Night blindness or nyctalopia, in which the eyes have difficulty in adjusting to dark is one of the earliest and common symptoms of VAD. Some young children may present with small, irregular patches of keratinization, called Bitot spots, in the conjunctiva. Deficiency of vitamin A leads to a reduction in the amount of visual pigments in the eye. Lack of pigments like rhodopsin and iodopsin affects transduction of light leading to poor vision and blindness. Drying of conjunctiva and cornea causes xerophthalmia which may be followed by progressive softening and thinning of the cornea called keratomalacia. If left untreated, it may result in infection and rupture of cornea. This degenerative change is yet another reason for blindness.

People deficient in vitamin A may also have dry hair and skin, and brittle nails. Malnutrition leads to follicular hyperkeratosis or phrynoderma, manifested by the presence of skin lesions and hyperkeratotic papules. These are often found in shoulders, buttocks and extremities. VAD increases the chance of infections by impairing the humoral and cell-mediated immunity. In some cases, keratinization of mucous membranes and deposition of periosteal bone may also be noted.

• Anemia

  INTRODUCTION: Micronutrient deficiency is an unquestionable public health problem, specially anemia and vitamin A deficiency (VAD). [ncbi.nlm.nih.gov]

  Causes of vitamin deficiency anemias, also known as megaloblastic anemias, include: Folate deficiency anemia. Folate, also known as vitamin B-9, is a nutrient found mainly in fruits and leafy green vegetables. [mayoclinic.org]

  Vitamin A deficiency is associated with anemia, and there may be several mechanisms by which vitamin A deficiency could cause anemia, including impairment of iron metabolism, and immune dysfunction and associated anemia of infection [ 23 ]. [nutritionj.biomedcentral.com]

• Loss of Appetite

  Its deficiency leads to poor growth, loss of muscular control, loss of appetite, weakness and hairfall. Folic acid (Vitamin B10) is essential for formation of RBC, and it also increases the appetite. [compete.etutor.co]

  Overconsumption of vitamin A can lead to jaundice, nausea, loss of appetite, irritability, vomiting, and even hair loss. [healthaliciousness.com]

• Jaundice

  Diseases such as obstructive jaundice or cystic fibrosis cause poor absorption of dietary fat and the fat-soluble vitamins. [health.howstuffworks.com]

  It can be due to sprue, celiac disease, obstructive jaundice, cirrhosis, giardiasis, cystic fibrosis or an over use of mineral oil as laxative. Over excretion of urine is also known to cause Vitamin A deficiency. [vitaminsall.com]

  Overconsumption of vitamin A can lead to jaundice, nausea, loss of appetite, irritability, vomiting, and even hair loss. [healthaliciousness.com]

• Muscle Weakness

  Vitamin E deficiencies generally manifest in polyneuropathy, which has symptoms of areflexia, cerebellar ataxia, loss of position sense, loss of vibration sense, and muscle weakness. [pharmacytimes.com]

  Symptoms and Health Risks of Vitamin D Deficiency Symptoms of bone pain and muscle weakness can mean you have a vitamin D deficiency. However, for many people, the symptoms are subtle. [webmd.com]

  Symptoms Signs and symptoms of vitamin deficiency anemia include: Fatigue Shortness of breath Dizziness Pale or yellowish skin Irregular heartbeats Weight loss Numbness or tingling in your hands and feet Muscle weakness Personality changes Unsteady movements [mayoclinic.org]

• Follicular Hyperkeratosis

  Phrynoderma is a rare form of follicular hyperkeratosis associated with deficiencies in vitamins A or C or essential fatty acids. [ncbi.nlm.nih.gov]

  Poor adaptation to darkness (nyctalopia) Dry skin Dry hair Pruritus Broken fingernails Keratomalacia Xerophthalmia Corneal perforation Follicular hyperkeratosis (phrynoderma) secondary to blockage of hair follicles with plugs of keratin. [emedicine.medscape.com]

