient recovered and was discharged home without thiamine administration.Thiamine level returned after patient was discharged and pediatrician was notified of results.No follow-ups were completed as attempts to contact families failed.

Patient One:15-month old male who presented with encephalopathy and seizures

Patient Two:22-month old male who presented with seizure activity

Patient Three:13-month old female who presented with acute respiratory failure

Thiamine levels were tested in all three patients due to clinical symptoms and history.All patients presented with a history of almond milk consumption as the primary source of milk.All patients presented with Thiamine levels < 7 nmol/L (norm 74-222).

References:1. Vasconcelos, M. M., Silva, K. P., Vidal, G., Silva, A. F., Domingues, R. C., & Berditchevsky, C. R. (1999). Early diagnosis of pediatric wernicke’s encephalopathy. Pediatric Neurology, 20(4), 289-294. doi:10.1016/s0887-8994(98)00153-22. Thiamine deficiency and its prevention and control in major emergencies. (1999). Geneva: World Health Organization.3. Sechi, G., & Serra, A. (2007). Wernickes encephalopathy: new clinical settings and recent advances in diagnosis and management. The Lancet Neurology, 6(5), 442-455. doi:10.1016/s1474-4422(07)70104-74. Peters, T. E., Parvin, M., Petersen, C., Faircloth, V. C., & Levine, R. L. (2007). A Case Report of Wernicke’s Encephalopathy in a Pediatric Patient with Anorexia Nervosa - Restricting Type. Journal of Adolescent Health, 40(4), 376-383. doi:10.1016/j.jadohealth.2006.11.1405. Fattal-Valevski, A. (2005). Outbreak of Life-Threatening Thiamine Deficiency in Infants in Israel Caused by a Defective Soy-Based Formula. Pediatrics, 115(2). doi:10.1542/peds.2004-1255

Thiamine deficiency is uncommon in the United States and most western civilized cultures due to high prevalence of thiamine-containing foods.Infantile thiamine deficiency can be exhibited in 3 forms: cardiologic, aphonic or pseudo-meningiticforms. History of dietary fads may reflect a diet deficient in thiamine and testing should be considered in context of clinical manifestations. Biochemically, the measurement of erythrocyte transketolase activity (ETKA) and the thiamine pyrophosphate effect (TPPE), provide a sensitive thiamine deficiency test.Under recognition of thiamine deficiency can lead to severe neurological manifestations.Once thiamine replaced, full recovery is possible.

Thiamine condition TPPE

Normal 0-14%

Marginally deficient 15-24%

Severely deficient (clinical signs) 25+%

Figure 1. Patient One: Head MRI revealed a symmetric abnormal signal with restricted diffusion within the putamen and caudate nucleus with increased T2 signal in the bilateral thalami and periaqueductal white matter.

1 Shawn M. Reeves, MSN, APRN, CPNP-AC/PC; Lead UMC PICU NP, Division of Critical Care, Department of Pedatrics, Texas Tech University Health Sciences Center, Lubbock, TX 2 Clayton Womack, MSN, APRN, CPNP-AC; UMC PICU NP, Division of Critical Care, Department of Pedatrics, Texas Tech University Health Sciences Center, Lubbock, TX 3 Sara Halfmann, MD; Pediatric Resident, Department of Pedatrics, Texas Tech University Health Sciences Center, Lubbock, TX 4 Thivakorn Kasemsri, MD, MS; UMC PICU Medical Director, Critical Care Division Chief, Department of Pedatrics, Texas Tech University Health Sciences Center, Lubbock, TX Poster Number: W20

Thiamine Deficiency: New Fads Old Problems Abstract:

Thiamine is a water-soluble B1 vitamin involved in many cellular metabolic activities which result in the production of ATP. The primary source of thiamine is from the diet including whole grains, pork and legumes. Thiamine deficiency is uncommon in the United States and most western civilized cultures due to a high prevalence of thiamine-containing foods. Dietary stores can be depleted in as little as 18 days if not replaced, resulting in inadequate ATP production that significantly disrupts organ systems with high metabolic demands such as the cardiovascular and nervous systems, leading to the clinical presentations of wet and dry beriberi. In contrast, thiamine deficiency is more prevalent in areas of the world where the diet is comprised of polished rice products, vegetables and seafood which are poor sources of thiamine.

A case series is presented with a 15-month old male, 22-month old male, and 13-month old female. Each patient presented with severe metabolic or respiratory compromise. All patients presented with a history of almond milk consumption as the primary source of milk. Two presented with seizure activity while the third presented in respiratory failure. Thiamine levels were tested in all three patients due to clinical symptomology and history. Each patient saw a decreased thiamine level at <7 nmol/L (normal: 74-222 nmol/L). Thiamine administration was administered to two of the three patients with rapid reversal of symptoms. The third patient recovered prior to thiamine administration however the pediatrician was notified of the results.

Infantile thiamine deficiency exists in 3 forms: cardiologic, aphonic or pseudo-meningitic. Testing for this disease should be considered when there is a history of low thiamine diet or clinical manifestations. Recommended biochemical diagnosis include thiamine level (blood or urine), erythrocyte transketolase activity (ETKA) and thiamine pyrophosphate effect (TPPE). Due to the complex clinical presentation of thiamine deficiency and decreased prevalence in the developed world, this life-threatening disorder may be under recognized and easily missed. Once thiamine is replaced, symptoms rapidly improve, often leading to a full recovery. On the contrary, if thiamine deficiency is not recognized, patients can have severe neurologic damage while cardiac manifestations can lead to death.

The presentation of these patients reminds us that classical vitamin deficiencies can always make a comeback when food fads change rapidly even in developed economies It is important for pediatric providers to always explore diet history during well-checks in order to anticipate adverse events. Finally, we wonder if thiamine deficiency can make common viral illnesses more intense resulting in PICU admissions.

No funding was obtain in the development of this Case Study.