History

Fact Explanation
Night blindness Reduced vitamin A stores in the retina causes reduced rhodopsin production. Rhodopsin is attached to rod cells which are sensitive to light of low intensity. Hence rhodopsin deficiency leads to problems with dark adaptation causing night blindness [1]. Note that this is the earliest clinical feature of Vitamin A deficiency [2].
Dryness and discoloration of the conjunctiva and cornea (conjunctival & corneal xerosis) Vitamin A is involved in glycosylation of glycoproteins including mucin, which is needed for epithelial function of the cornea [3]. Reduced vitamin A causes replacement of mucus secreting epithelium with stratified squamous epithelium leading to absent tears and dry eyes (xerophthalmia) [1].
Silver-gray spots on the conjunctiva (Bitot spots) This is caused by adherence of conjunctival debris on to the dry conjunctiva [4]. It is important to note that night blindness, conjunctival & corneal xerosis and bitot spots are completely reversible changes if the stores are replenished early [2].
Recurrent infections Vitamin A has a role in antibody production against rotavirus, E.coli & cholera toxin [5], and in T cell function [6]. Thus vitamin A deficiency will cause increased incidence if diarrheal infections in children and hence increase mortality with persistent diarrhea [7]. Also, the mucus secreting epithelium in trachea and bronchi are replaced by keratinizing epithelium in vitamin A deficiency, that may cause respiratory infections [2].
References
  1. WEBER, F. Biochemical mechanisms of vitamin A action. Proceedings of the Nutrition Society [Online].Cambridge University Press. January 1983, 42 (1): 31- 41 [viewed 10th April 2014]. Available on: DOI: http://dx.doi.org/10.1079/PNS19830005.
  2. EDEM, D.O. Vitamin A:A Review. Asian Journal of Clinical Nutriton [Online]. Asian Network for Scientific information. 2009, 1 (1):65-82 [viewed10th April 2014]. Available on: doi: 10.3923/ajcn.2009.65.82.
  3. KIM, Yang-Cha Lee. George WOLF. Vitamin A Deficiency and the Glycoproteins of Rat Corneal Epithelium. The Journal of Nutrition [Online]. The American Society of Nutrition. June 1974, 104 (6):710-718 [viewed 10th April 2014].
  4. CACCAMISE, William Charles. Blackened Bitot's spot in Vitamin A deficiency [Online]. The university of IOWA, 2008 [viewed 16 April 2014]. Available from: http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/blackened-bitots-spot-in-vitamin-a-deficiency.html
  5. AHMED, Faruk, David B. JONES, Alan A. JACKSON. Effect of vitamin A deficiency on the immune response to epizootic diarrhoea of infant mice (EDIM) rotavirus infection in mice. British Journal of Nutrition [Online]. Cambridge university press. May 1991, 65 (3): 475 – 485 [viewed 16 April 2014]. Available on: DOI: http://dx.doi.org/10.1079/BJN19910106.
  6. COUTSOUDIS, Anna, Photini KIEPIELA, Hoosen M. COOVADIA, Michael BROUGHTON. Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles. Pediatric infectious disease journal [Online]. Ovid Technologies, Inc. March 1992, 11(3): 203-8 [viewed April 16 2014].
  7. BHANDARI, Nita, Maharaj K. BHAN, Sunil SAZAWAL. Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity. British medical journal [Online]. BMJ Publishing Group Ltd. November 1994, 309:1404 [viewed 16 April 2014]. Available on: doi: http://dx.doi.org/10.1136/bmj.309.6966.1404.