  Malnutrition leads to follicular hyperkeratosis or phrynoderma, manifested by the presence of skin lesions and hyperkeratotic papules. These are often found in shoulders, buttocks and extremities. [symptoma.com]

  Vitamin A deficiency is one of several hypovitaminoses implicated in follicular hyperkeratosis. Night blindness is the difficulty for the eyes to adjust to dim light. [en.wikipedia.org]

• Hyperkeratosis

  Phrynoderma is a rare form of follicular hyperkeratosis associated with deficiencies in vitamins A or C or essential fatty acids. [ncbi.nlm.nih.gov]

  Recently, Ocon Breton et al. 9 described a patient who progressively developed follicular hyperkeratosis located on the extensor surfaces of extremities and xeroftalmia one year after undergoing biliopancreatic diversion. [scielo.isciii.es]

  Poor adaptation to darkness (nyctalopia) Dry skin Dry hair Pruritus Broken fingernails Keratomalacia Xerophthalmia Corneal perforation Follicular hyperkeratosis (phrynoderma) secondary to blockage of hair follicles with plugs of keratin. [emedicine.medscape.com]

  Malnutrition leads to follicular hyperkeratosis or phrynoderma, manifested by the presence of skin lesions and hyperkeratotic papules. These are often found in shoulders, buttocks and extremities. [symptoma.com]

• Skin Lesion

  Deficiency of vitamin A can lead to visual impairment and skin lesions. [britannica.com]

  Characteristic skin lesions are hyperkeratotic papules that first appear on the extensor surfaces of the extremities, shoulders, and buttocks. [ncbi.nlm.nih.gov]

  People deficient in vitamin A may also have dry hair and skin, and brittle nails. Malnutrition leads to follicular hyperkeratosis or phrynoderma, manifested by the presence of skin lesions and hyperkeratotic papules. [symptoma.com]

• Night Blindness

  Her vitamin deficiencies were corrected with appropriate supplements and her night blindness resolved. [ncbi.nlm.nih.gov]

  San Diego: Academic Press, Inc., 1998. vitamin A deficiency A condition characterised by night blindness, keratomalacia, increased urogenital and nasopharyngeal infections, and dry eyes. vitamin A deficiency A condition characterized by night blindness [medical-dictionary.thefreedictionary.com]

  Night Blindness Acute vitamin A deficiency results in night blindness. Vitamin A supplements have helped women to adapt to darkness by 50% within six weeks. Infertility Vitamin A deficiency results in infertility in both men and women. [byjus.com]

• Bitot's Spots

  Key terms Bitot's spots — Bitot's spots are superficial, foamy gray, triangular spots on the white of the eyeball. Carotenoids — Carotenoids are yellow to deep-red pigments. [medical-dictionary.thefreedictionary.com]

  […] were observed in 6.7% of the children with Bitot's spots, bilateral temporal spots in 58.1%, unilateral temporal spots in 25.6%, and 9.4% were not classified. [archive.unu.edu]

  Bitot’s spots at the temporal limbus. Clare Gilbert Figure 2. Bitot’s spots at the temporal limbus. Clare Gilbert Bitot’s spots Bitot’s spots (Figure 2) are characteristic of VAD and are not caused by any other condition. [cehjournal.org]

  Rare – Bitot's spots Bitot's spots (Figure 2 ) are characteristic of VAD and are not caused by any other condition. [ncbi.nlm.nih.gov]

  Bitot's spot is highly suggestive of vitamin A deficiency and, sometimes, chronic conjunctival inflammation. [nejm.org]

• Retinal Pigmentation

  The retinal pigment epithelium and the inner retina appeared intact. Limited and gradual vitamin A supplementation for over a month (20 000 IU/day) led to a dramatic improvement in retinal function and to the resolution of the symptoms. [ncbi.nlm.nih.gov]

  Processes include maintenance of the conjunctival and corneal epithelial surfaces, retinal phototransduction, and retinal pigment epithelial viability. [pharmacytimes.com]

