Vitamins - sepeap

Article nutrition 

Vitamins 

Usha Sethuraman, MD* 

Author Disclosure 

Dr Sethuraman did 

not disclose any 

financial relationships 

relevant to this 

article. 

Objectives After completing this article, readers should be able to: 

1. Identify the symptoms and signs of deficiency of various vitamins. 

2. Characterize the patients at risk for deficiencies and plan their treatment. 

3. Discuss the treatment of patients at risk for vitamin deficiencies. 

Introduction 

Vitamins are organic compounds required in small amounts in various cellular metabolisms 

that are important for overall health maintenance and normal growth of the organism. First 

discovered by Hopkins in 1907, they were named by Funk in 1911. McCollum and Davis 

later showed that some vitamins, such as A, D, E, and K, are fat-soluble, and some, such as 

B and C, are water-soluble (Table 1). 

Vitamin A (Retinol) 

Case 1 

A 5-year-old boy who recently was adopted from India is brought by his parents for his first 

physical examination. They report that he has been doing well except that he seems to bump into 

objects frequently, particularly in the evenings. On examination, his height and weight are 

below the 5th percentile. He has some silver-colored patches in his conjunctiva, but the rest of the 

examination findings are normal. A diagnosis is made clinically and treatment initiated. 

Case 2 

A 3-year-old girl is brought to the emergency department for irritability. Her mother denies 

fever, upper respiratory tract infection symptoms, or trauma, but states that the girl has become 

progressively irritable over the past few days. She had been complaining of headache and 

nausea but had no emesis. On examination, the child is afebrile and appears irritable. Despite 

adequate doses of acetaminophen, she continues to complain of a headache, prompting the 

decision to perform a lumbar puncture. Except for an elevated opening pressure, her spinal 

fluid appears normal, having no white or red blood cells. Further questioning reveals that the 

girl has been taking her brother’s pills three to four times a day to “get healthier”; this leads to 

her diagnosis. 

Vitamin Function 

Vitamin A, derived from pigments in nature called carotenoids (provitamin A), is waterinsoluble 

and is destroyed by heat, light, oxidation, and dehydration. Carotenoids and 

retinal in the diet are absorbed and subsequently esterified in the intestinal cells to retinyl 

esters. The esters are stored in the liver and, when needed, hydrolyzed to retinol, 

complexed with retinal-binding protein, and transported to tissues and organs in the body. 

Retinol is essential for growth and functional integrity of epithelial cells; retinal, a 

component of retinal pigments, is important for normal vision. Retinoic acid is essential for 

the synthesis of glycoproteins. 

Vitamin A deficiency is the leading cause of preventable blindness in children; it also 

increases the risk for severe infections. Malnourished young children and infants in 

developing countries are particularly prone to deficiency due to recurrent infections such as 

diarrhea and measles. Vitamin A deficiency also can occur due to inadequate absorption, as 

seen in celiac disease, hepatic disease, and low-fat and -protein diets. 

*Division of Emergency Medicine, Carman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Wayne 

State University, Detroit, Mich. 

44 Pediatrics in Review Vol.27 No.2 February 2006

Pediatrics in Review Vol.27 No.2 February 2006 45 

Table 1. Vitamins: Sources, Requirements, Action, Results, Diagnosis, and Treatment 

Vitamin 

A 

B 1 (Thiamine) 

Riboflavin (B 2 ) 

Niacin 

(Nicotinic 

acid) 

Sources 

Green leafy 

vegetables, 

carrots, sweet 

potatoes, liver 

Liver, pork, milk, 

grains 

Milk, cheese, 

liver, green 

leafy 

vegetables 

Liver, fish, 

whole grains, 

eggs, milk, 

poultry 

B 12(Cobalamine) Fish, eggs, 

cheese 

Daily 

Requirement Action Deficiency Excess Diagnosis Treatment 

14 yr: 1.3 mg 

13 y: 16 mg 

0 to 6 mo: 0.4 mcg 

6 to 12 mo: 0.5 mcg 

1to3y:0.9mcg 

4to8y:1.2mcg 

9to13y:1.8mcg 

>13 y: 2.4 mcg 

Vision in dim light, 

bone and tooth 

growth, 

epithelium 

maturation 

Part of thiamine 

pyrophosphate, 

which is needed 

for oxidative 

decarboxylation 

Part of 

flavoproteins 

important for 

hydrogen 

transfer 

Forms NAD and 

NADP cofactors 

Maturation of red 

blood cells 

Nyctalopia, 

photophobia, 

keratomalacia, 

blindness, 

impaired 

growth, 

follicular 

hyperkeratosis 

Beriberi, fatigue, 

cardiac failure, 

polyneuritis 

Blurring of vision, 

cheilosis 

Pellagra (rash, 

diarrhea, 

stomatitis, 

glossitis, 

mental status 

changes) 

