Correlation of serum vitamin A and its transport protein (RBP) in malnourished and vitamin A deficient children.

MK Jain, NJ Mehta, M Fonseca, NV Pai 
 Dept. of Paediatrics, K. E. M. Hospital, Parel, Bombay, Maharashtra.

Correspondence Address:
M K Jain
Dept. of Paediatrics, K. E. M. Hospital, Parel, Bombay, Maharashtra.

Full Text

::   Introduction

The industrial production of vitamin A in large quantity made it possible to maintain the child free of signs of vitamin A deficiency at a very marginal cost. Yet, there are about 9-10 million blind children due to vitamin A deficiency. The National Institute of Nutrition at Hyderabad study showed an almost 5 to 10% of children belonging to poor income group suffered from vitamin A deficiency. The ICMR study in 1973-75 revealed that 2% of the 9 million blind were caused by keratomalasia[3]. The Ministry of Health, Govt. of India 1986 statistics showed about 40,000 children turned blind every year mainly due to vitamin A deficiency[2]. There is high prevalence of vitamin A deficiency in preschool and school children of economically poorer section of population[15].

The present study is undertaken to study the vitamin A metabolism in malnourished and vitamin A deficient children and also its effective route of administration to prevent its deficiency.

::   Material and method

Eighty-nine children aged between 1-10 years were studied. Clinical signs of vitamin A deficiency were classified according to WHO nomenclature.14 Nutrition status of these children was assessed as per Wellcome classification [1]. They were grouped as normal (81-100%), underweight (61-80%), and protein energy malnutrition (PEM) weighing less than 60% of the reference (ICMR) weight standard. All the cases of marasmus and marasmic kwashiorkor were grouped as PEM. All these children were clinically examined for the presence of any associated illness.

Blood samples were collected after 4-6 hours of fasting from all the children initially. For absorption study, some of them were given water miscible vitamin A palmitate (aquasol) 100,000 I. U. orally or intramuscularly. The repeat blood was collected after 48 hours of vitamin A administration.

All the blood samples were analysed for Retinol, retinol-binding-protein (RBP), total protein and albumin. Retinol (vitamin A alcohol) was determined by flourimetry as described by Hansen et al [4]. Serum RBP was assayed by radial immunodiffusion technique as described by Mancini et al[7]. The standard human serum and human anti-RBP serum was obtained from Behringwerke, West Germany.

::   Results

There were 37 control children, of them 12 were undernourished but had no signs of PEM or vitamin A deficiency. Twenty-seven children had signs of vitamin A deficiency of which, nine had normal weight and eighteen were underweight. There were 25 children with protein energy malnutrition of which 15 malnourished children (PEM) exhibited signs of vitamin A deficiency. Xerosis (X-A) was present in 23 cases, 14 had Bitot's spot (X1B); and 5 had corneal ulceration and keratomalasia. (X2 and X3). There were 13 children with marasmic kwashiorkor and 12 marasmic.

Vitamin A deficiency was associated with lower levels of serum protein, albumin, retinol and retinol-binding-protein (RBP) even in normal and underweight children. PEM also had significant lower levels of retinol and RBP along with hypoproteinemia but their levels do not differ significantly from that of vitamin A deficient children. [Table:1]. Aqueous vitamin A (100,000 I.U) was given orally and parenterally to 18 and 17 children respectively. There was rise in serum retinol and RBP levels in vitamin A deficient as well PEM patients after 48 hours of administration of vitamin A, but the levels were significantly higher (p < 0.001) after oral administration [Table:2]. Higher levels of retinol were achieved in PEM cases by oral route.

::   Discussion

The prevalence of vitamin A deficiency is about 5 to 10% of children of economically poorer section of the population[14]. A School survey in Calcutta revealed that 5% of the children were found to be suffering from xeropthalmia and its after effects[11]. Though dietary deficiency of vitamin A appears to be associated with clinical syndrome of hypovitaminosis A, protein deficiency is also equally important as it leads to deficiency of carrier protein i.e. retinol-binding-protein (RBP). Under normal circumstances RBP is bound to pre-albumin (PA) forming PA-RBP complex. This complex strengthens and stabilizes the interaction between RBP and retinol (vitamin A alcohol)[5].

Serum levels of retinol, RBP and serum protein and albumin were low in children with signs of vitamin A deficiency irrespective of their nutrition status. PEM had lower levels too, but the difference between PEM and vitamin A deficient group was not statistically significant.

Normal and underweight children with signs of vitamin deficiency had also statistically significant low levels of these parameters.

A slow rise in serum retinol and RBP levels was observed by Smith et al[12],[13], when children with kwashiorkor were treated with high protein and caloric diet without the administration of vitamin A. In the present study, a significant rise was observed within 48 hours in the concentration of serum retinol and RBP levels after the oral or parentaral administration of vitamin A, in children with PEM as well was with vitamin A deficiency. These observations are in line with those reported in rats[8],[9],[10] and suggest that PEM interferes with hepatic synthesis of RBP and the release of RBP from the liver depends on the availability of vitamin A. Thus vitamin A is a limiting factor, the presence of which is requited for the release of apo-RBP from the liver. The serum retinol transport system is also influenced by the body's nutritional vitamin A status; when the hepatic stores of vitamin A are low in children with PEM, the institution of aminoacid substrates and calories fail to produce rise in serum concentration. Furthermore, vitamin A supplementation without change in either protein or caloric intake in children with PEM can produce an increase in the serum concentration of both retinol and RBP[12].

Decrease serum retinol levels and clinical vitamin A deficiency have been observed in children with PEM. Serum retinol transport might be defective in this clinical syndrome. Kanai et al[6] also suggested this by studying the role of RBP and pre-albumin. Ingenbleek et al[5] suggested that correlation persists between RBP and retinol plasma level along the 7 successive steps of clinical recovery suggesting that RBP acts as a limiting factor for retinol transport.

Retinol transport system was examined in children with PEM and vitamin A deficient children in this study by giving them oral and parenteral dose of vitamin A. Though we have not measured the percentage of dose absorbed after the administration of oral vitamin A, we have found almost two fold rise in serum retinol and RBP level, rise in serum retinol being slightly better in PEM cases.

In PEM, the availability of vitamin A is decreased as a result of poor dietary intake; which in turn decreases hepatic synthesis of RBP. The administration of vitamin A not only stimulates the release of apo-RBP but also the hepatic synthesis of RBP. These children should therefore be treated with vitamin A in addition to dietary protein and calories. Vitamin A deficiency can be treated, by giving massive dose of vitamin A, as it is absorbed fairly well even in PEM though absorption may be slightly diminished when PEM is associated with diarrhoea.

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