• Lacrimation

  The signs indicating VAD include [1]: Dryness: The lacrimal gland fails to produce tears which causes an insufficent tear film covering the cornea. A poor tear film means pain, poor vision and puts the eye at risk for corneal ulcers and infections. [optometrystudents.com]

• Confusion

  These symptoms can be part of Wernicke’s encephalopathy, which also includes ataxia and confusion. Copper deficiencies affect the optic nerve rarely, but cause optic neuropathy, myelopathy, or myeloneuropathy. [pharmacytimes.com]

  It can lead to mental confusion and forgetfulness because vitamin B-12 is necessary for healthy brain function. Without treatment for vitamin B-12 deficiency, neurological complications can become permanent. [mayoclinic.org]

  When we are inauthentic, a child feels it and becomes very confused. When met with a caregiver who offers an inauthentic response, the child becomes extremely dys-regulated. She will unconsciously either up the ante or shut down emotionally. [coloradoplaytherapy.com]

  Sanam Baloch Morning Show Weight Loss Tips aunt can no longer be confused Gongqing does not move! Sanam Baloch Morning Show Weight Loss Tips Oh! Dong Zhao immediately said yes Good in Guanzhong! [slcrb.by]

• Myelopathy

  B12 and folate deficiencies can produce a type of myelopathy similar to that produced by copper deficiency, and differentiation on the basis of laboratory tests, neurophysiology and improvement of symptoms after replacement therapy might be the hallmark [ncbi.nlm.nih.gov]

  Copper deficiencies affect the optic nerve rarely, but cause optic neuropathy, myelopathy, or myeloneuropathy. All of these symptoms can indicate subacute gait disorder with prominent sensory ataxia and/or spasticity. [pharmacytimes.com]

• Encephalopathy

  Vitamin B1 (thiamine) The clinical features are characteristic of Wernicke encephalopathy seen in chronic alcoholics due to thiamine deficiency. [pgblazer.com]

  These symptoms can be part of Wernicke’s encephalopathy, which also includes ataxia and confusion. Copper deficiencies affect the optic nerve rarely, but cause optic neuropathy, myelopathy, or myeloneuropathy. [pharmacytimes.com]

• Nystagmus

  Vitamin B 1, or thiamine, deficiencies can also impact ophthalmic functions, causing nystagmus and opthalmoplegia. These symptoms can be part of Wernicke’s encephalopathy, which also includes ataxia and confusion. [pharmacytimes.com]

• Asthenia

  A slight amelioration of the patient's generalized weakness, asthenia, increased bowel habit, cutaneous lesions and sensory symptoms was acknowledged, but clinical manifestations reappeared early after she was dismissed. [scielo.isciii.es]

Serum concentration of retinol is an important measure of vitamin A in the body and can be examined using high-performance liquid chromatography. In children below the age of 12 years, serum concentration below 0.7 mg/L is considered to be low and of concern.

RBP can be measured using immunologic assay and is less costly when compared to serum retinol levels. Levels of zinc can affect the serum retinol concentration and hence is included in some laboratory investigations for checking deficiency. Albumin levels are also suggested as it gives an indirect measure of the vitamin in serum.

If anemia is suspected, a complete blood picture is recommended. This will also indicate any kind of infection or sepsis. To understand the nutritional status, liver function test and evaluation of electrolytes are useful. Dark adaptation test is also recommended in some cases [8].

Subclinical forms of vitamin A deficiency may not have many symptoms and can be resolved by taking more of vitamin-rich foods. Eggs, green leafy vegetables, fortified foods, carrots, liver and beef are all good sources of vitamin A. Those who present with clinical VAD are recommended to take oral vitamin A supplements. The recommended dose for adults is 10,000 IU while in children the dosage varies with the age as given below:

• Below 3 years: 2,000 IU
• 4-8 years: 3,000 IU
• 9-13 years: 5,665 IU
• 14-18 years: 9,335 IU

For severe forms of VAD, dose range of 200,000 IU is often suggested. Using oral supplements in children below 5 years reduced the mortality rate by almost 24% [9].