Juvenile 

pernicious 

anemia 

Anorexia, dry skin, 

painful joints, 

increased 

intracranial 

pressure, headache, 

vomiting 

None 

None 

None 

None 

Clinical or low 

plasma retinol 

levels 

Response to 

thiamine 

Urinary riboflavin 

of

46 Pediatrics in Review Vol.27 No.2 February 2006 

Table 1. Vitamins: Sources, Requirements, Action, Results, Diagnosis, and Treatment (continued) 

Vitamin Sources 

B 6 (Pyridoxine) Meat, liver, 

kidneys 

Folate 

Vitamin D 

Vitamin E 

(Tocopherol) 

Cauliflower, 

green leafy 

vegetables, 

yeast, liver, 

kidney 

Fortified milk, 

liver oils, 

sunlight, egg 

yolks 

Germ oils, green 

leafy 

vegetables 

Daily 


13 y: 1.3 mg 

13 y: 100 mcg 

Pediatrics in Review Vol.27 No.2 February 2006 47 

Table 1. Vitamins: Sources, Requirements, Action, Results, Diagnosis, and Treatment (continued) 

Vitamin 

Vitamin K 

Sources 

Green leafy 

vegetables, 

liver 

Daily 


nutrition 

vitamins 

blindness), indicative of vitamin A deficiency. The presence 

of Bitot spots in the eyes confirms the diagnosis. 

The boy was started on vitamin A, and his symptoms 

improved. Delay in diagnosis and treatment would have 

led to blindness. 

Treatment and Prevention 

Breastfeeding is protective against vitamin A deficiency. 

Encouraging vitamin A-rich diets, vitamin A supplementation, 

and food fortification can prevent and treat this 

deficiency. 

Figure 1. Bitot spots. Reproduced with permission from Indiana 

University School of Optometry; pictures by Dr H.D. Riley 

Clinical Manifestations of Deficiency 

The skin of the extensor surfaces becomes dry and scaly 

(follicular hyperkeratosis). Keratinization of the conjunctiva 

and lacrimal glands leads to dryness of the eyes and 

follicular conjunctivitis (xerophthalmia). Bitot spots are 

small triangular, silvery, foamlike patches that appear on 

the conjunctiva due to keratinization (Figs. 1 and 2). 

Night blindness or nyctalopia occurs due to a delay in 

resynthesis of rhodopsin. Severe inflammation results in 

keratomalacia and blindness. Diagnosis is primarily clinical. 

The child in Case 1 was adopted from a developing 

country, where malnutrition and vitamin deficiencies are 

more common. His height and weight are less than the 

5th percentile. The history of bumping into objects in 

the evenings is highly suggestive of “nyctalopia” (night 

Figure 2. Bitot spots. Reproduced with permission from Indiana 

University School of Optometry; pictures by Dr H.D. Riley, 

Effects of Excess 

The child in Case 2 had been taking her brother’s vitamin 

A capsules because her mother thought they would make 

the girl stronger. Drowsiness, painful joints, loss of hair, 

increased intracranial pressure, and carotenemia are presenting 

symptoms of excessive ingestion of vitamin A. 

Vitamin D 

Case 3 

A 2-year-old African-American boy is brought to the pediatrician 

for a routine visit. He was born at 30 weeks’ 

gestation, was exclusively breastfed until 1 year of age, and 

has been a poor feeder since then. His height and weight are 

less than the 5th percentile. His legs are slightly bowed, and 

he has frontal bossing. He has no teeth and is not yet 

walking. Laboratory tests reveal decreased phosphorus, decreased 

calcium, and elevated alkaline phosphatase concentrations. 

Radiography of his wrists documents osteopenia, 

with cupping and fraying of the metaphysis. He is diagnosed 

as having nutritional rickets and is started on calcium 

and vitamin D. His mother is upset and wants to 

know the cause. 

