Choline deficiency, symptoms

Folate (foUc acid) is an essential vitamin which, in its active form of tetrahydrofolate (THF, Figure 4-1), transfers 1-carbon groups to intermediates in metaboUsm. Folate plays an important role in DNA synthesis. It is required for the de novo synthesis of purines and for the conversion of deoxyuridine 5-monophosphate (dUMP) to deoxythymidine 5 -monophosphate (dTMP). Additionally, folate derivatives participate in the biosynthesis of choline, serine, glycine, and methionine. However, in situations of folate deficiency, symptoms are not observed from the lack of these products as adequate levels of chohne and amino acids are obtained from the diet. (See also Case 3.)... 

Deficiency symptoms, including slow growth and fatty infiltration of the hver, have been produced in chicks and pigs. Choline is also concerned with the prevention of perosis or slipped tendon in chicks. The choline requirement of animals is imusually large for a vitamin, but in spite of this, deficiency symptoms are not common in farm animals because of its wide distribution and its high concentrations in foods, and because it can be readily derived from methionine. 

DEFICIENCY SYMPTOMS. Many dietary factors seem to contribute to the development of vitamin E deficiency symptoms among them, total fat, unsaturated fats, cod-liver oil (which is high in unsaturated acids), amount of protein, choline, cystine, inositol, cholesterol, vitamin A, and minerals... 

Acid sphingomyelinase is a lysosomal enzyme that catalyzes the breakdown of sphingomyelin to ceramide and phosphoryl-choline.A deficiency of this enzyme leads to lysosomal accumulation of sphingomyelin in patients with Niemann-Pick disease. Recent data indicate that correct intracellular targeting of acid sphingomyelinase to lysosomes is dependent on the mannose 6-phosphate-mediated pathway. Does this imply that the I-cell patient will present with Niemann-Pick symptoms Can I-cell disease be viewed as a constellation of many lysosomal storage diseases ... 

It is believed that the vitamin B12 requirement for choline synthesis contributes to the neurologic symptoms of vitamin B12 deficiency. The methyl groups for choline synthesis are donated by SAM, which is converted to S-adenosylho-mocysteine in the reaction. Recall that formation of SAM through recycling of homocysteine requires both tetrahydrofolate and vitamin B12 (unless extraordinary amounts of methionine are available to bypass the B12-dependent methionine synthase step). 

The minimum manganese requirement of birds for the prevention of any of the above symptoms of deficiency depends upon three principal factors. These are (1) the breed, or even strain, of bird, (2) the quantity of calcium, phosphorus, and iron in the diet, and (3) the source, i.e., the form, of manganese supplied. The incidence of perosis may also be influenced by the level in the diet of several organic nutrients, of which choline and inositoU appear the most important. This aspect of perosis has been well reviewed by Jukes to 1941. 

Experimental pyridoxine deficiency causes dental caries as well as atherosclerosis. Dental caries increase as a result of civilization and availability of refined and preserved food in general (see Scott, 1956). Wartime circumstances reduced dental caries (Toverud, 1956, 1957) as well as death from coronary sclerotic diseases and the incidence of toxemia of pregnancy. Cirrhosis of the liver has been mentioned also as a sequel of pyridoxine deficiency. The role of a deficiency of lipotropic factors such as choline, methionine, inositol, etc., in this respect has been known for a much longer time. Feeding of vitamin Bu can make the symptoms of atherosclerosis much worse (Annand, 1957). Pantothenic acid deficiency results in a lowering of the cholesterol level in man (Bean el al., 1955). 

Thus, the metabolic needs for choline can be supplied in either of two ways by dietary choline as such, or by choline synthesis in the body which makes use of labile methyl groups. But the synthesis in the body cannot take place fast enough to meet the choline needs for rapid growth hence, the symptoms of deficiency may result. 

---