Peer-reviewed article
Adult hypophosphatasia presenting with recurrent acute joint pain.
Hayao Yoshida, Takaaki Murakami, Atsubumi Ogawa, Takashi Sunouchi, Naoko Hidaka et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical case report about a 22-year-old adult diagnosed with hypophosphatasia, a genetic disorder affecting bone metabolism. The patient presented with repeated severe joint pain rather than typical bone symptoms. Genetic testing confirmed compound heterozygous mutations in the ALPL gene. Enzyme replacement therapy with asfotase alfa appeared to resolve the joint pain symptoms during one year of follow-up.
Key points
- Adult hypophosphatasia can present with arthralgia (joint pain) as the only symptom, without typical bone-related manifestations
- Low serum alkaline phosphatase levels with elevated pyrophosphate and pyridoxal-5'-phosphate suggest HPP diagnosis
- Genetic testing revealed compound heterozygous mutations (c.979T>C and c.1559del) in the ALPL gene
- Enzyme replacement therapy with asfotase alfa prevented recurrent joint pain attacks during one-year follow-up
- Parents were identified as carriers of individual pathogenic variants
Limitations
This is a single case report of an adult patient, so findings cannot be generalised to children or to determine the prevalence or long-term outcomes of this presentation. The one-year follow-up period is relatively short for assessing the durability of treatment effects.
Abstract
SUMMARY: Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5'-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. LEARNING POINTS: A diagnosis of adult HPP without bone-related symptoms can be challenging. A reduction in tissue-nonspecific ALP activity leads to an accumulation of pyrophosphate in the joints, which can cause arthralgia. Some cases of adult HPP have arthralgia as the only presenting symptom. At one-year follow-up, enzyme replacement therapy with asfotase alfa might lead to a reduction in arthralgia attacks due to HPP.