Case 4 

An 8-month-old Caucasian boy is brought to the emergency 

department because of complaints of cough, runny nose, 

and wheezing for the past 3 days. His mother states that he 

has been fussy and has had some redness of his eyes without 

discharge. He is breastfed exclusively. His birthweight was 

3.2 kg, he was delivered vaginally without complications, 

and he has had regular visits with the pediatrician. The 

mother reports that the boy has had multiple episodes of 

bronchiolitis in the past. On physical examination, the baby 

is alert but fussy and has poor muscle tone. He weighs 4.1 kg, 

his heart rate is 160 beats/min, his respiratory rate is 

approximately 80 breaths/min, and his blood pressure is 

normal. His deep tendon reflexes seem to be slightly depressed. 

Bronchiolitis with conjunctivitis and failure to 

thrive is diagnosed, and the child is admitted to the hospital 


nutrition 

vitamins 

on bronchodilators. A chest radiograph reveals a heart of 

normal size and multiple areas of atelectasis. Because of a 

strong family history of asthma, steroids are added to the 

treatment regimen. The laboratory evaluation for the cause 

of the failure to thrive reveals anemia, mild indirect hyperbilirubinemia, 

a lowered calcium level, and an elevated 

alkaline phosphatase level. The radiologist notifies the resident 

of what appears to be cupping and fraying of the 

humerus ends. Additional tests are performed, the diagnosis 

made, and appropriate therapy started. 


Vitamin D exists as ergosterol in yeast and 

7-dehydrocholesterol in human skin. When irradiated 

with ultraviolet light, these are converted into ergocalciferol 

(vitamin D 2 ) and cholecalciferol (vitamin D 3 ), respectively. 

D 2 and D 3 are absorbed readily from the small 

intestines. In the liver, D 3 is hydroxylated by 25 hydroxylase 

to 25 hydroxyl-D 3 (calciferol). Further hydroxylation 

of calciferol by 1-hydroxylase in the kidneys results 

in the formation of 1,25 dihydroxy-D 3 , which is the 

physiologically active form that regulates calcium and 

phosphate metabolisms by releasing calcium from the 

bones into blood and increasing calcium reabsorption in 

the kidney. 

Hypocalcemia causes parathormone to stimulate the 

formation of 1,25 dihydroxy-D 3 , while hypophosphatemia 

stimulates its formation directly; 1,25 

dihydroxy-D 3 , in turn, increases absorption of phosphate 

from the intestines. Vitamin D also increases absorption 

of calcium and phosphorus from the distal ileum and 

promotes endochondral growth of long bones and mineralization 

of the zone of provisional calcification (antirachitic 

action of vitamin D). Hence, deficiency is characterized 

by a defect in mineralization in these areas but 

with continued cartilage growth. Exposure to sunlight 

produces adequate amounts of vitamin D in the skin. 

Rickets can occur in breastfed infants who are not supplemented 

with vitamin D and have inadequate exposure 

to sunlight; in dark-skinned children due to inadequate 

penetration of sunlight; and in children who grow rapidly, 

such as very low-birthweight infants and adolescents. 

Congenital rickets can occur when the maternal 

intake of vitamin D is low. Celiac disease, steatorrhea, 

pancreatitis, cystic fibrosis, and medications such as steroids 

and anticonvulsants can predispose to vitamin D 

deficiency due to malabsorption from the gut. 

Clinical Manifestations of Deficiency 

Infants present with seizures and tetany due to the hypocalcemia, 

hypotonia, failure to thrive, widened cranial 

Figure 3. Widened wrists associated with rickets. Reproduced 

with permission from Dr Tom Thacher, Jos University Teaching 

Hospital, Nigeria. 

sutures, frontal bossing, and craniotabes. Older children 

may show delayed milestones, potbelly, bowlegs, kyphosis, 

pelvic deformities, delayed dentition, and widened 

wrists (Fig. 3). Rachitic rosary due to enlarged costochondral 

junctions may be present (Fig. 4). Harrison 

groove is a horizontal depression along the lower border 

of the chest, corresponding to the costal insertion of the 

diaphragm. This results from ongoing cartilage growth 

and defective bone growth. Deficiency in adults results in 

osteomalacia. 

