IBMS BoneKEy | Clinical Cases
Asfotase alfa treatment of an African-American infant with perinatal hypophosphatasia and homozygous hemoglobin SC disease
Alaina P Vidmar
Hypophosphatasia (HPP, OMIM #241500) is characterized by defective bone mineralization, associated with decreased activity of the tissue non-specific alkaline phosphatase (TNSALP), due to mutations in the ALPL gene. Asfotase alfa is a bone-targeted recombinant alkaline phosphatase, currently Food and Drug Administration approved for infantile and pediatric onset HPP. We report a 7-month-old African-American girl with prenatal HPP. On day 4 of life, she was started on asfotase alfa. Skeletal survey obtained at 6 weeks of age, revealed improved calcification of all osseous structures. ALPL gene sequencing revealed a novel heterozygous compound c.46_49delAACT/c.360_361 delGG mutation. Tracheostomy tube was placed at 15 weeks of age and she was maintained on long-term ventilator settings until 7 months of age when she died secondary to overwhelming culture-negative sepsis and multi-organ failure. Perinatal HPP is associated with high mortality rate due to respiratory failure, poor ventilation and need for aggressive respiratory management. We report a case of a novel compound heterozygous ALPL gene sequence variant c.46_49delAACT/c.360_361 delGG in an African-American girl with HPP and homozygous HbSC disease who survived up to 7 months of age after early diagnosis and treatment with asfotase alfa, and high-dose supplementation with cholecalciferol and calcium.
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