Hartnup disease
🌞 Hartnup disease is a rare inherited disorder of amino acid transport affecting the kidney and gastrointestinal tract. It leads to tryptophan deficiency, resulting in reduced nicotinamide (vitamin B3) synthesis. This underlies its pellagra-like features such as rash, ataxia, and neuropsychiatric symptoms.
📖 About Hartnup Disease
- Type: Neutral aminoaciduria (defective transport of neutral amino acids like tryptophan, alanine, serine, threonine).
- Inheritance: Autosomal recessive 🧬.
- Typical Presentation: Pellagra-like rash + cerebellar ataxia in childhood or adolescence.
🧪 Aetiology & Pathophysiology
- Gene: Mutations in SLC6A19 (encodes a sodium-dependent neutral amino acid transporter).
- Defect: Impaired absorption in renal tubules & intestinal mucosa → loss of tryptophan.
- Consequence: ↓ Tryptophan → ↓ nicotinamide (niacin, vitamin B3) → NAD/NADP deficiency → pellagra-like symptoms.
- Triggers: Illness, fever, sunlight ☀️, malnutrition, sulfonamide antibiotics, and psychological stress can exacerbate symptoms.
🩺 Clinical Features
- Dermatological: Pellagra-like photosensitive rash, erythema, desquamation in sun-exposed areas.
- Neurological: Cerebellar ataxia (wide-based gait), tremor, dysarthria.
- Psychiatric: Anxiety, depression, irritability, mood swings.
- Cognition: Mostly normal development, though mild intellectual disability may occur.
- Other: Episodes often intermittent, worsening with sunlight or poor diet.
🔬 Investigations
- Urine amino acid chromatography: Neutral aminoaciduria (↑ tryptophan, alanine, serine, threonine).
- Plasma tryptophan: Low levels.
- Newborn screening: Sometimes detects abnormal amino acid patterns.
- Genetic testing: Confirms SLC6A19 mutations.
💊 Management
- Dietary: High-protein, well-balanced diet with adequate niacin intake.
- Vitamin Supplementation: Nicotinamide (vitamin B3) to prevent pellagra-like episodes.
- Avoid Triggers: Minimize excessive sunlight, avoid sulfonamides when possible, and treat intercurrent illness promptly.
- Supportive Care: Psychological support for mood/behavioural symptoms.
⚕️ Clinical Relevance
- Resembles pellagra (dermatitis, diarrhoea, dementia) but due to defective tryptophan transport rather than dietary niacin deficiency.
- Important to distinguish from other causes of ataxia + rash in children (e.g., ataxia telangiectasia, Friedreich’s ataxia, vitamin deficiencies).
- With treatment, prognosis is excellent, but untreated cases risk repeated neurological and dermatological episodes.