Diagnosis 

Besides the findings listed in Table 2, a generalized 

aminoaciduria can occur. Radiographs of the knees, 

Figure 4. Rachitic rosary. Courtesy of Dr Tom Thacher, Jos 

University Teaching Hospital, Nigeria. 

Pediatrics in Review Vol.27 No.2 February 2006 49

nutrition 

vitamins 

Table 2. Types of Rickets and Biochemical Findings 

Type 

Vitamin D-deficient 

Vitamin D-dependent 

(type 1) 

Vitamin D-dependent 

(type 2) 

Vitamin D-resistant 

(X-linked 

hypophosphatemia) 

Renal disease 

Cause 

Serum 

Calcium 

Serum 

Phosphate 

Alkaline 

Phosphate 

Parathyroid 

Hormone 

1,25 dihydroxy- 

D 3 

Nutrition/poor 

ultraviolet 

exposure 

Decreased Decreased Increased Increased Normal/decreased 

Decreased 1-alpha Decreased Decreased Increased Increased Low 

hydroxylase 

End-organ resistance Decreased Decreased Increased Increased High 

dihydroxy-D 3 

to 1,25 

Defect in tubular Normal Low Increased Normal Normal/decreased 

reabsorption of 

phosphate 

Defect in phosphate 

excretion 

Mildly 

decreased 

High Increased Increased Decreased 

wrists, and shoulders show widened distal ends with 

cupping and fraying, uncalcified larger metaphyses, and 

osteopenia (Figs. 5 through 7). A line of preparatory 

calcification that is separated from the distal end of the 

shaft by a zone of decreased calcification suggests initial 

healing. 

Nutritional rickets should be distinguished from vitamin 

D-resistant rickets (familial hypophosphatemia), 

which is due to a defect in the proximal tubular reabsorption 

of phosphates and in the conversion of 25 

dihydroxy-D 3 to 1,25 dihydroxy-D 3 . It has an X-linked 

dominant inheritance. Clinically, legs are bowed, but the 

other features of nutritional rickets generally are absent. 

Laboratory findings reveal near-normal calcium levels, 

lower phosphate concentrations, elevated alkaline phosphatase 

values, large urinary phosphate losses, and little 

or no evidence of secondary hyperparathyroidism. Vitamin 

D-dependent rickets is due to reduced activity of 

1-alpha hydroxylase. Levels of calcium and phosphate are 

decreased, alkaline phosphatase concentrations are elevated, 

and the levels of 1,25 dihydroxy-D 3 are low. Renal 

rickets due to the phosphaturia of uremia and secondary 

hyperparathyroidism result from renal disease. 

Figure 5. Radiographic appearance of rickets in the wrist. 

Courtesy of Dr Earl Hartwig, Emergency Medicine, Children’s 

Hospital of Michigan. 

Figure 6. Radiographic appearance of rickets in the knees. 




nutrition 

vitamins 

Figure 7. Radiographic appearance of rickets in the shoulders. 




All infants, including those who are exclusively breastfed, 

should receive a minimum daily intake of 200 IU of 

vitamin D beginning during the first 2 postnatal months. 

Formula-fed infants who ingest less than 500 mL/d of 

formula or milk also should be supplemented. Studies 

have shown a higher bone density in adult women who 

were supplemented with vitamin D in infancy. Once 

deficiency is diagnosed, treatment must be initiated immediately. 

Calcium and phosphorus levels must be corrected. 

Daily oral vitamin D 3 , as listed in Table 1, should 

be initiated. An alternate therapy to ensure compliance is 

15,000 mcg of vitamin D in a single day, which avoids 

the preparation that has ethylene glycol as the vehicle, 

which could be toxic. Nutritional rickets responds with 

an increase in phosphate in 4 days and radiologic evidence 

of healing in 1 to 2 weeks. After healing is complete, 

the dose should be lowered to 10 mcg/d. Vitamin 

D-resistant rickets and -dependent types are treated with 

oral phosphates and high doses of 1,25 dihydroxy-D 3 . 

The prognosis generally is good for rickets. Early 

diagnosis prevents developmental delay and other sequelae. 

Orthopedic intervention may be required for 

severe deformities. 