Deficiency of vitamin A can affect many physiological functions in the body and lead to complications. Children of preschool age and pregnant women are at higher risk of developing these conditions. Xerophthalmia, night blindness and anemia are associated with VAD.

When present, vitamin A deficiency may worsen an infection and severe form of VAD may lead to death. In many cases, the condition can be resolved by intake of vitamin A supplements or a well-balanced diet. Providing vitamin A supplements for children below the age of 6 months was found to reduce mortality rate by 21% [7]. Loss of vision due to the deficiency is often permanent. Night blindness improves when the serum concentration of retinol increases. If the deficiency is caused by any of the secondary factors like an underlying disease, the condition can be improved only by treating the disorder. Recurrence is also common in cases where a well-balanced diet is not followed.

Malnutrition is one of the primary causes of vitamin A deficiency. Dietary insufficiency of this vitamin is very common among people who have rice as their staple food. Conditions of protein-energy malnutrition like Marasmus and Kwashiorkor also lead to vitamin A deficiency. When the intake of this vitamin through diet is insufficient, it affects vision and impairs tissue function in general.

Secondary causes like increased requirement of vitamins, defect in intestinal absorption and metabolic changes also result in VAD. The requirement of vitamin A is found to be more in children who are sick leading to a deficiency of this vitamin. VAD is associated with xerophthalmia and measles [2]. Defect in intestinal absorption of fats due to gastrointestinal diseases like inflammatory bowel disease, cystic fibrosis, obstruction in the bile duct or pancreatic insufficiency, will in turn affect the absorption of fat-soluble vitamins. The risk of VAD is increased in people who had duodenal bypass surgery. Other dietary factors like deficiency of zinc and abetalipoproteinemia can affect the absorption of carotenoids and thus lead to VAD.

Vitamin A deficiency is prevalent in most of the developing countries including South East Asia and Africa [2]. Economically deprived population like refugees, immigrants and displaced communities face severe form of vitamin A deficiency [3]. Most of the developing countries have clinical form of the deficiency in which children present with different ocular symptoms including blindness. Malnourished children have an increased risk of developing this deficiency. Most of these children develop xerophthalmia, keratomalacia and other complications. A major part of the population in these countries also show subclinical form of VAD, where in vision in the dark is considerably affected.

As per the recent estimate by WHO, prevalence of VAD (as measured by the presence of night blindness in preschool children) is of moderate to severe public health significance in 122 countries [4]. The report also shows that about a third of the children in the preschool age is vitamin A deficient. An approximate number of 250,000 children become blind because of this nutrient deficiency. Improving the dietary intake of vitamin A or through supplements reduce the risk of complications and mortality [1]. A survey conducted by US Centers for Disease Control and Prevention showed that males had a better intake of the vitamin when compared to females. The level of intake varied considerably among the different ethnic groups in the country [5].

Retinoids and carotenoids are converted into retinyl esters which are absorbed from the intestine and transported to the liver for storage. About 80% of vitamin A in the body is stored in the liver in the form of hepatic retinol binding protein (RBP). The rest is stored in other regions like adipose tissue, lungs and kidneys. When the need arises, these retinyl esters undergo de-esterification and are transported to peripheral tissue region where they are taken up.

The body homeostatically maintains a small retinol concentration in the serum (40-50 mcg/dL). This serum concentration of retinol is indicative of the vitamin A levels in the body. When the store of vitamin A in different regions drops considerably, the serum level also shows a decline. A number of factors affect the measure of retinol in serum including infections, dietary intake of vitamin A, level of nutrients like zinc and iron, and synthesis of RBP in the liver [6].

