Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children
Abstract Background Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severit...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-020-01500-x |
| _version_ | 1818326341244682240 |
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| author | Marius Vogt Hermann Girschick Tilmann Schweitzer Clemens Benoit Annette Holl-Wieden Lothar Seefried Franz Jakob Christine Hofmann |
| author_facet | Marius Vogt Hermann Girschick Tilmann Schweitzer Clemens Benoit Annette Holl-Wieden Lothar Seefried Franz Jakob Christine Hofmann |
| author_sort | Marius Vogt |
| collection | DOAJ |
| description | Abstract Background Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severity. HPP affects patients of all ages. In children HPP-related musculoskeletal symptoms may mimic rheumatologic conditions and diagnosis is often difficult and delayed. To improve the understanding of HPP in children and in order to shorten the diagnostic time span in the future we studied the natural history of the disease in our large cohort of pediatric patients. This single centre retrospective chart review included longitudinal data from 50 patients with HPP diagnosed and followed at the University Children’s Hospital Wuerzburg, Germany over the last 25 years. Results The cohort comprises 4 (8%) perinatal, 17 (34%) infantile and 29 (58%) childhood onset HPP patients. Two patients were deceased at the time of data collection. Diagnosis was based on available characteristic clinical symptoms (in 88%), low alkaline phosphatase (AP) activity (in 96%), accumulating substrates of AP (in 58%) and X-ray findings (in 48%). Genetic analysis was performed in 48 patients (31 compound heterozygous, 15 heterozygous, 2 homozygous mutations per patient), allowing investigations on genotype-phenotype correlations. Based on anamnestic data, median age at first clinical symptoms was 3.5 months (min. 0, max. 107), while median time to diagnosis was 13 months (min. 0, max. 103). Common symptoms included: impairment of motor skills (78%), impairment of mineralization (72%), premature loss of teeth (64%), musculoskeletal pain and craniosynostosis (each 64%) and failure to thrive (62%). Up to now 20 patients started medical treatment with Asfotase alfa. Conclusions Reported findings support the clinical perception of HPP being a chronic multi-systemic disease with often delayed diagnosis. Our natural history information provides detailed insights into the prevalence of different symptoms, which can help to improve and shorten diagnostics and thereby lead to an optimised medical care, especially with promising therapeutic options such as enzyme-replacement-therapy with Asfotase alfa in mind. |
| first_indexed | 2024-12-13T11:58:50Z |
| format | Article |
| id | doaj.art-4e46608f0c36461cb5ae8368910ee29b |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-13T11:58:50Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-4e46608f0c36461cb5ae8368910ee29b2022-12-21T23:47:09ZengBMCOrphanet Journal of Rare Diseases1750-11722020-08-0115111010.1186/s13023-020-01500-xPediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 childrenMarius Vogt0Hermann Girschick1Tilmann Schweitzer2Clemens Benoit3Annette Holl-Wieden4Lothar Seefried5Franz Jakob6Christine Hofmann7Pediatric Rheumatology and Osteology, University Children’s Hospital WuerzburgChildren’s Hospital, Vivantes Hospital im FriedrichshainDepartment of Neurosurgery, Section of Pediatric Neurosurgery, University Hospital of WürzburgInstitute of Radiology, Division of Pediatric Radiology, University Hospital of WürzburgPediatric Rheumatology and Osteology, University Children’s Hospital WuerzburgBernhard-Heine-Center for Locomotion Research, Orthopedic Department, University of WuerzburgBernhard-Heine-Center for Locomotion Research, Orthopedic Department, University of WuerzburgPediatric Rheumatology and Osteology, University Children’s Hospital WuerzburgAbstract Background Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severity. HPP affects patients of all ages. In children HPP-related musculoskeletal symptoms may mimic rheumatologic conditions and diagnosis is often difficult and delayed. To improve the understanding of HPP in children and in order to shorten the diagnostic time span in the future we studied the natural history of the disease in our large cohort of pediatric patients. This single centre retrospective chart review included longitudinal data from 50 patients with HPP diagnosed and followed at the University Children’s Hospital Wuerzburg, Germany over the last 25 years. Results The cohort comprises 4 (8%) perinatal, 17 (34%) infantile and 29 (58%) childhood onset HPP patients. Two patients were deceased at the time of data collection. Diagnosis was based on available characteristic clinical symptoms (in 88%), low alkaline phosphatase (AP) activity (in 96%), accumulating substrates of AP (in 58%) and X-ray findings (in 48%). Genetic analysis was performed in 48 patients (31 compound heterozygous, 15 heterozygous, 2 homozygous mutations per patient), allowing investigations on genotype-phenotype correlations. Based on anamnestic data, median age at first clinical symptoms was 3.5 months (min. 0, max. 107), while median time to diagnosis was 13 months (min. 0, max. 103). Common symptoms included: impairment of motor skills (78%), impairment of mineralization (72%), premature loss of teeth (64%), musculoskeletal pain and craniosynostosis (each 64%) and failure to thrive (62%). Up to now 20 patients started medical treatment with Asfotase alfa. Conclusions Reported findings support the clinical perception of HPP being a chronic multi-systemic disease with often delayed diagnosis. Our natural history information provides detailed insights into the prevalence of different symptoms, which can help to improve and shorten diagnostics and thereby lead to an optimised medical care, especially with promising therapeutic options such as enzyme-replacement-therapy with Asfotase alfa in mind.http://link.springer.com/article/10.1186/s13023-020-01500-xHypophosphatasiaAlkaline phosphataseAsfotase alfaRare bone diseaseOsteomalaciaRickets |
| spellingShingle | Marius Vogt Hermann Girschick Tilmann Schweitzer Clemens Benoit Annette Holl-Wieden Lothar Seefried Franz Jakob Christine Hofmann Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children Orphanet Journal of Rare Diseases Hypophosphatasia Alkaline phosphatase Asfotase alfa Rare bone disease Osteomalacia Rickets |
| title | Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children |
| title_full | Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children |
| title_fullStr | Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children |
| title_full_unstemmed | Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children |
| title_short | Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children |
| title_sort | pediatric hypophosphatasia lessons learned from a retrospective single center chart review of 50 children |
| topic | Hypophosphatasia Alkaline phosphatase Asfotase alfa Rare bone disease Osteomalacia Rickets |
| url | http://link.springer.com/article/10.1186/s13023-020-01500-x |
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