SN5 SHORT NOTE 5M ★ High-yield

Write a short note on pellagra.

Biochemistry · 1st Professional — Pre-Clinical

Pellagra = the deficiency disease of niacin (vitamin B3) or of its precursor tryptophan, characterised by the three Ds.

Feature	Description
Dermatitis	Symmetrical, on sun-exposed areas; erythema then pigmentation, thickening and scaling. Casal's necklace around the neck; "glove and boot" on limbs; butterfly on the face
Diarrhoea	With glossitis, stomatitis, angular cheilitis; a raw beefy red tongue; achlorhydria
Dementia	Irritability, insomnia, depression, memory loss, confusion, hallucinations, frank psychosis
Death	If untreated

The dermatitis is photosensitive because niacin deficiency impairs the repair of ultraviolet damage — this is why it spares covered skin

Niacin forms NAD+ and NADP+, required by over 200 dehydrogenases
Deficiency impairs energy metabolism, the HMP shunt and DNA repair (NAD is the substrate for PARP)
Rapidly dividing and high-energy tissues suffer first — skin, gut mucosa and brain, which is precisely the pattern of the three Ds
60 mg tryptophan yields 1 mg niacin; the conversion needs vitamin B6, B2 and iron

Type	Cause
Primary (dietary)	Maize-based diets — maize niacin is bound as niacytin and unavailable; maize is also low in tryptophan and high in leucine, which inhibits the conversion
—	Sorghum (jowar) diets — high leucine
Secondary — malabsorption	Hartnup disease — defective neutral amino acid transport, so tryptophan is lost
Secondary — diversion	Carcinoid syndrome — tryptophan diverted to serotonin
Secondary — drugs	Isoniazid (antagonises B6), 5-fluorouracil, phenytoin
Secondary — other	Alcoholism, chronic diarrhoea, prolonged parenteral nutrition

Alkali treatment of maize releases the bound niacin — the traditional Mexican preparation of tortillas with lime is why pellagra was rare there despite a maize diet

Largely clinical; the distribution of the rash is characteristic
Urinary N-methylnicotinamide is reduced — the biochemical test
Treatment — nicotinamide 100 mg three times daily, with a high-protein diet and other B vitamins
Nicotinamide is preferred to nicotinic acid because it does not cause flushing
Response is rapid — the mental changes improve within days

Pellagra is a disease of monotonous staple diets, historically in maize and jowar eating regions of India, Africa and the southern United States
Goldberger proved it was nutritional, not infectious, in a series of experiments in the early twentieth century — a landmark in epidemiology
Suspect it in any alcoholic with a photosensitive rash and confusion
Prevention — dietary diversification with pulses and groundnut, both rich in tryptophan

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