Synonyms: hypovitaminosis A

Vitamin A was the first vitamin identified (McCollum, Davis, 1915) and hence given the first letter in the alphabet. Vitamin A (retinol) is a fat-soluble vitamin, present in liver, milk and eggs.

Beta-carotene and other provitamin carotenoids occur in green leafy and orange/yellow vegetables and fruits. They are converted to retinal by small intestine mucosal cells, reduced to retinol, then esterified and stored in the liver (as retinyl palmitate). Vitamin A is transferred round the body as retinol bound to retinol-binding protein and prealbumin (transthyretin). Retinol is converted to rhodopsin (photoreceptor pigment) in the retina, and is also used to regulate gene expression and guide differentiation in a variety of other tissues.¹

Primary vitamin A deficiency

• This is caused by prolonged dietary deficiency, particularly where rice is the staple food (doesn't contain carotene).
• Vitamin A deficiency occurs with protein-energy malnutrition (marasmus or kwashiorkor) mainly because of dietary deficiency (but vitamin A storage and transport are also impaired).

Secondary vitamin A deficiency

• This occurs where there are problems in converting carotene to vitamin A, or reduced absorption, storage, or transport of vitamin A.
• This occurs in coeliac disease, tropical sprue, giardiasis, cystic fibrosis, other pancreatic disease, cirrhosis, duodenal bypass surgery, and bile duct obstruction.

Epidemiology

• it is rare in the UK,² but is extremely common in developing countries, especially Africa, Asia and the Western Pacific.
• Between 100 and 140 million children are vitamin A deficient; 250,000-500,000 of these children become blind every year and half of these die within 12 months of losing their sight.
• In pregnant women, vitamin A deficiency occurs especially in the last trimester (demand by fetus and mother is highest).³
• Other risk factors for vitamin A deficiency include:⁴
  • Fat malabsorption, cholestasis, inflammatory bowel disease, cystic fibrosis, pancreatic insufficiency or following small-bowel bypass surgery.
  • Vegan diet.
  • Alcoholism.
  • Toddlers and preschool children living below the poverty line.
  • Recent immigrants or refugees from developing countries.

Presentation⁴

Mild forms of vitamin A deficiency may cause no symptoms. However, there may still be an increased risk of developing respiratory infections and gastroenteritis, and delayed growth and bone development. There is also a risk of infertility secondary to impaired spermatogenesis, and an increased risk of miscarriage. Fatigue may present as a consequence of vitamin A deficiency anaemia.

• Eye and vision: pathognomonic changes occur in the eye (usually bilateral, although may be of differing degrees):
  • Poor adaptation to darkness - night blindness.
  • Keratomalacia (thinning and ultimately ulceration of the cornea - colliquative necrosis).
  • Conjunctival dryness, corneal dryness, xerophthalmia.
  • Bitot's spots (areas of abnormal squamous cell proliferation and keratinisation of the conjunctiva, causing oval, triangular or irregular foamy patches on the white of the eye).²
  • Corneal perforation.
  • Blindness due to structural damage to the retina.
• Skin and hair:
  • Dry skin, dry hair, pruritus.
  • Broken fingernails.
  • Follicular hyperkeratosis secondary to blockage of hair follicles, with plugs of keratin.
• Other less specific changes include:
  • Keratinisation of mucous membranes.
  • Increased susceptibility to infection (due to impairment of the humoral and cell-mediated immunity).
  • Skin changes (follicular hyperkeratosis) are also common.

Investigations⁴

• Serum retinol study is costly. Serum retinol-binding protein study is easier to perform and less expensive.
• Zinc level (zinc deficiency interferes with production of retinol-binding protein).
• Iron studies (iron deficiency can affect the metabolism of vitamin A).
• FBC: anaemia and infection may occur.
• Renal function tests, electrolytes and LFTs to evaluate for nutritional and hydration status.
• In children, X-rays of the long bones may be useful to evaluate bone growth and for excessive deposition of periosteal bone.
• Dark-adaptation threshold should be tested.

Differential diagnosis⁴

• Hypothyroidism
• Zinc deficiency

Management

• Treatment for subclinical vitamin A deficiency includes the consumption of vitamin A-rich foods - for example, liver, beef, chicken, eggs, fortified milk, carrots, mangoes, sweet potatoes and leafy green vegetables.⁴
• Good animal sources of vitamin A include liver, egg yolks, whole milk, animal butter and whole small fish (with liver intact).
• Animal sources, including vitamin A in breast milk, are more bioavailable than vegetable sources, which include carrots and other orange/yellow fruits and vegetables, and dark green leafy vegetables.³

Drugs

• For clinically evident vitamin A deficiency, treatment includes daily oral vitamin A supplements:⁴
  • Children aged 3 years or younger - 600 micrograms (2,000 IU).
  • Children aged 4-8 years - 900 micrograms (3,000 IU).
  • Children aged 9-13 years - 1,700 micrograms (5,665 IU).
  • Children aged 14-18 years - 2,800 micrograms (9,335 IU).
  • All adults - 3,000 micrograms (10,000 IU).
  • Therapeutic doses for severe disease include 60,000 micrograms (200,000 IU), which have been shown to reduce child mortality rates by 35-70%.
• Massive overdose of vitamin A can cause rough skin, dry hair, an enlarged liver, and a raised erythrocyte sedimentation rate and raised serum calcium and serum alkaline phosphatase concentrations.⁵
• In view of evidence suggesting that high levels of vitamin A may cause birth defects, women who are (or may become) pregnant are advised neither to take vitamin A supplements (including tablets and fish-liver oil drops), except on medical advice, nor to eat liver or products such as liver paté or liver sausage.⁵

Prognosis

Prognosis is good if patients are treated when the deficiency is subclinical. Morbidity increases once blindness has progressed. Irreversible conditions include punctate keratopathy, keratomalacia, and corneal perforation.⁴

• For patients with early mild eye problems, prompt treatment can result in full preservation of sight without residual impairment (heals completely within a few weeks).
• In the developing world, because a severe degree of vitamin A deficiency is often accompanied by severe generalised malnutrition, death is the most likely outcome. Mortality in infants with severe vitamin A deficiency is up to 50%.
• Only about 40% of patients with corneal xerophthalmia are alive one year later (25% are totally blind, and the remainder partially blind).

Prevention⁴

• Liver, beef, chicken, eggs, whole milk, fortified milk, carrots, mangoes, orange fruits, sweet potatoes, spinach, kale, and other green vegetables are among foods rich in vitamin A.
• Eating at least 5 servings of fruits and vegetables per day is recommended in order to provide a comprehensive distribution of carotenoids.
• A variety of foods, such as breakfast cereals, pastries, breads, crackers, and cereal grain bars, are often fortified with vitamin A.

Document references

1. Vitamin A Deficiency, Merck Manual
2. Ramsay A, Sabrosa NA, Pavesio CE; Bitot's spots and vitamin A deficiency in a child from the UK.; Br J Ophthalmol. 2001 Mar;85(3):372.
3. Vitamin and mineral requirements in human nutrition, Second edition, World Health Organization (WHO), 2004
4. Ansstas G et al, Vitamin A Deficiency, eMedicine, Dec 2010
5. British National Formulary; 60th Edition (September 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)

Internet and further reading

• Vitamin A Deficiency, World Health Organization (WHO)
• Sight and Life - Combating Vit A Deficiency

Acknowledgements