Hypophosphatasia (HPP) is a rare disease caused by changes in the ALPL gene – these changes are also known as “variants”. This study analyzed 685 patients from the Global HPP Registry to compare disease burden in patients with 1 variant versus those with 2 or more variants in the ALPL gene. No differences were reported in pain, disability, or quality of life between the two groups of patients. These findings demonstrate that patients with HPP have a high disease burden regardless of the number of variants in their ALPL gene. (By Dr. Priya S Kishnani, https://jmg.bmj.com/content/62/4/249 )