Examination

Fact Explanation
Keratomalacia / corneal ulceration This is usually seen bilaterally in severe vitamin deficiency [1].
Corneal scarring Results from loss of deep corneal tissue from keratomalacia [2]. Important to note that corneal scarring and keratomalacia result in irreversible damage that may lead to blindness [3].
Poor growth Vitamin A causes growth retardation and bone malformation [4]. This may be partly due to recurrent infections caused by vitamin A deficiency, suppressing the growth [5].
Degeneration of reproductive organs Vitamin A is involved on RNA synthesis of testes, and deficiency has shown differences in RNA synthesis from those with normal vitamin A [4]. Also, animal studies have shown reduced follicular stimulating hormone (FSH) secretion and reduced FSH response to gonadotropin releasing hormone (GnRH) [6]. These may be the causes for degeneration of reproductive organs.
Anemia This is thought to be caused by a combination of factors including modulation of erythropoiesis, modulation of immunity to infectious diseases and the anemia of infection, and modulation of iron metabolism caused by vitamin A deficiency [7].
References
  1. GOPALAN, C., P.S. VENKATACHALAM, Belavadi BHAVANI. Studies of vitamin A deficiency in children. American Journal of Clinical Nutrition [Online]. American society for nutrition. November-December 1960, 8:833-40 [viewed 17 April 2014].
  2. SOMMER, Alfred. Vitamin A deficiency and its consequences: A field guide to detection and control[Online]. 3rd ed. England: World Health Organization, 1995 [viewed 17 April 2014]. Available from: http://apps.who.int/iris/bitstream/10665/40535/1/92415447783_eng.pdf.
  3. EDEM, D.O. Vitamin A:A Review. Asian Journal of Clinical Nutriton [Online]. Asian Network for Scientific information. 2009, 1 (1):65-82 [viewed10th April 2014]. Available on: doi: 10.3923/ajcn.2009.65.82.
  4. WEBER, F. Biochemical mechanisms of vitamin A action. Proceedings of the Nutrition Society [Online].Cambridge University Press. January 1983, 42 (1): 31- 41 [viewed 10th April 2014]. Available on: DOI: http://dx.doi.org/10.1079/PNS19830005.
  5. 11. HADI, H ., M.J. DIBLEY, K.P. WEST JR. ORIGINAL COMMUNICATION: Complex interactions with infection and diet may explain seasonal growth responses to vitamin A in preschool aged Indonesian children. European Journal of Clinical Nutrition [Online]. Nature Publishing Group 2004, 58: 990-99 [viewed 11th April 2014]. Available on: doi:10.1038/sj.ejcn.1601920.
  6. HUANG, H.S.F., G. DYRENFURTH, G.L. GUNSALUS, C. HEMBEREE. Effet of vitamin A deficiency upon gonadotropin response to gonadotropin releasing hormone. Biology of reproduction [Online]. Society for the Study of Reproduction. December 1985, 33 (5):1176-87 [viewed 18 April 2014]. Available from: doi: 10.1095/biolreprod33.5.1176.
  7. SEMBA, R.D., M.W. BLOEM. REVIEW: The anemia of vitamin A deficiency: epidemiology and pathogenesis. European Journal of Clinical Nutrition [Online]. Nature Publishing Group 2002, 56: 271–281 [viewed 11th April 2014].

Differential Diagnoses

Fact Explanation
Zinc deficiency Produces night blindness by creating a functional vitamin A deficiency, as zinc is needed to produce retinol binding protein, which is the carrier protein of vitamin A. Hence it gives a clinical picture similar to Vitamin A deficiency [1].
Severe protein malnutrition This also causes a functional vitamin A deficiency by reduced production of the retinol binding protein [1].
Iron deficiency Can cause problems in vision due to the reduced production of heme cofactor which is needed to produce nicotinic acid nucleotides, which are involved in interconversion of vitamin A derivatives during the visual process [1].
Copper deficiency Copper is also involved in the production of nicotinic acid nucleotides which are responsible for vitamin A metabolism, thus may cause problems in vision [1].
References
  1. EDEM, D.O. Vitamin A:A Review. Asian Journal of Clinical Nutriton [Online]. Asian Network for Scientific information. 2009, 1 (1):65-82 [viewed10th April 2014]. Available on: doi: 10.3923/ajcn.2009.65.82.

