Vitamin Deficiencies in Children

Vitamin deficiencies remain a major cause of preventable morbidity and mortality in Indian children, and the topic is a perennial NEET PG favourite for its sharp, fact-based questions — eponyms, X-ray signs, biochemical cut-offs, drugs of choice, and national supplementation doses. This note organises every clinically important vitamin (fat-soluble A, D, E, K and water-soluble B-complex and C) into a single exam-ready frame.

Classification of vitamins

Vitamins are micronutrients required in minute amounts and are broadly divided by solubility, which dictates storage, toxicity risk, and deficiency time-course.

Feature	Fat-soluble (A, D, E, K)	Water-soluble (B-complex, C)
Storage	Liver/adipose; large reserves	Minimal (except B12, stored in liver ~3-5 yrs)
Deficiency onset	Slow (months-years)	Rapid (weeks), B12 the exception
Toxicity	Common (hypervitaminosis A, D)	Rare; excess excreted in urine
Absorption	Needs bile salts + fat	Direct (B12 needs intrinsic factor)
Excretion	Bile/faeces	Urine

High-yield: Fat-soluble vitamins cause hypervitaminosis (A and D are the classic toxic ones); water-soluble vitamins are generally safe in excess, the notable exception being pyridoxine (B6) which causes a sensory peripheral neuropathy on chronic overdose.

Vitamin D deficiency — Rickets

Rickets is defective mineralisation of the growing bone (epiphyseal growth plate); in adults the same process after epiphyseal fusion is osteomalacia. The peak age is 6 months to 2 years — a period of rapid growth, low stores, and exclusive breastfeeding (breast milk is poor in vitamin D).

Pathophysiology

Vitamin D → 25-hydroxylation in liver → 1-α-hydroxylation in kidney (by 1-α-hydroxylase, stimulated by PTH and low phosphate) → 1,25-dihydroxycholecalciferol (calcitriol), the active form. Deficiency → low gut Ca²⁺/PO₄³⁻ absorption → hypocalcaemia → secondary hyperparathyroidism → phosphaturia → low phosphate → impaired mineralisation.

Vitamin D → liver (25-OH) → kidney (1,25-(OH)₂) → ↑Ca/PO₄ absorption → bone mineralisation

Clinical features

• Skull: craniotabes (earliest sign, ping-pong ball feel of occiput), frontal bossing, delayed fontanelle closure.
• Chest: rachitic rosary (beading at costochondral junctions), Harrison's sulcus (groove at diaphragm insertion), pigeon chest.
• Wrist: widening of wrists (classic clinical sign), double malleoli (Marfan's sign).
• Legs: genu varum (bow legs) once weight-bearing; genu valgum (knock knees) in older children.
• Spine: kyphoscoliosis, pot belly (hypotonia).
• Dental: delayed dentition, enamel hypoplasia.
• Delayed motor milestones, tetany/seizures if severe hypocalcaemia.

X-ray signs (very high yield)

Best seen at the wrist (lower end of radius and ulna):

• Cupping, splaying (widening), and fraying of the metaphysis.
• Widened epiphyseal plate and increased distance between epiphysis and metaphysis.
• Loss of provisional zone of calcification; osteopenia; Looser's zones (pseudofractures) in osteomalacia.

Biochemistry	Nutritional rickets	Vitamin D-resistant (hypophosphataemic)
Serum calcium	Low/normal	Normal
Serum phosphate	Low	Markedly low
Alkaline phosphatase	High	High
PTH	High (secondary)	Normal
25-OH vitamin D	Low	Normal
Inheritance	Acquired (dietary/sunlight)	X-linked dominant (PHEX mutation, ↑FGF23)

High-yield: Alkaline phosphatase is raised in ALL active rickets and is the most sensitive early biochemical marker. The investigation of choice for diagnosis is serum 25-hydroxyvitamin D (best reflects body stores); X-ray wrist confirms bony changes.

Treatment

• Stoss therapy: single large dose 6 lakh (600,000) IU vitamin D oral/IM, OR
• Daily 2000–5000 IU for 6–12 weeks, then maintenance 400 IU/day.
• Ensure adequate calcium (elemental Ca 30–75 mg/kg/day).
• Radiological healing: line of provisional calcification reappears within 2–4 weeks; ALP normalises later.
• Prophylaxis: 400 IU/day vitamin D for all infants (exclusively breastfed especially).

Refractory rickets — think of:

1. Vitamin D-dependent rickets type 1 (1-α-hydroxylase deficiency) → treat with calcitriol.
2. Type 2 (receptor defect) → very high calcitriol, alopecia.
3. X-linked hypophosphataemic rickets → oral phosphate + calcitriol; burosumab (anti-FGF23) is newer.
4. Renal tubular acidosis, chronic renal failure (renal osteodystrophy).

Vitamin A deficiency (VAD) — Xerophthalmia

Vitamin A (retinol) is essential for rhodopsin synthesis (vision in dim light), epithelial integrity, and immunity. VAD is a leading cause of preventable childhood blindness worldwide.

