[Congenital hypophosphatasia].
Hypophosphatasia represents an inborn enzymatic deficiency characterized by a reduced activity of alkaline phosphatase in serum and tissue and an increased urinary excretion of phosphoethanolamine. 278 cases have been described until the end of 1980. Based on the age of manifestation and the predominant clinical findings the following classification is possible: The prenatal form (49 cases) with caput membranaceum, skeletal deformities and respiratory distress has a mortality of 100%. The early infantile form (94 cases) shows rickets-like osseous anomalies, dystrophy, craniostenosis, nephrocalcinosis, mortality amounting to 40%. Diagnostic features of the infantile-juvenile form (112 cases) are premature loss of deciduous teeth, bone deformities, rickets-like findings, and short stature. Mortality is only 1%. The adult form (23 cases) often remains undiscovered and has a good prognosis. It presents with pseudofractures and pains in the bones as chief symptoms. Heredity is autosomal recessive in all four types of hypophosphatasia. Possibly in the adult form there is an additional autosomal dominant inheritance. Alkaline phosphatase deficiency affects all tissues excepting the intestinal isoenzyme. Urinary excretion of phosphoethanolamine is elevated. Values for calcium and inorganic phosphorus in serum are usually normal or only slightly increased. Marked hypercalcemia is observed in severely diseased patients affected by the early infantile form. In these cases hypercalcemia often leads to nephrocalcinosis and renal insufficiency. Since alkaline phosphatase is equally active as pyrophosphatase, reduced phosphatase activity induces an accumulation of pyrophosphate in serum and its increased excretion in urine. The precise pathogenetic mechanisms of hypophosphatasia are still unknown. Possibly, the accumulation of pyrophosphate implies a disorder of calcification. Postnatal diagnosis is based on clinical findings in association with decreased alkaline phosphatase activity and increased phosphoethanolamine excretion. For the detection of heterozygotes additional biochemical markers should be tested. These include the determination of alkaline phosphatase in leucocytes and cultured skin fibroblasts, the calculation of tubular phosphate reabsorption and the analysis of pyrophosphate and pyrophosphatases. The difficulty in ascertaining the carrier state is that the measurement of a single parameter may give normal results.(ABSTRACT TRUNCATED AT 400 WORDS)
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood / Q000172:deficiency; D002118:Calcium / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D011756:Diphosphates / Q000097:blood; D004983:Ethanolamines / Q000652:urine; D005260:Female; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes / Q000097:blood; D009999:Ossification, Heterotopic / Q000175:diagnosis; D010710:Phosphates / Q000097:blood; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011379:Prognosis; D011755:Pyrophosphatases / Q000172:deficiency
D011756:Diphosphates; D004983:Ethanolamines; D007527:Isoenzymes; D010710:Phosphates; C005448:phosphorylethanolamine; D000469:Alkaline Phosphatase; D011755:Pyrophosphatases; D002118:Calcium
Die kongenitale Hypophosphatasie.