Histologic and ultrastructural studies on the mineralization process in hypophosphatasia.

Chondroosseous tissue from six infants with infantile hypophosphatasia and six control infants were studied by light, transmission, and scanning electron microscopy. Alkaline phosphatase histochemical reaction of the growth plate was studied in two infants and was greatly reduced when compared to two control infants. Hypertrophic chondrocytes were increased in number with persisting cartilage islets in the metaphysis. In five of the six cases studied, chondrocytes and intercartilagenous intercellular chondroid matrix appeared ultrastructurally normal. Matrix vesicle distribution was similar to that of control subjects, but they were associated with few mineral crystals. In two infants, the matrix vesicles were alkaline phosphatase nonreactive. In the calcifying zone of the growth plate and in the newly formed metaphyseal trabecular bone, cartilagenous calcospherites often were small and the orientation of crystals was nonradial when compared to that of control infants. The mineralization of diaphyseal bone appeared normal. It seems that matrix vesicles are present in hypophosphatasia and that the impaired mineralization of cartilage is due primarily to the deficiency of alkaline phosphatase. In spite of the lack of alkaline phosphatase, secondary mineralization of bone which is not mediated by matrix vesicles was normal.

Hypophosphatasia. Review of 24 cases.

Radiographic analysis of 24 cases of hypophosphatasia (H) from 9 Paediatric Centres was performed. 3 cases were of neonatal (lethal), 18 cases of infantile (severe) and 3 cases of late (benign) type. Some of the patients were in reality borderline cases between these groups. In the authors' material all the patients showed radiographic signs of the disease. These were divided into diagnostic, characteristic and suggestive features. All of the patients had in common generalised (usually irregular) osteoporosis, generalised (usually irregular) metaphyseal changes, craniostenosis (13 of 18 infantile cases) or widened cranial sutures and ofter bowing of the long bones. Besides the well know radiographic features of hypophosphatasia some less well known, rare or 'new' ones such as, 1. spurs of the long bones (Bowdler sign), 2. distal femoral central metaphyseal defects and epiphyseal defects, 3. S-like deformities of the tibiae, 4. abnormal shape of the distal phalanges of the fingers, 5. multiple rib fractures and slender bones, 6. wedging of the lower thoracic and upper lumbar vertebrae, 7. partial premature fusion of the epiphyses, 8. nephrocalcinosis, 9. loss of lamina dura around the teeth, 10. variation in radiographic appearances of a pair of siblings with lethal form, and, 11. rapid changes in roentgen appearances. are discussed. In two of our patients (siblings) phosphoethanolamine was undetectable in the urine. The authors doubt if a normal skeletal survey may be present at any stage in any of the three major types of hypophosphatasia.

[Radiological diagnosis (and differential diagnosis) of lethal type (congenital type) of hypophosphatasia (author's transl)]. / Zur Röntgendiagnostik der Hypophosphatasie vom letalen Typ

Diagnosis of Hypophosphatasia can be proved by typical radiological findings. The paper presents a case report of a newborn living only a few hours. Diagnosis according to clinical aspect was "Osteogenesis imperfecta" although a postmortal x-ray-babygram was available but which had not been shown to a radiologist. Anatomical diagnosis with the histological findings was then altered to "Metaphyseal chondrodysplasia, Jansen-type". Finally the diagnosis could be corrected to congenital, lethal type of Hypophosphatasia after the babygram had been shown to a radiologist. The typical radiological features of congenital Hypophosphatasia are described subsequently and differential diagnosis of Congenital Osteochondrodysplasias is discussed. The importance of early or postmortal diagnosis for genetic counselling is stressed as well as a close cooperation between obstetricians and pediatric radiologists. Typical biochemical findings are mentioned.