Thiamine beyond Beriberi

Introduction: In resource-abundant settings thiamine deficiency is usually limited to those on daily diuretics, alcohol use disorder, very restrictive diets, and post gastric bypass. Children are rarely affected. We present two cases highlighting other at-risk populations with unusual manifestations and potential dire consequences if unrecognized and untreated. Case Description: Case 1 is a 13-year-old with relapsed ALL post CAR Tcell therapy admitted after 4 weeks of poor dietary intake due to typhlitis and C diff infection, who suddenly developed a severe unexplained lactic acidosis. Recognizing the Warburg effect as the source of the lactic acidosis, lead to thiamine supplementation. Within three hours the lactate dropped from 19 to 3 mmol/L, TCO2 increased from 14 to 26 mmol/L, and the serum pH was 7.46. Unfortunately, a few weeks later the patient died of complications of ALL Case 2 is a 9-year-old with long-standing self-injurious behavior, vomiting, and restricted oral intake, who presented with altered mental status, hypertonia, hyperreflexia, and seizures, leading to intubation and anticonvulsant therapy. Initial laboratories showed AKI and serum sodium of 197 mmol/L. The FeNa of 0.13% and the urine osmolality of 1005 mOsm/kg support the diagnosis of functional AKI. The water deficit was estimated at 7 liters. The admit CK was 777 U/L but despite an initial downtrend, from day 4 onwards (when the serum Na was down by only 37 mmol/L) it steadily rose by 10.000 units/day, peaking at 136,900 U/L on day 9, and steadily dropping thereafter. Thiamine supplementation was started on day 6 following a brain MRI which showed diffusion restriction consistent with either extra pontine myelinolysis or Wernicke’s encephalopathy. Clinically the patient improved with inpatient rehab, but to communicate verbally they required an AAC. Discussion: The Warburg effect refers to a situation where thiamine deficiency prevents pyruvate entry into the oxidative phosphorylation cycle, staying in the cytosol where it is fermented to lactate. The second case underscores how thiamine deficiency impairs the generation of ATP, which in the myocyte is essential for muscle relaxation. An active calcium ATPase, returns calcium from the sarcoplasm to the sarcoplasmic reticulum, leading to relaxation. When contraction persists, rhabdomyolysis ensues. These cases remind us of the diverse and essential biochemical functions of thiamine manifesting as clinical conundrums.