Endocrine Abstracts

Hypophosphatasia (HP) is a rare inborn error of metabolism resulting from inactivating mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Deficiency of alkaline phosphatase (ALK) activity leads to severe rickets. The perinatal form presents with extreme skeletal hypomineralisation at birth, and was a fatal condition until recently. We describe an 11-month-old infant who is one of the few surviving cases of a preterm infant with the perinatal form (homozygous mutation in TNSALP c.1336G>A) of HP. She has been treated with the recombinant TNSALP (Asfotase alfa) provided on a compassionate basis by Alexion (352 Knotter, CT 06410, United States).

A female infant was born preterm at 34 weeks of gestational age to consanguineous parents of Pakistani descent and required ventilatory support from birth for respiratory insufficiency. She was noted to have short limbs and hypotonia. Radiographs revealed severe skeletal hypomineralisation with features of rickets. Her serum ALK was low however, urinary phosphoethanolamine, serum calcium and serum inorganic pyrophosphatase (iPP) were elevated as expected in patients with HP.

Treatment with Asfotase alfa was commenced at 4 weeks of age. Infant remains on ventilatory support however, treatment has resulted in dramatic improvement in growth and mineralisation of bones, healing of rickets, normalisation of serum calcium and serum iPP, improved developmental milestones and pulmonary function.

Management of this infant has brought about unique challenges which have not been previously reported in medical literature. The dose of Asfotase alfa has been increased steadily (6 mg/kg per dose, three times a week) beyond the usual dose (2 mg/kg per dose) to allow adequate mineralisation of bones and normalisation of serum calcium concentration. Combination of lung disease of prematurity and respiratory comprise from HP has required on going ventilatory support. Nevertheless she is making good developmental progress and plans are underway to discharge her on home ventilatory support.