Last reviewed:September 2019
Last updated:December  2017



History and exam

Key diagnostic factors

  • vitamin C deficiency upon dietary review
  • constitutional symptoms
  • easy bruising or bleeding
  • gait impairment or leg pain
  • pedal edema
  • petechial and perifollicular hemorrhages (legs and feet)
  • poor wound healing
  • bruising and nodular or black ecchymoses at nontraumatic sites
  • joint swelling
  • oral mucosal petechiae
  • coiled hairs
  • follicular hyperkeratosis
  • tooth loss
  • gingival discoloration
  • gum swelling
  • lid petechiae and hemorrhages
  • proptosis
  • conjunctival and subconjunctival hemorrhage

Other diagnostic factors

  • dysphagia
  • alopecia
  • sicca-like or Sjogren-like syndrome
  • nail clubbing
  • peripheral (entrapment) neuropathy
  • CVA
  • CHF
  • hemorrhagic pleural effusion
  • osteoporosis

Risk factors

  • famine and refugee populations
  • older people
  • living alone
  • psychiatric disorders
  • alcoholism
  • dementia
  • low income
  • faddist diet
  • poor dentition or masticatory inefficiency
  • autistic spectrum disorder
  • static encephalopathies of childhood
  • infants taking only cow's milk
  • end stage renal disease and/or hemodialysis dependence
  • smoking
  • surgery
  • sepsis
  • HIV
  • critical illness
  • ARDS
  • pancreatitis
  • graft versus host disease (GVHD)

Diagnostic investigations

1st investigations to order

  • CBC and peripheral blood smear
  • serum ascorbic acid
  • leukocyte ascorbic acid
  • whole blood ascorbic acid
  • x-ray of knee and wrist
Full details

Investigations to consider

  • MRI of knee, wrists, and long bones in pediatric cases
  • bone marrow biopsy
Full details

Treatment algorithm


James M. Noble

Assistant Professor of Neurology

Columbia University Medical Center

Department of Neurology

Taub Institute for Research on Alzheimer’s Disease and the Aging Brain

G.H. Sergievsky Center

Columbia University

New York



JMN declares that he has no competing interests.

Marc C. Patterson


Division of Child and Adolescent Neurology

Professor of Neurology, Pediatrics, and Medical Genetics


Child Neurology Training Program

Mayo Clinic




MCP declares that he has received consultancy fees from Actelion, Alexion, Agios, Novartis, Orphazyme, Shire, and Vtesse; travel and accommodation expenses from Actelion, Alexion, Agios, and Shire; a grant from Actelion; honoraria from Journal of Child Neurology/Child Neurology Open and Journal of Inherited Metabolic Disease; and royalties from Up-to-Date.

Peer reviewersVIEW ALL


Molecular and Clinical Nutrition Section

Digestive Diseases Branch

National Institute of Diabetes and Digestive and Kidney Diseases




SP declares that he has no competing interests.

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