Allgrove Syndrome (Triple A Syndrome)
Allgrove Syndrome (Triple A Syndrome)
Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of:
- Achalasia
- Alacrima (absence of tears)
- Adrenal insufficiency due to ACTH resistance
First described in 1978 by Allgrove et al., this condition typically presents in the first decade of life.
Key Clinical Manifestations
Cardinal Features:
- Alacrima (100% cases)
- Usually present from birth
- Causes chronic conjunctival irritation
- Often the earliest manifestation
- Achalasia (75% cases)
- Dysphagia
- Regurgitation
- Failure to thrive
- Chronic cough
- Adrenal Insufficiency (85% cases)
- Hypoglycemia
- Hypotension
- Fatigue
- Hyperpigmentation
Associated Features:
- Neurological Manifestations
- Progressive peripheral, central, and autonomic neuropathy
- Muscle weakness
- Mental retardation in some cases
- Parkinsonian features
- Dysarthria
- Dermatological Features
- Palmoplantar hyperkeratosis
- Short stature
- Osteoporosis
Diagnostic Approach
Clinical Assessment:
- Detailed family history
- Physical examination focusing on cardinal features
- Neurological examination
- Growth and development assessment
Laboratory Investigations:
- Endocrine Evaluation:
- Serum cortisol (baseline and ACTH-stimulated)
- Plasma ACTH levels
- Serum electrolytes
- Plasma renin activity
- Ophthalmologic Testing:
- Schirmer test
- Slit lamp examination
- Gastrointestinal Studies:
- Barium swallow
- Esophageal manometry
- Upper GI endoscopy
Genetic Testing:
- AAAS gene sequencing
- Mutation analysis
- Genetic counseling
Treatment Strategies
Multidisciplinary Approach:
- Endocrine Management:
- Glucocorticoid replacement (Hydrocortisone)
- Mineralocorticoid replacement if needed
- Stress dose steroids during illness
- Regular monitoring of replacement therapy
- Ophthalmologic Care:
- Artificial tears
- Lubricating eye drops
- Regular ophthalmologic follow-up
- Gastrointestinal Treatment:
- Pneumatic dilatation for achalasia
- Heller myotomy in selected cases
- Nutritional support
- Neurological Support:
- Physical therapy
- Occupational therapy
- Speech therapy if needed
Emergency Management:
- Adrenal crisis protocol
- Emergency steroid card
- Patient/family education about crisis management
Genetics and Pathophysiology
Genetic Basis:
- Gene: AAAS gene on chromosome 12q13
- Protein: ALADIN (ALacrima Achalasia aDrenal Insufficiency Neurologic disorder)
- Inheritance: Autosomal recessive
Pathophysiology:
- Nuclear Pore Complex:
- ALADIN protein is a component of nuclear pore complexes
- Affects nucleocytoplasmic transport
- Impairs DNA repair and redox homeostasis
- Tissue Effects:
- Neurodegeneration of autonomic neurons
- Progressive loss of adrenal function
- Impaired development of lacrimal glands