The child in Case 3 had several factors putting him at 

risk for developing rickets, including his race, preterm 

birth, and exclusive breastfeeding with no supplementation 

until 1 year of age. Recognition of these risk factors 

and early supplementation with vitamin D-containing 

vitamins could have prevented the onset of rickets. Treatment 

now should include correction of calcium and 

phosphorus levels and administration of 50 to 150 mcg 

of vitamin D 3 daily for 2 to 3 months followed by a 

maintenance dose of 400 IU/d. Calcium and phosphorus 

levels and radiographs should be monitored for evidence 

of healing. 

The child in Case 4 had recurrent episodes of wheezing 

with failure to thrive and features of rickets. A sweat 

test performed as part of the evaluation for the failure to 

thrive led to the diagnosis of cystic fibrosis. The resulting 

malabsorption, coupled with the exclusive breastfeeding 

with no supplementation, caused his deficiency in vitamin 

D, leading to his rickets. Due to his reduced deep 

tendon reflexes, additional laboratory tests were undertaken, 

which revealed low levels of alpha-tocopherol and 

retinol. Cystic fibrosis with malabsorption and fatsoluble 

vitamin deficiencies was diagnosed and appropriate 

treatment initiated. The redness of his eyes was due to 

a follicular conjunctivitis caused by vitamin A deficiency 

and resolved when therapy was begun. Repeated episodes 

of “bronchiolitis” and failure to thrive should 

arouse the suspicion for cystic fibrosis, and a high degree 

of suspicion for vitamin deficiencies should be maintained. 


Hypotonia, anorexia, polydipsia, polyuria, dehydration, 

hypertension, and corneal clouding may result from excess 

vitamin D intake. Radiographs may show internal 

calcifications, such as kidney stones and osteoporosis. 

Vitamin E 


Vitamin E includes a group of compounds called tocopherols 

that have antioxidation properties (particularly of 

fats), which are facilitated by the presence of ascorbic 

acid. This vitamin occurs abundantly in green plants such 

as lettuce, vegetable oils, milk, and eggs. Vitamin E helps 

prevent atherosclerosis by inhibiting oxidation of lowdensity 

lipoprotein cholesterol, acts on immunomodulation, 

and appears to inhibit platelet activity. The antioxidant 

properties of vitamin E are believed to protect easily 

oxidizable substances such as polyunsaturated fatty acids 

and sulfhydryl groups against ongoing cumulative effects 

of oxygen free radicals. The result is protection from 

cellular membrane damage throughout the body. Patients 

who have malabsorption, abetalipoproteinemia, 

short bowel syndrome, or cholestatic liver disease and 

very low-birthweight infants can become deficient. Deficiency 

causes muscle weakness, double vision, loss of 


nutrition 

vitamins 

position sense, hemolytic anemia, reduced reflexes, and 

constricted visual fields. 


Inclusion of 0.7 mg/g of unsaturated fat in the diet 

appears to be adequate to treat deficiencies. Special vitamin 

E supplements (eg, tocopherol polyethylene glycol 

succinate) are necessary in children who have malabsorption. 


Nausea, diarrhea, and vitamin K antagonism can be seen 

with excess vitamin E. 

Vitamin K 

Case 5 

An 8-day-old infant presents to a rural emergency department 

with his mother, who today noticed bleeding from his 

umbilical cord and nares. The child was born at home and 

delivered by a midwife. The mother had received no antenatal 

care, and this is the first time the child is being seen by 

a doctor. The history revealed significant bleeding with 

clots. On examination, the child exhibits slight tachycardia 

but has a normal respiratory rate and blood pressure. He 

has constant bleeding from the umbilical cord area and his 

nares. He has no other rashes, and the rest of his physical 

examination findings are normal. Laboratory evaluation 

reveals a prolonged prothrombin and partial thromboplastin 

time, with a normal platelet count. A diagnosis is made 

and treatment given. 


Vitamin K in the diet, along with that formed by intestinal 

bacteria, is absorbed in the jejunum and either used 

rapidly or metabolized. Table 1 lists some of the sources. 

Vitamin K is essential for synthesizing prothrombin. 

Coagulation factors II, VII, IX, and X are vitamin 

K-dependent and are made in the liver. The intestinal 

flora produces adequate amounts. Newborns are vitamin 

K-deficient because of insufficient intestinal bacterial 

flora and may present with uncontrollable bleeding. This 

can be exaggerated in preterm infants, who can present 

with spontaneous and prolonged bleeding between the 

second and seventh postnatal days. Hemorrhage is more 

common in breastfed infants because human milk contains 

relatively little vitamin K. Maternal treatment with 

drugs such as phenytoin can cause early bleeding in 

infants (24 h). Chronic oral antibiotics, biliary obstruction, 

chronic diarrhea, cystic fibrosis, sprue, and hepatic 

damage also can cause deficiency due to malabsorption. 

