Fetal congenital lethal hypophosphatasia: Histochemical absence of alkaline phosphatase activity in endothelial cells of intramuscular capillaries

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP). Pediatricians encounter a perinatal, an infantile and a childhood form of the disease, but in all cases the predominant feature is defective mineralization. Clinical severity and classification generally reflect the age at which rickets develops. Patients with perinatal hypophosphatasia are stillborn or live only a few days. Infantile hypophosphatasia (onset within the first six months) causes dramatically reduced skeletal mineralization and systemic symptoms such as recurrent pneumonia, vomiting, convulsions and muscle weakness. Childhood hypophosphatasia results in rickets and premature loss of teeth. In children with an especially mild form of the disease, the mineralization defect is restricted to the teeth (odontohypophosphatasia). Study of the disease is also contributing significantly to knowledge of the biology of human TNSALP. Skin fibroblasts derived from patients provide an in vitro system for studies of hypophosphatasia.

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Hypophosphatasia and the Extracellular Metabolism of Inorganic Pyrophosphate: Clinical and Laboratory Aspects: Part I

Caswell¹,

Whyte²,

Russell³

1991

Critical Reviews in Clinical Laboratory Sciences

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Hypophosphatasia is a rare inherited disorder in which the activity of the bone/liver/kidney or tissue nonspecific form of alkaline phosphatase (ALP) is reduced. The clinical expression of the disease is highly variable, but in early life the severity tends to reflect the age of onset. Accordingly, the disease is often classified into perinatal, infantile, and childhood forms. Hypophosphatasia also occurs in adults. Some exhibit symptoms in adulthood for the first time, but others have a history of the disease in early life with an intervening symptom-free period. Defective mineralization of bones and teeth is the predominant clinical feature of all forms of the disease. Biochemically, the reduction in ALP activity is associated with alterations in the extracellular metabolism of various phosphorylated compounds, including inorganic pyrophosphate (PPi), phosphoethanolamine, and pyridoxal 5'-phosphate. Of these, PPi may have an especially important role in the development of the mineralization defect. Accordingly, the extracellular metabolism of PPi and its possible role in the regulation of mineralization will be discussed.

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Fetal congenital lethal hypophosphatasia: Histochemical absence of alkaline phosphatase activity in endothelial cells of intramuscular capillaries

Cited by 4 publications

References 4 publications

Muscle Biopsy

Muscle Biopsy

Hypophosphatasia: Pediatric Forms

Hypophosphatasia and the Extracellular Metabolism of Inorganic Pyrophosphate: Clinical and Laboratory Aspects: Part I

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