Low Alkaline Phosphatase - Hypophosphatasia Is Low Alkaline Phosphatase Of Clinical Importance? ALP enzyme- Discovered in 1923 Low ALP: Hypophosphatasia recognized in 1948 by Rathbun ALP synthesized in: liver, bone, placenta and proximal convoluted tubule of the kidney. Most cases diagnosed during childhood and adolescence. Adult form: Less severe • softening of bones- osteomalacia • recurrent fractures of feet, thigh bones -> chronic pain • loss of secondary teeth prematurely • risk of joint pain and inflammation • nephrocalcinosis • CPPD • severe mobility/functional impairment • Neuropathy ALP is critical for metabolizing 3 substrates: • Pyridoxal 5' phosphate: Impairs Vit. B6 transport across the plasma membrane into the CNS • Inorganic pyrophosphate: Inhibitor of bone mineralization • Phosphoethanolamine Low ALP in adult population: also due to: • Malnutrition • Wilson's disease • hypothyroidism • Zinc deficiency • Vitamin C deficiency • Low phosphorus level • Pernicious anemia/B12 deficiency • blood collection with EDTA Pathophysiology: • Activators of ALP → ↓ALP • Hypophosphatasia, ↓ALP → Low ALP -> PPi and Calcium accumulate → PPi (inorganic pyrophosphate) blocks hydroxyapatite crystal formation causing poor bone mineralization Symptoms of Low Alkaline Phosphatase: • Respiratory: - respiratory failure • Neurologic: - Increased intracranial pressure - Elevated Vit B6- neuropathy • Renal: - Renal failure - Nephrocalcinosis - Nephrolithiasis • Metabolic: - Hyperuricemia - Hyperlipidemia - Hypercalcemia • Skeletal: - Bone pain - Frequent fractures • Dental: - Premature loss of teeth • Muscular/Rheum: - Hypotonia - Pain (muscle/joint) - Waddling gait - Difficulty walking Diagnosis of Low Alkaline Phosphatase: • Other causes of low ALP eliminated • Elevation of serum Pyridoxal 5' phosphate &/or • Elevation of urinary PEA #Low #Alkaline #Phosphatase #ALP #Hyophosphatasia #hepatology #diagnosis
