Clinical Chemistry - Case Study
https://doi.org/10.1093/clinchem/hvae108
A 33-year-old White female was referred to the endocrine clinic for a decreased serum alkaline phosphatase (ALP) result.
Student Discussion Document (pdf)
Nicole J. Mathewson, Kwaku Baryeh, Joseph W. Rudolf, Vishnu Sundaresh, and Vrajesh Pandya
A 33-year-old White female was referred to the endocrine clinic for a decreased serum alkaline phosphatase (ALP) result. She had been suffering from daily generalized body aches since the age of 15 years. She had not sustained any fractures. A few months before the presentation, she was diagnosed with rapidly progressing advanced periodontal bone loss without the loss of teeth. On review of her laboratory results, serum ALP activities for the past 12 years were all below the reference interval. Notably, her serum vitamin B6 (pyridoxal 5′-phosphate) was increased together with a mildly increased ratio of urine phosphoethanolamine (PEP) to creatinine, raising suspicion for hypophosphatasia (HPP). Genetic testing identified a heterozygous pathogenic variant, c.881A>C (p.Asp294Ala), in the alkaline phosphatase gene (ALPL) confirming a diagnosis of autosomal dominant HPP. Dual-energy X-ray absorptiometry reported normal bone density for age and gender. An X-ray of her ribs did not report rachitic changes. After a normal ophthalmic exam and renal ultrasound, asfotase alfa, a form of enzyme replacement therapy (ERT), was initiated. ERT resulted in an 80% improvement in her musculoskeletal pain with the expected decrease in serum vitamin B6 concentration. However, ALP activities were undetectable on 2 occasions, an unexpected finding in the context of initiating ERT. Hence, the ordering physician contacted the laboratory regarding the inconsistent ALP activity measurements.