WHO Xerophthalmia classification (memorise the order)

Stage	Sign	Note
XN	Night blindness (nyctalopia)	Earliest symptom
X1A	Conjunctival xerosis
X1B	Bitot's spots	Foamy, triangular, on temporal bulbar conjunctiva; pathognomonic
X2	Corneal xerosis
X3A	Corneal ulceration <1/3 cornea	Reversible
X3B	Keratomalacia (≥1/3, liquefaction)	Irreversible, blinding
XS	Corneal scar
XF	Xerophthalmic fundus

High-yield: Night blindness (XN) is the earliest sign; Bitot's spots (X1B) are pathognomonic; keratomalacia (X3B) is the blinding, irreversible stage. Bitot's spots are due to keratinised epithelium with Corynebacterium xerosis.

Other features: follicular hyperkeratosis (phrynoderma — toad skin), increased infections (measles worsens VAD and vice versa), growth retardation.

Treatment — WHO/IAP vitamin A schedule (by age)

• >1 year / >8 kg: 200,000 IU orally on Day 1, Day 2, and Day 14.
• 6–12 months / <8 kg: 100,000 IU on the same schedule.
• <6 months: 50,000 IU.

High-yield: Give vitamin A to all children with measles (reduces mortality). National Prophylaxis Programme: 9 doses — first dose 1 lakh IU at 9 months with measles vaccine, then 2 lakh IU every 6 months up to 5 years.

Toxicity: Acute → pseudotumor cerebri (raised ICP, bulging fontanelle, vomiting). Chronic → bone pain, hepatomegaly, alopecia. Teratogenic — avoid high-dose/retinoids in pregnancy.

Vitamin C deficiency — Scurvy

Vitamin C (ascorbic acid) is a cofactor for prolyl and lysyl hydroxylase, needed for collagen cross-linking. Deficiency → fragile capillaries and defective connective tissue. Onset after ~1–3 months of deficient intake; classic in infants fed boiled/processed milk without fruit/vegetables.

Clinical features

• Bleeding: perifollicular haemorrhages, gum bleeding/swelling (only in dentate children — none in edentulous infants), subperiosteal haemorrhage (painful legs, "pseudoparalysis").
• Frog-leg position / pseudoparalysis — infant lies still with hips/knees flexed, externally rotated, due to pain.
• Costochondral beading (scorbutic rosary) — note: the junction is sharp/angular with sternum displaced backward, vs the rounded rachitic rosary.
• Poor wound healing, corkscrew hairs, woody oedema of legs, anaemia.

X-ray (long bone, knee) signs — classic eponyms

Sign	Description
White line of Frankel	Dense zone of provisional calcification
Trümmerfeld / scurvy line	Lucent band beneath Frankel's line (zone of weakness)
Pelkan spurs	Lateral metaphyseal spurs
Wimberger's ring	Sclerotic ring around epiphysis (ground-glass)
Corner sign	Metaphyseal angle defect

High-yield: Wimberger's ring is a NEET-PG favourite eponym for scurvy. Do not confuse with Wimberger's sign in congenital syphilis (destruction of the medial proximal tibial metaphysis).

Treatment: Vitamin C 100–200 mg/day for 1–3 months; dramatic response within days.

Niacin (B3) deficiency — Pellagra

Niacin can be synthesised from tryptophan (60 mg tryptophan → 1 mg niacin). Deficiency seen in maize-eating populations (maize niacin is bound/unavailable), Hartnup disease (defective tryptophan absorption), and carcinoid syndrome (tryptophan diverted to serotonin), and with isoniazid.

The 4 D's of pellagra (mnemonic)

Dermatitis (photosensitive, symmetrical; Casal's necklace around neck) → Diarrhoea → Dementia → Death if untreated.

High-yield: Casal's necklace = pigmented, scaly dermatitis around the neck, pathognomonic of pellagra. Treat with niacin (nicotinamide) 100–300 mg/day.

Thiamine (B1) deficiency — Beriberi & Wernicke's

Thiamine is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase.

Type	Features
Dry beriberi	Symmetrical peripheral neuropathy, wrist/foot drop
Wet beriberi	High-output cardiac failure, oedema, tachycardia
Infantile beriberi	In breastfed infants of thiamine-deficient mothers; aphonia (hoarse/aphonic cry), cardiac failure, 2–4 months
Wernicke encephalopathy	Triad: ophthalmoplegia + ataxia + confusion
Korsakoff psychosis	Anterograde amnesia, confabulation (irreversible)

High-yield: In suspected Wernicke's, give thiamine BEFORE glucose — a glucose load in a thiamine-deficient patient precipitates/worsens Wernicke encephalopathy. The mnemonic for Wernicke triad is "COAT": Confusion, Ophthalmoplegia, Ataxia, Thiamine."

Megaloblastic anaemia — Vitamin B12 & Folate

Both B12 (cobalamin) and folate are needed for DNA synthesis; deficiency → megaloblastic (macrocytic) anaemia with MCV >100 fl, hypersegmented neutrophils (>5 lobes), and ineffective erythropoiesis (pancytopenia, raised LDH/bilirubin).