Investigations - for Diagnosis

Fact Explanation
Serum retinol concentration This is a commonly used test to look for vitamin A status. Disadvantages of this test is that it needs expensive laboratory equipment, and retinol is unstable to heat and light [1].
Retinol binding protein (RBP) test This is a simple and inexpensive test to look for vitamin A deficiency. The level can be reduced in acute phase response and protein malnutrition despite normal vitamin A level, giving a false result [2].
Relative dose–response (RDR) test This test is based on the principle that there is a relative excess of RBP in the liver in vitamin A deficiency, which is released into the circulation after a test dose of vitamin A. Disadvantages of this test is that 2 blood samples need to be withdrawn and the children should be observed for 5 hours [3].
Serum 30 day dose response test This is similar to RDR test except that the second blood sample is collected 30-45 days after a vitamin A dose of 200,000 IU, and serum retinol concentration is measured instead of RBP [3].
References
  1. World Health Organization. Indicators for assessing vitamin A deficiency and their application in monitoring and evaluating intervention programs. Geneva: World Health Organization, 1996. Available from.
  2. BAETEN, Jared M., Barbra A. RICHARDSON, Daniel D. BANKSON, Mark H. WENER et al. Use of serum retinol-binding protein for prediction of vitamin A deficiency: effects of HIV-1 infection, protein malnutrition, and the acute phase response. American Journal of Clinical Nutrition [Online] American Society for Clinical Nutrition. 2004, 79:218 –25[viewed 13th April 2014].
  3. FERRAZ, I.S., J.C. DANELUZZI, H. VANNUCCHI, A.A. JORDA˜O JR et al. Detection of vitamin A deficiency in Brazilian preschool children using the serum 30-day dose–response test. European Journal of Clinical Nutrition [Online]. Nature Publishing Group. March 2004, 58:1372–1377 [viewed 18 April 2014]. Available from: doi:10.1038/sj.ejcn.1601978.

Investigations - Followup

Fact Explanation
Investigations to asses serum vitamin A level Serum RBP/ serum retinol concentration can be carried out to asses vitamin A level in serum.
Ocular investigations (slit lamp examination/ ophthalmoscopy) These should be carried out by an ophthalmologist to asses the response to treatment and follow-up of eye complications of vitamin A deficiency [1].
References
  1. SOMMER, Alfred. Vitamin A deficiency and its consequences: A field guide to detection and control[Online]. 3rd ed. England: World Health Organization, 1995 [viewed 17 April 2014]. Available from: < http://apps.who.int/iris/bitstream/10665/40535/1/92415447783_eng.pdf>.

Management - General Measures

Fact Explanation
Increase the intake of dietary vitamin A by promotion of breast feeding and health education on natural sources of vitamin A. Establishment of early breast feeding: This helps to prevent vitamin A deficiency in infancy [1]. Also administration of vitamin A oral mega dose to the mother after the delivery increases the vitamin A concentration in breast milk. Animal & plant sources: Vitamin A is mainly available in animal products such as meat, liver, milk, egg yolk, butter, cod liver oil & animal fat. Plant products that are rich in vitamin A are orange & yellow vegetables, leafy green vegetables and yellow corn [2].
References
  1. Micronutrient deficiencies: vitamin A deficiency. World Health Organization, 2014 [viewed 18 April 2014]. Available from : http://www.who.int/nutrition/topics/vad/en/.
  2. EDEM, D.O. Vitamin A:A Review. Asian Journal of Clinical Nutriton [Online]. Asian Network for Scientific information. 2009, 1 (1):65-82 [viewed10th April 2014]. Available on: doi: 10.3923/ajcn.2009.65.82.

Management - Specific Treatments

Fact Explanation
Periodic supplementation of vitamin A Vitamin A oral dose is administered every 6 months with the vaccination program in developing countries. This is proven to reduce mortality among children [1]. Additionally, vitamin A should be given to all the children with life threatening measles and all the children with measles under 2 years, as measles is considered to deplete vitamin A stores. Also children with severe protein-energy malnutrition, chronic diarrhea, recurrent respiratory infections and those who are coming with vitamin A deficient communities should receive vitamin A therapy [2].
Food fortification This is a better management option for high risk populations. Eg: fortification with sugar in Guatemala [1].
Management of eye complications Xerophthalmia: this is a medical emergency with high risk of blindness, sepsis or death. Prompt treatment with vitamin A mega dose(200,000 IU), management of co-existing illnesess, and correction of protein-energy malnutrition should be undertaken. Also, a broad spectrum antibiotic eye ointment should be applied to prevent secondary infection [2].
References
  1. Micronutrient deficiencies: vitamin A deficiency. World Health Organization, 2014 [viewed 18 April 2014]. Available from: http://www.who.int/nutrition/topics/vad/en/.
  2. SOMMER, Alfred. Vitamin A deficiency and its consequences: A field guide to detection and control[Online]. 3rd ed. England: World Health Organization, 1995 [viewed 17 April 2014]. Available from: http://apps.who.int/iris/bitstream/10665/40535/1/92415447783_eng.pdf.