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Enhanced Notes: Clinical Features of Vitamin B Deficiency

Based on Ghai Textbook of Paediatrics (with supplementation from Harrison's Principles, Tietz Textbook of Laboratory Medicine, Bradley and Daroff's Neurology, and Harriet Lane Handbook)

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1. THIAMINE (Vitamin B₁) DEFICIENCY — BERIBERI

Biochemical Role

• Carbohydrate metabolism (pyruvate dehydrogenase, α-ketoglutarate dehydrogenase)
• Amino acid catabolism
• Pentose phosphate pathway (via transketolase)

Causes / At-Risk Groups

• Dietary: Excessive intake of polished/milled rice (removes the thiamine-rich germ layer — this became widespread in the late 1800s when polishing rice became mechanised)
• Alcohol: Reduces absorption, impairs synthesis of TPP, increases urinary excretion
• Other groups: Prolonged vomiting (hyperemesis gravidarum), total parenteral nutrition without supplementation, raw fish consumption (contains thiaminases that destroy the vitamin), tea (contains anti-thiamine factors)
• Paediatric note: Maternal thiamine deficiency can cause infantile beriberi in exclusively breastfed infants

Etymology

Clinical Forms

• Wernicke's encephalopathy: Ophthalmoplegia, ataxia, confusion
• Korsakoff syndrome: Amnesic psychosis, confabulation

Infantile Beriberi

• Appears suddenly and severely, often with cardiac failure and cyanosis
• Linked to maternal deficiency in breastfed infants

Diagnosis

• Blood/urine assays for thiamine are unreliable
• Best test: Erythrocyte transketolase activity + % increase with added TPP in vitro (TPP effect)
• Nerve conduction studies show axonal sensorimotor polyneuropathy

Treatment

• Thiamine 100 mg/day IV or IM until nutrition is restored
• Cardiac manifestations respond dramatically and quickly
• Neurological recovery is variable and less complete
• Always give thiamine before glucose in malnourished patients — carbohydrate repletion without thiamine can precipitate acute deficiency with lactic acidosis

Thiamine-Responsive Genetic Disorders (Paediatric High-Yield)

• Thiamine-responsive megaloblastic anaemia (TRMA): Mutation in SLC19A2 gene (thiamine transporter)
• Thiamine-responsive PDH complex deficiency: Presents with lactic acidosis
• Thiamine-responsive MSUD variant: Branched-chain ketoacid dehydrogenase deficiency
• Treatment dose for these: 5–20 mg/day of thiamine

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2. NIACIN (Vitamin B₃) DEFICIENCY — PELLAGRA

Biochemical Role

Tryptophan–Niacin Relationship (HIGH YIELD)

• Tryptophan can be converted to niacin at a ratio of 60:1 by weight
• This conversion requires Vitamin B₆, riboflavin, and iron as cofactors
• Deficiency of any of these cofactors, or diversion of tryptophan elsewhere, can precipitate pellagra

Causes

Exam Tip: Hartnup disease produces a pellagra-like rash in the absence of dietary niacin deficiency — a key differential. The mechanism is impaired tryptophan transport, reducing endogenous niacin synthesis.

Clinical Features — "The 4 Ds"

• Photosensitive rash on sun-exposed areas
• Characteristic sign: Casal's Necklace — a hyperpigmented, scaly, thickened rash forming a collar around the neck
• Skin is initially erythematous, then becomes hyperpigmented and desquamating
• Can also occur on dorsum of hands, feet, and any sun-exposed surface

• Due to proctitis and malabsorption from intestinal mucosal involvement
• Early symptoms also include anorexia, abdominal pain, vomiting
• Bright red glossitis is an early and notable finding (before skin changes appear in some patients)

• Depression, irritability, memory loss, confusion, seizures
• Early onset, progressive
• Reduced cellular NAD⁺ is implicated in cognitive decline

Sequence to remember: Symptoms appear in order — glossitis → dermatitis → GI symptoms → neuropsychiatric → death

Treatment

• Nicotinamide (preferred) or nicotinic acid 100–200 mg orally three times daily for up to 4 weeks
• Nicotinamide is preferred because it lacks the flushing side effect of nicotinic acid

Pellagra-like Conditions (Differentials)