Bleeding tends to be gastrointestinal, nasal, or intracranial 

or from the circumcision site. Late bleeding has 

been reported up to a few weeks later. Besides the 

laboratory findings listed in Table 1, abnormal bleeding 

occurs with a normal platelet count, bleeding time, and 

plasma fibrinogen levels. 


All newborns should receive 1 mg of vitamin K to prevent 

early vitamin K deficiency; the current recommendation 

is to give all newborns parenteral vitamin K to prevent 

late vitamin K deficiency bleeding. The baby in Case 5 

was delivered at home and received little antenatal or 

perinatal care. The child probably did not receive vitamin 

K, which generally is administered postnatally. This explains 

the bleeding that occurred around the seventh 

postnatal day, the common presentation of this deficiency. 

The elevated prothrombin and partial thromboplastin 

times with normal platelet counts confirm the 

diagnosis. The child was given 2Uofvitamin K, following 

which the bleeding resolved. 


An excess of vitamin K can cause hyperbilirubinemia and 

hemolytic anemia in infants. 

Vitamin B Complex 

These vitamins serve as important coenzymes for important 

intracellular enzymes. A few are discussed. 

Thiamine (Vitamin B 1 ) 

Vitamin B 1 is water-soluble and lost during cooking; 

synthesis is limited in human beings. Human milk, cow 

milk, vegetables, eggs, meat, legumes, and rice polishings 

are good sources. The vitamin is lost from rice 

during the dehusking process. The age-dependent daily 

requirements are listed in Table 1. 

Vitamin B 1 functions as a coenzyme in decarboxylation 

and transketolation of alpha ketoacids and is required 

for the synthesis of acetylcholine; deficiency results 

in beriberi. Irritability, fatigue, peripheral neuritis, 

decreased tendon reflexes, loss of vibration sense, congestive 

heart failure, hoarseness, and ataxia also can occur. 

Edema is present in wet beriberi but absent in dry 

beriberi. Wernicke encephalopathy is characterized by 

mental and eye changes, ataxia, and hemorrhage in the 

brain. 

Once diagnosed, it is important to treat both mother 

and breastfed infant who have beriberi. The daily dose is 

10 mg thiamine for an infant and 50 mg thiamine for an 

adult. 


nutrition 

vitamins 

Riboflavin 

This vitamin is important in hydrogen transfer reactions, 

for the normal metabolism of tryptophan, and for retinal 

pigment. Deficiency results in cheilosis, glossitis, keratitis, 

photophobia, seborrheic dermatitis, and anemia. 

Oral riboflavin should be given at a dose of 3 to 10 mg 

daily. 

Niacin 

Niacin forms NAD and NADPH, both important enzymes 

in electron transport and glycolysis. It also is the 

end product of the metabolic pathway of tryptophan. 

Milk and eggs are considered to combat pellagra due to 

their high tryptophan content. Primary deficiency occurs 

in areas where maize forms the bulk of the diet. Niacin is 

found in the bound form in maize, making it not easily 

absorbed. Secondary deficiency occurs in cases of diarrhea, 

prolonged isoniazid therapy, cirrhosis, or in postoperative 

patients who have poor supplementation. Deficiency 

results in pellagra, characterized by diarrhea, 

dementia, and dermatitis. Skin changes may resemble 

sunburn and may appear in characteristic patterns around 

the neck (Casal necklace). Diagnosis primarily is clinical. 

Niacin should be administered at a dose of 50 to 

300 mg/d with a balanced diet and supplemented with 

other vitamins. 

Pyridoxine (Vitamin B 6 ) 

Pyridoxine is found in yeast, rice polishings, and cereals. 

Dietary sources are important because synthesis is limited 

in humans. Vitamin B 6 serves as a coenzyme in the 

metabolism and transfer of amino acids. Primary deficiency 

is rare, but secondary deficiency due to malabsorption, 

diarrhea, or drugs such as isoniazid can occur. 

