Hypophosphatasia

Hypophosphatasia (HPP) is a rare hereditary disease in which defective bone mineralization leads to impaired tooth and bone development. The causes are mutations in the ALPL gene, which codes for the non-specific alkaline tissue phosphatase.

The clinical picture is very variable and differs greatly among the five subtypes, which are mainly classified according to the age of onset. The later the disease breaks out, the milder the symptoms are.

The lightest form is characterized by tooth disorders and premature tooth loss. Heavier forms are characterized by skeletal deformities such as a tight chest that can lead to respiratory complications, craniosynostosis with brachycephaly, bony bones, shortened extremities, dwarfism and rachitic metaphyseal changes.

Patients suffer from bone and joint pain (pseudogout) and recurrent fractures. Hypercalcaemia can cause vomiting and kidney problems. Affected persons often show a waddling gait, in children it can lead to failure to thrive.

The most severe forms can lead to death shortly after birth, either prenatally or due to respiratory complications. HPP can be inherited both autosomal recessive and autosomal dominant, men and women are equally affected.