Intracranial hypertension in a boy with infantile hypophosphatasia requiring shunt installation

Infantile hypophosphatasia is a rare autosomal recessive disorder of bone metabolism. It is caused by mutations in the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP) and is primarily characterized by hypercalcemia, widespread demineralization, rickets, nephrocalcinosis and premature loss of decidual teeth. In a few cases intracranial hypertension was described as an additional symptom mostly resulting from premature fusion of cranial sutures, but in one patient the intracanial hypertension was classified as pseudotumor cerebri and treated successfully with steroids.

We report a male infant with hypophosphatasia diagnosed by DNA sequencing of the TNSALP gene at the age of 4 months. He presented with severe hypercalcemia, failure to thrive and nephrocalcinosis. The serum alkaline phosphatase activity was low. Hypercalcemia needed extensive pharmacotherapy with diuretics, calcitonin and steroids. At the first presentation of the infant a bulging fontanel was noticed. It disappeared after 3 weeks of therapy but developed again one month later although calcium levels were normal. At this time additionally pathological cerebral doppler flows were recorded. Cranial sutures were widely open. Cranial MRI showed normal internal and slightly dilated external CSF spaces in the frontal regions, no signs of venous outflow obstruction were detected. CSF opening pressure was notably high at 400 mmH_2O. In spite of treatment with repeated lumbar punctures, acetazolamide, non-steroidal drugs and steroids no lasting effect was achieved. Finally a ventriculoperitoneal shunt was installed resulting in a normal intracranial pressure. Subsequently the boy's motor development improved markedly.

The relevance of different mechanisms (hypercalcemia, metabolic inflammation, functionally closed sutures) for the pathogenesis of intracranial hypertension in this boy is discussed.