Hypophosphatasia refers to a rare metabolic disorder characterised by deficient serum alkaline phosphatase activity. The effects of hypophosphatasia are primarily seen in the skeletal system. The condition has marked variation in clinical expression (see subtypes).
The true incidence is uncertain as it is thought many people may live with mild forms of the disease without being diagnosed. Some authors have estimated its prevalence at 1 in 100,000. It can display either autosomal dominant or recessive inheritance, which complicates genetic counselling.
The underlying genetic abnormality is almost exclusively due to a mutation in the ALPL gene that encodes for tissue non-specific alkaline phosphatase (TNSAP) enzyme. This results in defective bone mineralisation and extracellular accumulation of TNSAP substrates. With over 300 different specific mutations recognised, the severity of the resultant clinical disorder depends on the degree to which TNSAP activity is impaired. The severer the impairment, the earlier the presentation.
Hypophosphatasia can be divided into several groups (at least six types 6,8) according to age at presentation 3,6
- perinatal lethal hypophosphatasia: uniformly lethal 3
- perinatal benign hypophosphatasia: variable severity
- infantile hypophosphatasia: lethal in ~50% of cases 3
- childhood hypophosphatasia
- adult hypophosphatasia: relatively mild
Some of the skeletal features are common across subtypes and include 4:
- generalised (usually irregular) osteoporosis
- generalised (usually irregular) metaphyseal changes
- bowing of the long bones
Complications are primarily those of hypercalcaemia.
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