II. Epidemiology
- Severe disease is rare
- Prevalance: 1:100,000 to 1:300,000 live births
- Adult form (less severe)
- Prevalence: 1:3100 to 1:508
III. Pathophysiology
- Rare genetic metabolic disorder
- Gene defect encoding activity of tissue non-specific Alkaline Phosphatase (TNSALP)
- More than 400 mutations identified
- Autosomal Recessive or Autosomal Dominant inheritance
- TNSALP substrates accumulate
- Inorganic pyrophosphate
- Pyridoxal-5'-phosphate
- Gene defect encoding activity of tissue non-specific Alkaline Phosphatase (TNSALP)
- Serum and bone Alkaline Phosphatase deficiency
- Hypercalcemia
- Ethanolamine phosphatemia and phosphaturia
- Associated with severe skeletal defects similar to Vitamin D-resistant Rickets
- Failed calcification of calvarium
- Costochondral junction beading
- Rachitic bone changes
IV. Types
- Current classification
- Severe (recessive inheritance)
- Perinatal
- Infantile Severe
- Moderate (Autosomal Dominant or recessive inheritance)
- Mild
- Severe (recessive inheritance)
- Historical Classification
- Perinatal
- Prenatal benign
- Infantile
- Childhood
- Adult
- Odontohypophosphatasia
V. Findings
- Lung
- Gastrointestinal
- Renal
- Renal calcinosis
- Growth and Development
- Fetal demise (in utero)
- Failure to Thrive
- Dental (Odontohypophosphatasia)
- Premature deciduous teeth loss
- Early adult teeth loss
- Musculoskeletal
- Osteomalacia
- Skeletal defects
- Recurrent, poorly healing Fractures
- Movement Disorders and Muscle Weakness
VI. Labs
-
Serum Alkaline Phosphatase
- Low for age
- Tissue non-specific Alkaline Phosphatase (TNSALP) natural substrate increased levels
- Pyridoxal 5'-phosphate
- Phosphoethanolamine
VIII. Management
- Multidisciplinary team management
- Dietary Calcium restriction in children
- Targeted enzyme replacement therapy