Deficiency of zinc affects the synthesis of RBP and the impaired protein in turn affects the transportation of retinyl esters from their point of storage to peripheral tissues. Absorption of carotenoids depends on the source. Human body absorbs only about 60% of the plant carotenoids while it is able to absorb about 80-90% of retinyl esters from animal sources. Deficiency of nutrients like zinc and proteins also determine the level of carotenoid absorption. Gastrointestinal diseases and conditions that affect the absorption of fat will ultimately affect the absorption of vitamin A as it is fat-soluble. Diseases like cystic fibrosis, pancreatic insufficiency, and inflammatory bowel disease may all affect the level of serum retinol concentration. Alcohol consumption affects the metabolism of retinol by hindering the conversion of retinol to retinoic acid.

Having a well-balanced diet is the most appropriate preventive measure for VAD. Including 4-5 servings of vegetables and fruits in the diet helps to provide a good supply of carotenoids and other provitamins. Opt for more of fortified foods like cereals, cereal-bars, and crackers to improve the quality of food. Include more animal sources of vitamin A like beef, chicken, egg yolk, whole milk, and liver. Green leafy vegetables, and colored fruits like oranges and mangoes are also good sources of vitamin A that provide sufficient amounts of carotenoids.

Vitamin A deficiency or VAD is a major micronutrient deficiency affecting millions of people worldwide, especially in the developing countries. Vitamin A, one of the first fat-soluble vitamins to be discovered, is essential for many physiological functions including vision, reproduction, growth and maintenance of epithelial layer, immunity, and growth of bones. They also play an important role in embryonic development and regulation of gene expression and differentiation in adults. Deficiency of this vitamin is one of the leading causes of visual impairment in children and is prevalent in more than 75 countries in the world. Vitamin A deficiency increases the chance of mortality and diseases in children. This condition is preventable and implementing timely and appropriate measures can considerably reduce mortality among children [1].

Vitamin A deficiency is caused by insufficient intake of vitamin A in the diet. It results in a number of complications like night blindness, dryness of the eyes, reduced immunity, loss of vision, and if not treated, it may even lead to death. Vitamin A deficiency is more prevalent in developing countries like Africa and South East Asia. It is more common among young children and pregnant women as their requirement for vitamins are more than normal. It is one of the leading cause of blindness in children worldwide.

One of the earliest symptoms of vitamin A deficiency is the difficulty to see in the dark, called night blindness. The eye finds it difficult to adjust the vision when the light is less. Conjunctiva, the transparent covering of white of the eye, may dry in severe cases of this deficiency. When left unattended, it may also lead to development of ulcers in the cornea. This may further result in loss of vision which is permanent.

Doctors may suggest an eye examination and evaluation of medical history to diagnose the condition. Laboratory tests to measure the amount of vitamin A in the serum is also recommended. In many cases, presence of night blindness is used as the most common indicator of this condition.

Mild and moderate forms of vitamin A deficiency is treated by a change in the diet. Including more of vitamin A-rich foods like vegetables and fruits, and vitamin-fortified foods like cereals and bread helps in improving the vitamin level in the body. Severe form of deficiency is treated using oral supplements of vitamin A. The dosage of these supplements depends on the age. In most of the cases the condition can be reversed with appropriate measures like diet and supplements. But if blindness has progressed, it would be difficult to bring it back to normal again. Including up to 5 servings of vegetables and fruits to increase the intake of vitamins and other nutrients helps to prevent this deficiency. 

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2. Reddy V. History of the International Vitamin A Consultative Group 1975-2000. J Nutr. 2002;132(9 ):2852S-2856S.
3. West K, Mehra S. Vitamin A Intake and Status in Populations Facing Economic Stress. Journal of Nutrition. 2009;140(1):201S-207S.
4. World Health Organization. Global Prevalence Of Vitamin A Deficiency In Populations At Risk 1995-2005 WHO Global Database On Vitamin A Deficiency. Geneva: World Health Organization; 2009:3-55.
5. Centers for Disease Control and Prevention. Dietary Intake Of Vitamins, Minerals, And Fiber Of Persons Ages 2 Months And Over In The United States: Third National Health And Nutrition Examination Survey, Phase 1, 1988-91. Maryland: National Center for Health Statistics; 1994.
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