Deficiency causes refractory seizures, peripheral neuritis, 

dermatitis, and microcytic anemia. A large amount of 

xanthurenic acid in the urine following administration of 

100 mg of tryptophan confirms pyridoxine deficiency. 

For seizures, 100 mg of pyridoxine is injected intramuscularly. 

In vitamin B 6 -dependent children, a 10- to 

100-mg oral dose may be required. 

Vitamin B 12 (Cobalamin) 

Microorganisms in animals produce B 12 ; humans cannot 

make the vitamin. The vitamin combines with intrinsic 

factor (IF) in the stomach, and the complex is absorbed 

in the terminal ileum. It then is bound to transcobalamin 

(TC) II and enters the cell. Vitamin B 12 is stored in the 

liver. Besides its role in DNA synthesis and methyl group 

transfer, this vitamin is important for the maintenance of 

normal hemopoiesis. Deficiency occurs in strict vegetarians; 

following resection of terminal ileum or stomach; 

and with inhibition of B 12 -IF complex, abnormalities of 

the receptors on terminal ileum, or abnormalities of 

TCII. 

Juvenile pernicious anemia is an autosomal recessive 

disorder caused by deficiency of gastric intrinsic factor. 

Symptoms occur from 9 to 11 years of age, when patients 

present with irritability, anorexia, and a painful red 

tongue. Ataxia, decreased reflexes, clonus, and coma may 

occur. A macrocytic megaloblastic anemia occurs. Young 

infants who have macrocytic anemia, diarrhea, and failure 

to thrive caused by vitamin B 12 deficiency most likely are 

born to mothers who are vitamin B 12 -deficient. Usual 

causes of maternal deficiency are dietary inadequacy 

(a total vegan diet) or other medical conditions causing 

malabsorption of the vitamin. Older children can develop 

the deficiency due to lack of hepatic stores following 

catastrophic conditions such as short bowel syndrome 

or diseases that result in damage to the terminal 

ileum (Crohn disease). Anemia, hypersegmented neutrophils, 

low serum concentrations of vitamin B 12 , elevated 

levels of lactate dehydrogenase, and excessive secretions of 

methylmalonic acid in the urine are seen. Results of the 

Schilling test, which assesses the absorption of vitamin B 12 , 

may remain abnormal even after therapy. 

A prompt hematologic response within 2 to 4 days 

occurs with the administration of 1 mg of vitamin B 12 . 

Folate 

Folate is important in the maturation of red blood cells 

and participates in the synthesis of nucleic acids. It is 

absorbed throughout the small intestine. Deficiency occurs 

in very low-birthweight infants and following intestinal 

surgery with secondary bacterial overgrowth. Other 

diseases that cause chronic enteritis, such as chronic 

infections, celiac disease, and Crohn disease, also result in 

folate malabsorption. Megaloblastic anemia, irritability, 

chronic diarrhea, and failure to gain weight may occur. 

An oral or parenteral dose of 1 to 5 mg/d may be 

administered when the diagnosis is established. Treating 

pernicious anemia with folate may produce a partial 

response to the anemia without altering the neurologic 

abnormalities. Women of child-bearing age should take 

folate supplements to help decrease the incidence of 

neural tube defects. 

An excess of pyridoxine can cause neuropathy. 

Vitamin C (Ascorbic Acid) 

Case 6 

A 10-month-old boy is brought to the emergency department 

by his 14-year-old mother for irritability. According 


nutrition 

vitamins 

to his mother, the child was fine until 48 hours ago, when he 

was fussier than usual and wanted to be left alone. He has 

had no fever, runny nose, vomiting, or diarrhea. He has 

been taking his milk as usual, although his intake has 

decreased in the past 48 hours. He has been fed evaporated 

milk since birth because the family had no money for formula. 

He has not yet started on solids. On physical examination, 

the child is very irritable, lies with his hips and knees 

flexed, and cries when moved. He has a few petechiae on his 

body but no other findings. Suspecting abuse, the physician 

orders a skeletal survey that shows pencil-thin cortex and a 

ground glass appearance of the bones. Additional testing 

confirms the diagnosis. 


