Overview of micronutrient deficiency disorders and clinical signs

By: Darayus P.Gazder

All micronutrients are important for:1) Growth,2) Health,3) Development.

BACKGROUND

Vitamins are organic substances that are essential for several enzymatic functions in human metabolism

A compound is called vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet.

Functions Acts as hormones (vitamin D)Acts as antioxidant (vitamin E) Acts as mediators of cell signalling and regulators of cell and tissue growth and differentiation(vitamin A)

Acts as precusors for enzyme cofactor biomolecules(coenzymes) that help act as catalysts and substrates in metabolism

VITAMINS

Vitamins are classified according to solubility into fat soluble & water soluble.

13 vitamins are known, 4 fat soluble (KEDA) & 9 water soluble (C, Folate & the B group).

VITAMINS

Water soluble-dissolve easily in water readily excreted from the body.

Fat soluble-absorbed through the intestinal tract with the help of lipids(fats).

VITAMIN A-Vitamin A is a generic term for many related compounds. Retinol (alcohol), Retinal (aldehyde) are often called preformed vitamin A. Retinal can be converted by the body to retinoic acid which is known to affect gene transcription.Body can convert b-caroteneto retinol, thus called provitamin A.

FUNCTIONS• Immunity: important for activation of T lymphocyte, maturation of WBC & integrity of physiological barrier.

• Vision: integrity of eye & formation of rodopsin necessary for dark adaptation.

• Red blood cell production

• Regulation of gene expression: vital to cell differentiation & physiologic processes

• Growth & development

Animal Foods

Plant Foods

Cod liver oil Sweet potatoLiver & kidney

Carrots

Egg Spinach

ButterMilk & cheese

RICH DIETARY SOURCES

Vitamin A deficiency• Deficiency of vitamin A leads to:1. Ocular change- Night blindness &

xerophthalmia2. Extra ocular changesGrowth retardationAcquired immune deficiencyAnemia

WHO CLASSIFICATION OF XEROPTHALMIAPRIMARY SIGNS SECONDARY SIGNS

X1A: Conjunctival xerosis

X1B: Bitot’s spot X2: Corneal xerosis X3A: Corneal ulceration X3 B: Keratomalacia

XN: Night blindness XF: Fundal changes XS: Corneal scarring

Xeropthalmia

Bitots spots (X1B) are foamy white areas on the white of the eye.

Corneal Xerosis(X2) Keratomalacia (X3)

INVESTIGATIONS:

Clinical evaluation(Skin, Eyes, Growth)Serum retinol <20 mcg/dL;Molar ratio of retinol:RBP(Retinol

binding protein) <0.7 is also diagnostic

Treatment

• Overall mortality is reduced by 23%• Death from measles is reduced by 50%• Death from diarrhea is reduced by 40%

TOXICITY- Children and adults ingesting >50,000 IU/day for several month.

• Vitamin A in excess leads to:• Dermatitis with xanthosis cutis• Hepatosplenomegaly• Fatigue, malaise, anorexia, vomiting• Bone pain & increased risk of fracture

• Pseudotumor Cerebri• Xray-hyperostosis of the shafts of long bones

VITAMIN D Vitamin D comprises a group of sterols; the

most important of which are cholecalciferol (vitamin D3) & ergosterol (vitamin D2).

Humans & animal utilize only vitamin D3 & they can produce it inside their bodies from cholesterol.

Cholesterol is converted to 7-dehydro-cholesterol (7DC), which is a precursor of vitamin D3.

FUNCTIONS

• Calcium metabolism: vitamin D enhances Calcium absorption in the gut & renal tubules.

• Cell differentiation: particularly of collagen & skin epithelium

• Immunity: important for Cell Mediated Immunity & coordination of the immune response.

