Mitochondrial Disorders Should Be Considered as a Differential Diagnosis of Thiamine Deficiency

Abstract

Description

This letter to the editor addresses limitations to diagnosing thiamine deficiency for multisystem disorders and discusses the potential differential diagnoses that must be considered.

Introduction

We read with interest the article by Meckley et al about a 45-year-old previously healthy woman who was admitted for recurrent nausea and vomiting for over 2 months, had an altered mental status, renal insufficiency, gastroparesis, and lower limb paraparesis, and was eventually diagnosed with probable thiamine deficiency.¹ The patient made an incomplete recovery with thiamine supplementation. The study is excellent, but several points should be discussed.

The first point is that the diagnosis of “probable thiamine deficiency” remains questionable. ¹ Since the serum thiamine level was not measured in the index patient, the diagnosis remains unsupported and was based only on the clinical picture and partial recovery under thiamine supplementation. However, a thiamine deficiency should only be diagnosed if a low thiamine serum level is detected and not on suspicion.

The second point is that several differential diagnoses were not considered and were not adequately ruled out. The first differential diagnosis that has not been adequately ruled out is a mitochondrial disorder, in particular, mitochondrial encephalopathy, lactic acidosis, stroke-like syndrome, and myo-neuro-gastrointestinal encephalopathy. In favor of mitochondrial disorder are steatosis without alcoholism, hepatitis or drug intoxication, short stature, lactic acidosis, renal cysts, renal insufficiency, nephrolithiasis, elevated pancreatic enzymes, recurrent vomiting, gastroparesis, and paraparesis of the lower limbs. A further argument in favor of mitochondrial disorder is the positive effect of thiamine and folic acid, a cocktail that is often administered to mitochondrial disorder patients and which has a positive effect. To rule out or diagnose mitochondrial disorder, it would have been mandatory to also perform magnetic resonance spectroscopy, nerve conduction studies, electromyography, a lactate stress test, and a muscle biopsy or genetic testing. A second differential diagnosis that could not be ruled out is autoimmune encephalitis. Therefore, a paraneoplastic serum and cerebrospinal fluid examination should be carried out, especially if a cerebrospinal fluid protein is elevated.

The third point is that a SARS-CoV-2 infection cannot be completely ruled out as the cause of the clinical picture. Since the patient was obviously admitted during the COVID-19 pandemic, a SARS-CoV-2 infection must be ruled out. What was the result of the reverse transcription polymerase chain reaction on admission? What was the vaccination status of the index patient?

The fourth point is that the patient was not followed up until full recovery. Long-term follow-up was needed to assess whether thiamine supplementation has truly led to full recovery. Different symptoms may require different times to recovery. In this respect, it is quite unlikely that the paraparesis resolved within a short period of time on thiamine.

The fifth point is that pancreatitis could not be sufficiently excluded. Since the lipase was elevated, it was essential to rule out pancreatitis by an abdominal ultrasonography or abdominal computed tomography.

The sixth point is that the patient presented with metabolic acidosis, but given the chronic vomiting, one would instead expect metabolic alkalosis. How can this discrepancy be explained?

Conclusion

This interesting case has limitations that put the results and their interpretation into perspective. Addressing these limitations could strengthen the conclusions and support the study's message. Thiamine deficiency can only be diagnosed by detecting low serum thiamine levels. Before attributing multisystem involvement to thiamine deficiency, all alternative differential diagnoses must be thoroughly ruled out.