This potent reducing agent is abundantly present in 

citrus fruits, spinach, cauliflower, liver, kidney, and the 

adrenal cortex. It helps form the ground substance 

among cells of the capillary walls, collagen, and osteoid 

tissue; is involved in cellular oxidation (reduction reactions); 

and is required for the normal growth and maturation 

of cells. Scurvy occurs in infants whose mothers 

have a diet deficient in vitamin C and in infants fed 

unsupplemented evaporated milk. Deficiency also occurs 

when there is fever, diarrhea, and protein depletion. 

Irritability, generalized tenderness causing pseudoparalysis, 

frog position of the legs, peripheral edema, swelling 

of gums, scorbutic beads in the ribs, and petechial hemorrhages 

can be seen. Radiographic changes consist of a 

ground glass appearance of the bones, pencil-thin cortex, 

a zone of calcified cartilage at the metaphysis (white line 

of Fraenkel), and a zone of rarefaction proximal to this 

line. A vitamin C level of zero in the buffy layer indicates 

latent scurvy. 


Ascorbic acid (100 to 200 mg/d) promotes quick healing. 

The child in Case 6 was diagnosed with scurvy, and 

treatment was initiated. It is important to note that the 

irritability seen in affected infants often can mimic abuse 

or sepsis, but the history of being fed evaporated milk 

only for this child should raise suspicion for the diagnosis 

of scurvy. 

Effect of Excess 

Excess vitamin C can predispose to oxaluria. 

Suggested Reading 

Barness LA, Curran JS. Vitamin deficiencies and excesses. In: 

Behrman RE, Kliegman R, Jenson HB, eds. Nelson Textbook of 

Pediatrics. Philadelphia, Pa: WB Saunders Co; 1996:172–184 

Gartner LM, Greer FR. Prevention of rickets and vitamin D deficiency: 

new guidelines for vitamin D intake. Pediatrics. 2003; 

111:908–910 

Kumar D, Greer FR. Vitamin K status of premature infants: implications 

for current recommendations. Pediatrics. 2001;108: 

1117–1122 

Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor 

away: scurvy in the year 2000. Pediatrics. 2001;108:E55. Available 

at: http://pediatrics.aappublications.org/cgi/content/ 

full/108/3/e55 

PIR Quiz 

Quiz also available online at www.pedsinreview.org. 

1. Vitamin A deficiency is characterized by: 

A. Excessive tearing. 

B. Loss of vibration sense. 

C. Nyctalopia. 

D. Severe headaches. 

E. Spontaneous hemorrhage. 

2. Vitamin D-resistant rickets (familial hypophosphatemia) is differentiated from vitamin D-deficient rickets by: 

A. Bowing of legs. 

B. Elevation of serum alkaline phosphatase concentrations. 

C. Low phosphate concentration. 

D. Normal serum parathyroid hormone concentration. 

E. Sparing of males. 


nutrition 

vitamins 

3. Of the following, the most specific risk factor for vitamin D-deficient rickets is: 

A. Birth in April. 

B. Excessive sun exposure. 

C. Formula feeding. 

D. Light-colored skin. 

E. Very low birthweight. 

4. Vitamin E deficiency is characterized by: 

A. Cheilosis. 

B. Growth failure. 

C. Muscle weakness. 

D. Spontaneous hemorrhage. 

E. Tetany. 

5. A common finding in both vitamin B 12 deficiency and vitamin K deficiency is: 

A. Anemia. 

B. Ataxia. 

C. Glossitis. 

D. Growth failure. 

E. Hemorrhage. 

Clarifications 

In the October 2005 issue, an error appears on page 378 in Table 2 of the article on Rapid Diagnostic 

Tests for Infectious Diseases Suitable for Office Use. Under Mechanism, the first item should be: 

Detects group A streptococcal antigen (rather than staphylococcal antigen). 

In Case 1 Presentation of the Index of Suspicion in October 2005, the hemoglobin value on page 

371, line 28 should be 10.6 g/dL rather than 1.06 g/dL. 

According to the 2003 Red Book, several changes are required in the In Brief on Antiviral Therapy for 

Influenza Infections that appeared in the November 2005 issue. In the first paragraph, annual 

administration of influenza vaccine is recommended “for all children 6 to 24 months of age” rather than 

“for all children younger than 2 years of age.” In the second paragraph, the statement about the dosage 

of rimantadine, “Children 10 years of age or older may take 100 mg BID” should be expanded to 

“Children 10 years or older weighing at least 40 kg may take 100 mg BID.”

Vitamins - sepeap

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