Hypophosphatasia congenita letalis

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Hypophosphatasia is a rare genetic disorder characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase.
• This enzymatic defect leads to impaired bone mineralization, causing skeletal abnormalities.
• Elevated levels of specific substrates, such as phosphoethanolamine, are hallmarks of the condition.

Purpose of the Study:

• To report an extremely severe case of infantile hypophosphatasia.
• To detail the clinical, biochemical, and radiological findings in a patient with this rare disorder.
• To discuss the differential diagnosis and prenatal diagnostic approaches for hypophosphatasia.

Main Methods:

• Clinical case presentation.
• Biochemical analysis of serum and urine for alkaline phosphatase activity and substrate levels (phosphoethanolamine, proline).
• Radiographic skeletal surveys.

Main Results:

• The patient presented with severe skeletal hypomineralization, including absence of the cranial vault and shortened, thickened extremities.
• Serum alkaline phosphatase levels were extremely low.
• Markedly increased urinary and serum levels of phosphoethanolamine and proline were observed.

Conclusions:

• This case exemplifies the extreme end of the hypophosphatasia spectrum.
• Early and accurate diagnosis, including prenatal detection, is crucial for management.
• Understanding the biochemical and clinical spectrum aids in managing patients with this severe disorder.