• Hartnup disease
• Carcinoid syndrome
• Prolonged isoniazid use
• Prolonged 5-fluorouracil use (inhibits tryptophan → niacin conversion)

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3. PYRIDOXINE (Vitamin B₆) DEFICIENCY

Biochemical Role

• Amino acid metabolism (transamination, decarboxylation)
• Neurotransmitter synthesis: GABA (from glutamate), serotonin (from tryptophan), dopamine (from DOPA)
• Haem synthesis
• Tryptophan → niacin conversion (explains overlap with pellagra)

Causes

• Isoniazid (INH): Most important drug cause — INH competitively inhibits pyridoxal phosphate. A trial dose of pyridoxine 100 mg is given to any child on INH with suspected deficiency.
• Penicillamine, cycloserine, hydralazine (all act by inactivating PLP)
• Poor dietary intake

Exam Tip: The drug most classically associated with pyridoxine deficiency is Isoniazid (anti-TB drug). Always co-prescribe pyridoxine with INH in paediatric patients, especially malnourished ones.

Clinical Features by Age

• Refractory seizures — the hallmark. Due to reduced GABA synthesis (GABA is produced from glutamate by a PLP-dependent enzyme, glutamate decarboxylase)
• Pyridoxine-dependent epilepsy (PDE): A rare genetic disorder (ALDH7A1 mutation) where seizures are completely dependent on high-dose pyridoxine
• Diagnostic test: Administer IV pyridoxine 100 mg during a seizure — seizures stop within minutes if pyridoxine-dependent

• Peripheral neuropathy (sensorimotor)
• Anaemia (microcytic, hypochromic — due to impaired haem synthesis)
• Dermatitis (seborrheic-like)
• Glossitis and cheilosis

Treatment

• Prophylaxis with INH: Pyridoxine 1–2 mg/kg/day
• Pyridoxine-dependent seizures: High-dose pyridoxine 15–30 mg/kg/day (lifelong)

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4. RIBOFLAVIN (Vitamin B₂) DEFICIENCY — ARIBOFLAVINOSIS

Biochemical Role

Important: Riboflavin is required for the conversion of tryptophan → niacin and for pyridoxine metabolism. Riboflavin deficiency can therefore precipitate or worsen pellagra and B₆ deficiency — this is the reason these deficiencies commonly co-occur.

Causes

• Usually co-occurs with other water-soluble vitamin deficiencies
• Alcoholism, anorexia, malabsorption syndromes
• Phototherapy in neonates (light degrades riboflavin)
• Phenothiazines and some antimalarials interfere with riboflavin metabolism

Clinical Features (Mnemonic: "GASCPP")

• Normochromic, normocytic anaemia (due to impaired erythropoiesis)
• Hypersplenomegaly (rare)
• Peripheral neuropathy (contribution controversial)

Magenta Tongue

Treatment

• Dietary correction: Riboflavin is found in milk, dairy, meat, eggs, leafy vegetables, and fortified grains
• Oral riboflavin supplementation: 3–10 mg/day in children

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QUICK COMPARISON TABLE — Vitamin B Deficiencies

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IMPORTANT ADDITIONAL POINTS FOR EXAMS

1. Isoniazid affects BOTH niacin and pyridoxine — it is a structural analogue of niacin AND inhibits pyridoxal phosphate. Always co-prescribe pyridoxine with INH.
2. Hartnup disease (autosomal recessive) — impaired neutral amino acid transport (especially tryptophan) → pellagra-like rash but NOT true niacin deficiency. Triggered or worsened by corn diet and sunlight exposure.
3. Wet vs Dry Beriberi distinction is not absolute — it depends on degree of exertion and caloric intake. With high exertion and high carbs → wet; with inactivity and caloric restriction → dry.
4. Riboflavin deficiency facilitates pellagra because riboflavin (as FAD) is required in the pathway converting tryptophan to niacin. This is why famine-related pellagra is multi-deficiency in origin.
5. Phototherapy in neonates receiving treatment for hyperbilirubinemia degrades riboflavin — supplement accordingly.
6. Neonatal pyridoxine-dependent seizures are a classic exam scenario: seizures not responding to standard antiepileptics → give IV pyridoxine 100 mg → dramatic cessation confirms diagnosis.

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