Vitamin A Deficiency

Introduction

Vitamin A was the first fat-soluble vitamin to be discovered.
It comprises a family of compounds called the retinoids.
In nature, the active retinoids occur in 3
forms – Alcohol (retinol), aldehyde (retinal or retinaldehyde) and acid (retinoic acid).
In the human body, retinol is the predominant form, and 11-cis-retinol is the active form.
Retinol-binding protein (RBP) binds vitamin A and regulates its absorption and metabolism.
Vitamin A is essential for:

  • Vision (especially dark adaptation)
  • Immune response
  • Epithelial cell growth and repair
  • Bone growth
  • Reproduction
  • Maintenance of the surface linings of the eyes
  • Epithelial integrity of respiratory, urinary, and intestinal tracts
  • Embryonic development
  • Regulation of adult genes
  • It functions as an activator of gene expression by retinoid alpha-receptor transcription factor and ligand-dependent transcription
    factor

Deficiency of vitamin A is found among
malnourished children, the elderly, and
chronically ill populations in the United
States, but it is more prevalent in developing countries.
Among the first signs of vitamin A deficiency (VAD) are:

  • Abnormal dark adaptation
  • Dry skin and dry hair
  • Broken fingernails
  • Decreased resistance to infections

Epidemiology

An estimated 250 million children in
developing countries are at risk for vitamin deficiency syndromes
The most widely affected group includes
up to 10 million malnourished children who develop xerophthalmia and have an
increased risk of complications and death from measles.
Each year 250,000 – 500,000 children become blind because of VAD.
Improving the vitamin A status of children (aged 6- 59 months) with deficiencies can reduce rates of death from measles by 50%; from diarrhoea by 33%, and from of all of mortality by 23%

Pathophysiology

Vitamin A deficiency may be secondary to:

  • Decreased ingestion
  • Defective absorption and altered metabolism
  • Increased requirements

An adult liver can store up to a year’s reserve of vitamin A, whereas a child’s liver may have enough stores to last only several weeks
Serum retinol concentration reflects an individual’s vitamin A status.
Because serum retinol is homeostatically
controlled, its levels do not drop until the
body’s stores are significantly limited
The serum concentration of retinol is affected by several factors:

  • Synthesis of Retinol Binding Protein in the liver
  • Infection
  • Nutritional status:
  • Adequate levels of other nutrients such as zinc and iron

Recommended Daily Allowance

  • Infant (1 year or younger) 375 μg
  • Child 1-3 years 400 μg
  • Child 4-6 years 500 μg
  • Child 7-10 years 700 μg
  • All males older than 10 years 1000 μg
  • All females older than 10 years 800 μg

Aetiology

  • Malnutrition
    • The commonest cause of VAD in this part of the world
  • Inadequate intake
  • Measles infection
  • Increased risk of deficiency in:
    • Fat malabsorption
    • Cystic fibrosis
    • Tropical sprue
    • Pancreatic insufficiency
    • Inflammatory bowel disease
    • Cholestasis
    • Small bowel bypass surgery
    • Vegans
    • Refugees
    • Recent immigrants
    • Alcoholism
    • Toddlers and pre-school children living below the poverty line

Clinical features

  • VAD may be asymptomatic
  • Increased risk of respiratory and diarrhoeal infections
  • Decreased growth rate
  • Retarded bone development
  • Increased fatigue as a manifestation of VAD
  • Dry hair from blockage of hair follicles with plugs of anaemia
  • Bitot spots
  • Poor dark adaptation (nyctalopia)
  • Dry skin
  • Pruritus
  • Broken fingernails
  • Keratomalacia
  • Xerophthalmia
  • Follicular hyperkeratosis (phrynoderma)
  • keratin
  • Excessive deposition of periosteal bone secondary to reduced osteoclastic activity
  • Anaemia
  • Keratinization of mucous membranes

Differential diagnoses

  • Cataract
  • Refractive errors
  • Zinc deficiency

Complications

  • Blindness
  • Corneal ulceration

Investigations

Serum retinol

  • Costly but is a direct measure
  • A value of less than 0.7mg/L in children younger than 12 years is considered low

Serum RBP

  • Easier and less expensive to perform than retinol
  • Less accurate because levels are affected by serum protein concentrations; types of
    RBP cannot be differentiated

Serum zinc

  • Useful because zinc deficiency interferes with RBP production

Iron panel

  • Useful because iron deficiency can affect the metabolism of vitamin A

Serum albumin

  • Levels are indirect measures of levels of vitamin A

Full Blood Count with differentials

  • If anaemia, infection, or sepsis is a possibility

Serum electrolytes
Liver function tests

  • To evaluate nutritional status

Radiographs of the long bones

  • To evaluate bone growth and excessive deposition of periosteal bone

Clinical testing for dark-adaptation threshold

Treatment objectives

  • Reduce morbidity
  • Prevent complications
  • Treat complications

Non-drug treatment

Eat foods rich in vitamin A

  • Liver
  • Beef
  • Chicken
  • Eggs
  • Whole milk; fortified milk
  • Carrots
  • Mangoes
  • Orange fruits
  • Sweet potatoes
  • Spinach
  • Green vegetables

At least 5 servings of fruits and vegetables per day is recommended to provide a comprehensive distribution of carotenoids

Drug treatment

Daily oral supplements of vitamin A
Child:

  • Less than, or 3 years: 600 μg (2,000 IU) orally once daily
  • 4-8years: 900 μg (3,000 IU) orally once daily
  • 9-13years: 1,700 μg (5,665 IU) orally once daily
  • 14-18 years: 2,800 μg (9,335 IU) orally once daily

Adult:

  • all ages 3,000 μg (10,000 IU)
    orally once daily
  • Severe disease: 60,000 μg (200,000 IU) orally for a minimum of 2 days

Has been shown to reduce child mortality rates by 35-70%

Notable adverse drug reactions, caution

  • Risk of teratogenicity increases in pregnant women at doses >800 μg/day (not recommended at these doses)

Contraindicated in

  • Documented hypersensitivity
  • Hypervitaminosis A:

Parenteral vitamin A in infants of low birth weight may be associated with:

  • Thrombocytopenia
  • Renal dysfunction
  • Hepatomegaly
  • Ascites
  • Cholestasis
  • Metabolic acidosis (E-Ferol syndrome)
  • Hypotension

Prevention

  • Eat foods rich in vitamin A, in adequate amounts
  • Family and community health education