= autosomal recessive congenital disease with low activity of serum-, bone-, liver-alkaline phosphatase resulting in poor mineralization (= deficient generation of bone crystals)

Prevalence: 1÷100,000

Histo: indistinguishable from rickets

• phosphoethanolamine in urine as precursor of alkaline phosphatase; normal serum calcium + phosphorus

1. GROUP I = neonatal = congenital lethal form
   • marked demineralization of calvarium (“caput membranaceum” = soft skull)
   • lack of calcification of metaphyseal end of long bones
   • streaky irregular spotty margins of calcification
   • cupping of metaphysis
   • angulated shaft fractures with abundant callus formation
   • short poorly ossified ribs
   • poorly ossified vertebrae (especially neural arches)
   • small pelvic bones
   
   OB-US:
   • high incidence of intrauterine fetal demise
   • increased echogenicity of falx (enhanced sound transmission ← poorly mineralized calvarium)
   • poorly mineralized short bowed tubular bones + multiple fractures
   • poorly mineralized spine
   • short poorly ossified ribs
   • polyhydramnios
   
   Prognosis: death within 6 months
2. GROUP II = juvenile severe form
   onset of symptoms within weeks to months
   • moderate / severe dwarfism
   • delayed weight bearing
   • resembles rickets
   • separated cranial sutures; craniostenosis in 2^nd year
   
   Prognosis: 50% mortality
3. GROUP III = adult mild form
   recognized later in childhood / adolescence / adulthood
   • dwarfism
   • clubfoot, genu valgum
   • demineralization of ossification centers (at birth / 3–4 months of age):
   • widened metaphyses
   • wormian bones
   
   Prognosis: excellent; after 1 year no further progression
4. GROUP IV = latent form of heterozygous state
   • normal / borderline levels of alkaline phosphatase
   • patients are small for age
   • disturbance of primary dentition
   • bone fragility + healed fractures
   • enlarged chondral ends of ribs
   • metaphyseal notching of long bones
   • Erlenmeyer flask deformity of femur