Sources of Vitamin DSunlight is the most important

source Fish liver oil Fish & sea food (herring & salmon) Eggs Plants do not contain vitamin D3 Human milk deficient in vit. D,

contains only 30-40 IU per liter mostly from 25(OH)D3

Vitamin D deficiency

•Deficiency of vitamin D leads to: Rickets in small children. Osteomalacia

RICKETSLack of adequate mineralisation of growing bone

CLINICAL FEATURES

RICKETSSign and symptoms-• Skeletal deformity-bowed legs(genu varum) in toddlers, knock knees (genu valgum) in older children, craniotabes (soft skull), spinal and pelvic deformities, growth disturbances, costochondral swelling(rickety rosary), harrisons groove, greenstick fractures, bone pain and tenderness, muscle weakness and dental problems.

INVESTIGATIONSRadiologic changes-loss of normal zone of provisional calcification adjacent to metaphysis.

Widening of the growth plate.Splaying and cupping of metaphysis.Generalized reduction in bone density.Low circulating levels of 25(OH)D3.Elevated serum alkaline phosphate.Calcium level may be normal or lowPhosphate level usually are unchanged or low.

Metaphyseal cupping and fraying in thedistal radius and ulna in rickets

TREATMENT

AAP: 400IU/day for all breastfed infants, beginning in 1st 2months of life and continue until infant is receiving >500ml/day of vitamin of formula or vitamin D fortified milk

Rickets: 1600-5000IU of VitD3 per day

Stross therapy:

TOXICITY• Hypervitaminosis D – infants-2,000-3,000 IU/day,

adults-10,000 IU/day for several months.causes hypercalcemia,hyperphosphatemia, hypertension which manifest as:Nausea & vomitingExcessive thirst & polyuriaSevere itchingJoint & muscle painsAzotemia, nephrolithiasis, ectopic calcification.Disorientation & coma.

Vitamin K It is a cofactor of the enzyme that catalyzes one

step in the formation of prothrombin. Needed for the generation of several clotting

factors in the liver. Source- green leafy vegetables. Deficiency-coagulation defect due to

hypoprothrombinemia and deficiency of factor VII resulting in hemorrhagic disease of the newborn.

1mg IM –newborn. In severe deficiency-2.5 to 5 mg/day parenterally.

Vitamin C - Ascorbic Acid Humans are among the few species that

cannot synthesize vitamin C and must obtain it from food

Manufacture of collagen Helps support and protect blood vessels,

bones, joints, organs and muscles Protective barrier against infection and

disease Promotes healing of wounds, fractures and

bruises Sources

Citrus fruits, strawberries, kiwifruit, blackcurrants, papaya, and vegetables

Scurvy – Signs & Symptoms Small blood vessels fragile Gums reddened and bleed easily Teeth loose Joint pains Scorbutic rosary: Costochondral junction is more angular

and has a sharper step-off  Dry scaly skin Lower wound-healing, increased susceptibility to

infections, and defects in bone development in children

Legs assume a “frog like position”(Hips and knees are semiflexed with the feet rotated outwards)

Diagnosis

History+Clinical Features Xray appearance of long bones:1. Ground glass appearance of bones2. Cortex is reduced to “Pencil Point” thinness3. There is white line of Fraenkel (An irregular but

thickened white line at metaphysis representing the zone of well calcified cartilage

Low levels of Vitamin C

Treatment

Prevented by a diet of Vitamin C Daily therapeutic dose of Vitamin C is 100-200mg

or more. Daily requirement is 45-60mg/day in children

Thiamin – Vitamin B1

What it does in the body energy production and carbohydrate and fatty

acid metabolism vital for normal development, growth,

reproduction, healthy skin and hair, blood production and immune function

Deficiency due to diets of polished rice

Beri Beri- Signs & Symptoms Develop within 12 weeks Dry Beriberi peripheral neuropathy

Difficulty walking and paralysis of the legs Reduced knee jerk and other tendon reflexes, foot

and wrist drop Progressive, severe weakness and wasting of

muscles Wet Beriberi cardiopathy

Edema of legs, trunk and face Congestive heart failure (cause of death)

