Seventeen-year follow-up of hypophosphatasia diagnosed in middle-aged siblings harboring a novel intronic and a rare missense ALPL gene mutation.
Francesco G Conti, Steven Mumm, Giovanna Gentile et al.
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Case in brief
A 17-year follow-up of middle-aged siblings diagnosed with hypophosphatasia revealed painful proximal femoral stress fractures, generalized muscle and bone pain, and tooth loss. Genetic analysis identified compound heterozygosity for a rare missense mutation and a novel intronic change in the ALPL gene. One sister showed significant improvement with asfotase alfa therapy, but deterioration occurred after treatment cessation, highlighting the need for ongoing management.
What made this case unusual
The siblings exhibited a rare combination of ALPL mutations, including a novel intronic mutation predicting a cryptic splice site, which contributed to their clinical presentation.
Diagnostic / clinical pearl
Clinicians should consider hypophosphatasia in patients with unexplained bone pain and fractures, especially when accompanied by dental issues, and investigate potential genetic mutations.
Why it matters
This case emphasizes the necessity of continuous monitoring and treatment adherence in managing hypophosphatasia to prevent clinical deterioration and maintain quality of life.