Last reviewed: 5 Nov 2021
Last updated: 26 Aug 2020



History and exam

Key diagnostic factors

  • dermatitis
  • insomnia, depression, or memory loss
  • intermittent stupor
  • hallucinations or delirium
  • weakness
  • peripheral neuropathy
  • oppositional hypertonus or myoclonus
  • cogwheel rigidity
  • primitive reflexes
  • ataxia
  • nausea, vomiting, or diarrhea
  • glossitis, cheilitis, or stomatitis

Other diagnostic factors

  • fatigue
  • anxiety or paranoia
  • anorexia, weight loss, or cachexia
  • headache
  • vertigo
  • incontinence
  • constipation
  • heartburn
  • angular palpebritis

Risk factors

  • malnutrition
  • chronic alcohol use disorder
  • vitamin B2 (riboflavin) deficiency
  • vitamin B6 (pyridoxine) deficiency
  • malabsorption
  • eating disorders
  • Hartnup disease
  • carcinoid syndrome
  • antituberculous drugs
  • Crohn disease
  • HIV infection
  • copper deficiency
  • certain drugs
  • pregnancy and lactation
  • age >65 years
  • Alzheimer dementia
  • Parkinson disease

Diagnostic investigations

1st investigations to order

  • serum tryptophan
  • urinary N-methylnicotinamide
  • urinary N-methyl-2-pyridone-5-carboxamide
  • urinary 2-pyridone/N-methylnicotinamide ratio
  • skin biopsy
  • photosensitivity testing
  • CBC
  • serum albumin
  • serum protein
  • LFTs
  • gamma-GT

Investigations to consider

  • serum total iron
  • iron-binding capacity
  • ferritin
  • transketolase activity
  • thiamine pyrophosphate (TPP)
  • riboflavin coefficient
  • serum pyridoxal-5-phosphate
  • serum cyanocobalamin
  • serum folic acid
  • red cell folic acid
  • stool exam
  • neutral aminoaciduria
  • serum serotonin
  • platelet serotonin
  • urinary 5-hydroxyindoleacetic acid
  • HIV antibodies
  • mental state exam
  • ECG

Treatment algorithm



Whadi-ah Parker, PhD, RD(SA)

Senior Research Specialist

Centre for the Study of the Social and Environmental Determinants of Nutrition

Population Health, Health Systems and Innovation


Cape Town

South Africa


WP declares that she has no competing interests.

Zandile J Mchiza, RD, PhD


School of Public Health

University of the Western Cape

Cape Town

South Africa


ZJM declares that she has no competing interests.

Demetre Labadarios, MBChB, PhD, FACN

Professor Emeritus

Stellenbosch University

Professor Extraordinaire

University of Limpopo

South Africa


DL declares that he has no competing interests.


Dr Whadi-ah Parker, Dr Zandile J Mchiza, and Dr Demetre Labadarios would like to gratefully acknowledge Dr Nelia Patricia Steyn, a previous contributor, as well as Miss Nophiwe Job, Ms Nwabisa Tshefu, and Mr Machoene Derrick Sekgala for their contributions to this topic. NPS, NJ, NT, and MDS declare that they have no competing interests.

Peer reviewers

Alan Shenkin, MB, ChB, BSc, PhD, FRCP, FRCPath

Emeritus Professor of Clinical Chemistry

University of Liverpool



AS declares that he has no competing interests.

Alfredo Morabia, MD, PhD, MS


Queens College

City University of New York



AM declares that he has no competing interests.

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