TY - JOUR
T1 - Status Epilepticus due to Asfotase Alfa Interruption in Perinatal Severe Hypophosphatasia
AU - Ogawa, Eri
AU - Shimura, Kazuhiro
AU - Yoshihashi, Hiroshi
AU - Miyama, Sahoko
N1 - Funding Information:
The authors are grateful to Drs. Takahiro Mori, MD, Yoshikazu Kitami, MD, Shuhei Fujino, MD, and Hiromi Suzuki, MD, for their constructive discussion of the patient's clinical care. Author contributions: Dr. Ogawa drafted the manuscript. Drs. Ogawa and Shimura treated the patient and revised the manuscript for intellectual content. Dr. Yoshihashi described the discussion on gene mutation in the manuscript. Dr. Miyama treated the patient and critically reviewed the manuscript for important intellectual content. All the authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Conflicts of interest and source of funding statement: The authors declare no conflict of interest or financial disclosures concerning the materials or methods used in this study or the findings specified in this article.
Publisher Copyright:
© 2021
PY - 2022/5
Y1 - 2022/5
N2 - Background: Hypophosphatasia (HPP), an inherited, metabolic disorder caused by loss-of-function mutations in the ALPL gene, affects not only bone and tooth mineralization but also central nervous system (CNS) function, resulting in vitamin B6/pyridoxine-responsive seizures. Asfotase alfa treatment mainly improves the skeletal manifestations of HPP. As of yet, there are no reports demonstrating seizure exacerbation caused by asfotase alfa interruption. Case: The patient was a 2-year and 8-month-old female with clinical and genetic diagnosis of perinatal severe HPP. Genetic analysis of ALPL identified compound heterozygous variants. Asfotase alfa and pyridoxine administration begun on postnatal day 2 restored normal development and suppressed seizures except for simple febrile seizures. From age 2 years when her asfotase alfa injections became irregular, she began experiencing seizure exacerbation, including status epilepticus, leading to acute encephalopathy and severe sequelae. The seizure exacerbations always coincided with low alkaline phosphatase (ALP) activity caused by the interruption of asfotase alfa administration. Discussion: The clinical course of the present case demonstrated the effect of asfotase alfa on CNS symptoms and a clear correlation between low serum ALP activity and seizure exacerbation. Serum ALP activity measurements were useful as a therapeutic marker in the present case. Furthermore, the risk of seizure exacerbation in the patient could have been predicted, given the genotype-phenotype correlation related to the ALPL gene in the Japanese population. Conclusion: Regular asfotase alfa injections are needed to prevent seizure exacerbation in patients with HPP. Educating patients and their family about the need for regular asfotase alfa treatment is crucial to preventing disease exacerbation.
AB - Background: Hypophosphatasia (HPP), an inherited, metabolic disorder caused by loss-of-function mutations in the ALPL gene, affects not only bone and tooth mineralization but also central nervous system (CNS) function, resulting in vitamin B6/pyridoxine-responsive seizures. Asfotase alfa treatment mainly improves the skeletal manifestations of HPP. As of yet, there are no reports demonstrating seizure exacerbation caused by asfotase alfa interruption. Case: The patient was a 2-year and 8-month-old female with clinical and genetic diagnosis of perinatal severe HPP. Genetic analysis of ALPL identified compound heterozygous variants. Asfotase alfa and pyridoxine administration begun on postnatal day 2 restored normal development and suppressed seizures except for simple febrile seizures. From age 2 years when her asfotase alfa injections became irregular, she began experiencing seizure exacerbation, including status epilepticus, leading to acute encephalopathy and severe sequelae. The seizure exacerbations always coincided with low alkaline phosphatase (ALP) activity caused by the interruption of asfotase alfa administration. Discussion: The clinical course of the present case demonstrated the effect of asfotase alfa on CNS symptoms and a clear correlation between low serum ALP activity and seizure exacerbation. Serum ALP activity measurements were useful as a therapeutic marker in the present case. Furthermore, the risk of seizure exacerbation in the patient could have been predicted, given the genotype-phenotype correlation related to the ALPL gene in the Japanese population. Conclusion: Regular asfotase alfa injections are needed to prevent seizure exacerbation in patients with HPP. Educating patients and their family about the need for regular asfotase alfa treatment is crucial to preventing disease exacerbation.
KW - Appropriate serum ALP activity
KW - Asfotase alfa interruption
KW - Genotype-phenotype correlation
KW - Perinatal severe hypophosphatasia
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U2 - 10.1016/j.pediatrneurol.2021.12.009
DO - 10.1016/j.pediatrneurol.2021.12.009
M3 - Article
C2 - 35303588
AN - SCOPUS:85126290880
SN - 0887-8994
VL - 130
SP - 4
EP - 6
JO - Pediatric Neurology
JF - Pediatric Neurology
ER -