Wrist & foot drop:Dry Beri Beri

Edema:Wet Beri Beri

Riboflavin Deficiency

Deficiency is rare and often occurs with other B vitamin deficiencies

Several months for symptoms to occur Burning, itching of eyes Angular stomatitis Cheilosis

Swelling and shallow ulcerations of lips Glossitis

Riboflavin deficiency

Angular stomatitis Glossitis

Niacin – Vitamin B3

Essential for healthy skin, tongue, digestive tract tissues, and RBC formation

Processing of grains removes most of their niacin content so flour is enriched with the vitamin

Pellagra – Signs & Symptoms ‘Three Ds’: diarrhea, dermatitis and dementia Reddish skin rash on the face, hands and

feet which becomes rough and dark when exposed to sunlight (pellagrous dermatosis) acute: red, swollen with itching, cracking,

burning, and exudate chronic: dry, rough, thickened and scaly with

brown pigmentation dementia, tremors, irritability, anxiety,

confusion and depression

Pellagra Dermatitis

Anemia

Iron deficiency is the most common cause of anemia and most common preventable nutritional deficiency.

Causes:Nutritional

Mother anemic Increased Fe demands:

(Preterm,IUGR,Cyanotic heart disease)

Prolonged breastfeeding, cow milk

Malabsorption Poor weaning

Blood Loss1. Neonates: Fetomaternal transfusions Twin to twin transfusions Bleeding from umblical cord Hemorrhagic disease of

Newborn

2. Children: Hookworm infestation Rectal polys IBD

Anemia- Signs & Symptoms Symptoms Tiredness/ Fatigue/ Headache/Breathlessness Signs Pallor: Pale conjunctivae, palms, tongue, lips, skin,

Spoon shaped nails. Tachycardia, Systolic murmur If Hb<3, check for signs of CHF

Investigations: CBC: 1) Hemoglobin <11.0 g/dL

MVC/ MCH/ MCHC are all decreased Reticulocyte count: Normal or minimally elevated Peripheral blood smear: Microcytic hypochromic anemia Serum Fe levels: Decreased TIBC: Increased Serum ferritin levels: Decreased

Normal Blood Film

MICROCYTES

HYPOCHROMIA

Anemia- Treatment

Dietary counseling: Infants fortified milk formula less than 1yr of age

Dietary diversification Foods that are rich in iron include: Meat/ Fortified cereals/ Spinach/Lentils and beans

Iron supplements Mild to moderate anemia: 3-6mg/kg/day of iron (3-5 months)

Severe anemia and cardiac decompensation: Start blood transfusions, packed RBC’s: (2-3ml/kg)

Zinc Deficiency

Zinc essential for the function of many enzymes and metabolic processes

Zinc deficiency is common in developing countries with high mortality

Zinc commonly the most deficient nutrient in complementary food mixtures fed to infants during weaning

Zinc interventions are among those proposed to help reduce child deaths globally by 63% (Lancet, 2003)

Zinc Deficiency- Signs & Symptoms

Skin lesions Immune impairment Diarrhea Poor growth Acrodermatitis enteropathica: AR disorder (defect of Zn absorption) Begins within 2-4 weeks of weaning Perioral/ Perianal dermatitis/ Failure to thrive

Zinc Deficiency- Assessment

No simple, quantitative biochemical test of zinc status Serum Zinc

• Can fluctuate as much as 20% in 24-hour period• Levels decreased during acute infections• Expensive

Hair zinc analysis

Zinc Deficiency- Treatment

Regular zinc supplements can greatly reduce common infant morbidities in developing countries • Adjunct treatment of diarrhea

-10 mg/day for infants below 6 months, -20mg/day of zinc for 10-14

days(>6months)

Zinc deficiency commonly coexists with other micronutrient deficiencies including iron, making single supplements inappropriate

Emperical trial of Zinc supplementation(1ug/kg/day) is safe and reasonable