Feature	Vitamin B12 deficiency	Folate deficiency
Stores	3–5 years (liver)	~3–4 months
Source	Animal foods only	Green leafy vegetables
Absorption	Terminal ileum + intrinsic factor	Jejunum
Neuro signs	Yes — SACD, neuropathy	No (usually)
Methylmalonic acid	Raised	Normal
Homocysteine	Raised	Raised

High-yield: Subacute combined degeneration (SACD) of dorsal + lateral columns occurs ONLY in B12 deficiency. Giving folate alone in B12 deficiency corrects anaemia but precipitates/worsens neurological damage — always confirm/replace B12 first.

Paediatric causes: maternal deficiency in exclusively breastfed infants of vegan/B12-deficient mothers, juvenile pernicious anaemia, Imerslund-Gräsbeck syndrome (selective B12 malabsorption + proteinuria). Treatment: parenteral B12 (hydroxocobalamin/cyanocobalamin) for B12; oral folic acid for folate.

Vitamin K & Vitamin E

• Vitamin K (cofactor for clotting factors II, VII, IX, X, protein C & S) deficiency → Vitamin K Deficiency Bleeding (VKDB) of the newborn (formerly haemorrhagic disease of newborn). Prevented by 1 mg IM vitamin K at birth. PT prolonged first.
• Vitamin E (tocopherol, antioxidant) deficiency → haemolytic anaemia in preterms, spinocerebellar ataxia, peripheral neuropathy, retinopathy. Seen in fat malabsorption/abetalipoproteinaemia.

Key biochemical cut-offs & investigations of choice

Vitamin	Investigation of choice / marker
Vitamin D	Serum 25-OH vitamin D (<20 ng/ml deficient; <12 severe)
Rickets activity	Serum alkaline phosphatase (raised)
Vitamin A	Serum retinol (<20 µg/dl deficient)
Vitamin C	Leucocyte ascorbic acid
B12 deficiency	Serum B12; methylmalonic acid (more sensitive)
Thiamine	Erythrocyte transketolase activity

Complications

• Rickets: permanent skeletal deformity (bow legs), short stature, pelvic deformity (obstructed labour later in girls), hypocalcaemic seizures, dilated cardiomyopathy (rare).
• VAD: irreversible blindness (keratomalacia), increased infection mortality.
• Scurvy: intracranial/subperiosteal haemorrhage, growth arrest.
• B12: irreversible neuropsychiatric deficits if treated late.
• Pellagra/Wernicke: death and permanent dementia/Korsakoff if untreated.

Key differentials

• Bow legs: physiological bowing (resolves by 2 yrs), rickets, Blount's disease (tibia vara), skeletal dysplasia.
• Pseudoparalysis of limbs: scurvy, congenital syphilis (Parrot's pseudoparalysis), osteomyelitis, NAI (non-accidental injury).
• Costochondral beading: rickets (rounded) vs scurvy (sharp/angular).
• Macrocytic anaemia: B12/folate, hypothyroidism, liver disease, reticulocytosis.

Recently asked / exam angle

• "Earliest X-ray sign / clinical sign of rickets" → craniotabes (clinical), wrist cupping/fraying (X-ray); earliest biochemical → raised ALP.
• "Best investigation for vitamin D status" → serum 25-OH vitamin D.
• "Pathognomonic sign of vitamin A deficiency" → Bitot's spots.
• "Wimberger's RING vs Wimberger's SIGN" → scurvy vs congenital syphilis (frequently paired to confuse).
• "Casal's necklace" → pellagra (niacin/B3).
• "Give thiamine before glucose" → Wernicke encephalopathy.
• "Folate alone worsens neuro deficit" → B12 deficiency.
• National programme doses: vitamin A 1 lakh IU at 9 months, then 2 lakh every 6 months; vitamin D prophylaxis 400 IU/day; vitamin K 1 mg IM at birth.
• Stoss therapy dose for rickets → 6 lakh IU.
• Hypophosphataemic rickets → X-linked dominant, FGF23, low phosphate, normal calcium/PTH.

Rapid revision

1. Rickets peak age 6 months–2 years; ALP raised in all active rickets.
2. Investigation of choice for vitamin D = serum 25-OH-D; X-ray wrist shows cupping, splaying, fraying.
3. Stoss therapy = single 6 lakh IU vitamin D; daily prophylaxis 400 IU.
4. Bitot's spots = pathognomonic of VAD; night blindness earliest, keratomalacia blinding.
5. Vitamin A at 9 months 1 lakh IU; always give vitamin A in measles.
6. Scurvy = collagen defect → Wimberger's ring, Pelkan spurs, Frankel's line; pseudoparalysis/frog-leg.
7. Wimberger's SIGN (medial tibial metaphysis) = congenital syphilis, NOT scurvy.
8. Pellagra (B3) = 4 D's + Casal's necklace; seen in maize diet, Hartnup, carcinoid, INH.
9. Wernicke = ophthalmoplegia + ataxia + confusion; thiamine before glucose.
10. B12 deficiency → SACD + raised methylmalonic acid; never give folate alone.
11. Vitamin K 1 mg IM at birth prevents VKDB; deficiency prolongs PT first.
12. Vitamin E deficiency → haemolytic anaemia in preterm + spinocerebellar ataxia.