Bone

Hypophosphatasia

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Hypophosphatasia, Odontohypophosphatasia

  • Epidemiology
  1. Severe disease is rare
    1. Prevalance: 1:100,000 to 1:300,000 live births
  2. Adult form (less severe)
    1. Prevalence: 1:3100 to 1:508
  • Pathophysiology
  1. Rare genetic metabolic disorder
    1. Gene defect encoding activity of tissue non-specific Alkaline Phosphatase (TNSALP)
      1. More than 400 mutations identified
      2. Autosomal Recessive or Autosomal Dominant inheritance
    2. TNSALP substrates accumulate
      1. Inorganic pyrophosphate
      2. Pyridoxal-5'-phosphate
  2. Serum and bone Alkaline Phosphatase deficiency
    1. Hypercalcemia
    2. Ethanolamine phosphatemia and phosphaturia
  3. Associated with severe skeletal defects similar to Vitamin D-resistant Rickets
    1. Failed calcification of calvarium
    2. Costochondral junction beading
    3. Rachitic bone changes
  • Types
  1. Current classification
    1. Severe (recessive inheritance)
      1. Perinatal
      2. Infantile Severe
    2. Moderate (Autosomal Dominant or recessive inheritance)
    3. Mild
  2. Historical Classification
    1. Perinatal
    2. Prenatal benign
    3. Infantile
    4. Childhood
    5. Adult
    6. Odontohypophosphatasia
  • Findings
  1. Lung
    1. Dyspnea
    2. Cyanosis
  2. Gastrointestinal
    1. Vomiting
    2. Constipation
  3. Renal
    1. Renal calcinosis
  4. Growth and Development
    1. Fetal demise (in utero)
    2. Failure to Thrive
  5. Dental (Odontohypophosphatasia)
    1. Premature deciduous teeth loss
    2. Early adult teeth loss
  6. Musculoskeletal
    1. Osteomalacia
    2. Skeletal defects
    3. Recurrent, poorly healing Fractures
    4. Movement Disorders and Muscle Weakness
  • Labs
  1. Serum Alkaline Phosphatase
    1. Low for age
  2. Tissue non-specific Alkaline Phosphatase (TNSALP) natural substrate increased levels
    1. Pyridoxal 5'-phosphate
    2. Phosphoethanolamine
  • Imaging
  1. XRay changes
    1. Rickets like bone changes in children
    2. Fractures (old and new)
  • Management
  1. Multidisciplinary team management
  2. Dietary Calcium restriction in children
  3. Targeted enzyme replacement therapy
  • References
  1. Fenn (2021) J Clin Pathol 74(10):635-40 +PMID: 33931563 [PubMed]
  2. Tournis (2021) J Clin Med 10(23):5676 +PMID: 34884378 [PubMed]