Safety and efficacy of long term asfotase alfa treatment in childhood hypophosphatasia

被引：0

作者：

Debora Mariarita d’Angelo ^{[1
]}

Federico Lauriola ^{[1
]}

Luisa Silvestrini ^{[1
]}

Luigia Cinque ^{[2
]}

Marco Castori ^{[2
]}

Giulia Di Donato ^{[1
]}

Armando Di Ludovico ^{[1
]}

Saverio La Bella ^{[1
]}

Francesco Chiarelli ^{[1
]}

Cosimo Giannini ^{[1
]}

Luciana Breda ^{[1
]}

机构：

[1] Department of Pediatrics, University of Chieti-Pescara “G. D’Annunzio”, Chieti

[2] Division of Medical Genetics, IRCCS “Casa Sollievo Della Sofferenza”, San Giovanni Rotondo

来源：

Italian Journal of Pediatrics | / 51卷 / 1期

关键词：

Alkaline phosphatase; Asfotase alpha; Genu valgus; Hypophosphatasia; Limping; X-linked hypophosphatasia;

D O I：

10.1186/s13052-025-01883-2

中图分类号：

学科分类号：

摘要：

Background: Hypophosphatasia (HPP) is a rare inherited disorder characterized by a deficiency of tissue-non-specific alkaline phosphatase (TNSALP) due to loss-of-function variants of the ALPL gene. HPP is characterized by an extremely variable age of onset and clinical presentation, largely depending on the type of genetic disruption. Childhood HPP commonly presents with skeletal deformities, bone fragility, precocious tooth loss, muscle weakness and sometimes neurological implications. Laboratory tests usually document low levels of alkaline phosphatase (ALP), and radiologic investigations show peculiar bone abnormalities. Treatment with human recombinant TNSALP (asfotase alpha, Strensiq®), available since 2015, is associated with a sudden improvement and a good safety profile. Case presentation: A previously healthy 15-month-old girl presented with progressive “genu valgus” and sudden limping. The patient was diagnosed with childhood HPP due to the presence of two ALPL variants, never described in compound heterozygosity: a missense variant c.571G > A, p.(Glu191Lys), and a frameshift deletion c.963delG; p.(Lys322Argfs*44), both classified as pathogenetic. The child was promptly treated with asfotase alpha, and good improvement was quickly obtained. Efficacy, safety, and good tolerance persisted after a long-term follow-up of 6 years. Conclusions: Pediatricians should consider HPP in children presenting with a suggestive clinical phenotype. Calcium-phosphorus metabolism, ALP, and vitamin B6 should always be investigated in suspected cases. Moreover, asfotase alfa represents a safe, well-tolerated, and effective drug in children with HPP. © The Author(s) 2025.

引用

共 10 条

[1] Rush E., Brandi M.L., Khan A., Ali D.S., Al-Alwani H., Almonaei K., Et al., Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group, Osteoporos Int, 35, pp. 1-10, (2024)
[2] Martinez-Heredia L., Munoz-Torres M., Sanabria-de la Torre R., Jimenez-Ortas A., Andujar-Vera F., Gonzalez-Cejudo T., Et al., Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene, Front Endocrinol (Lausanne), 14, (2023)
[3] Whyte M.P., Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment, Nat Rev Endocrinol, 12, pp. 233-246, (2016)
[4] Baroncelli G.I., Carlucci G., Freri E., Giuca M.R., Guarnieri V., Navarra G., Et al., The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion, J Endocrinol Invest, (2023)
[5] Richards S., Aziz N., Bale S., Bick D., Das S., Gastier-Foster J., Et al., Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genet Med, 17, pp. 405-424, (2015)
[6] Mornet E., Yvard A., Taillandier A., Fauvert D., Simon-Bouy B., A molecular‐based estimation of the prevalence of hypophosphatasia in the European population, Ann Hum Genet, 75, pp. 439-445, (2011)
[7] Mannes I., Rothenbuhler A., Merzoug V., Di Rocco F., Linglart A., Adamsbaum C., Imaging patterns in pediatric hypophosphatasia, Pediatr Radiol, 52, pp. 998-1006, (2022)
[8] Spentchian M., Merrien Y., Herasse M., Dobbie Z., Glaser D., Holder S.E., Et al., Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene, Hum Mutat, 22, pp. 105-106, (2003)
[9] del Angel G., Reynders J., Negron C., Steinbrecher T., Mornet E., Large-scale in vitro functional testing and novel variant scoring via protein modeling provide insights into alkaline phosphatase activity in hypophosphatasia, Hum Mutat, 41, pp. 1250-1262, (2020)
[10] Whyte M.P., Zhang F., Wenkert D., Mack K.E., Bijanki V.N., Ericson K.L., Et al., Hypophosphatasia: vitamin B6 status of affected children and adults, Bone, 154, (2022)

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