Unsolved diagnostic issues of hypophosphatasia: Expert Council
DOI: 10.32364/2587-6821-2021-5-9-605-614
E.Yu. Zakharova1, T.V. Varlamova2, S.V. Voronin3, N.Yu. Vlasenko4, E.M. Kochegurova5,6, A.M. Mambetova7, N.L. Pechatnikova8, I.B. Sosnina9, O.V. Udalova10, E.B. Khramova11
1Research Center for Medical Genetics, Moscow, Russian Federation
2Petrozavodsk State Univerity, Petrozavodsk, Russian Federation
3Regional Clinical Center of Specialized Medical Care, Vladivostok, Russian Federation
4Omsk State Medical University, Omsk, Russian Federation
5 Tver State Medical University, Tver, Russian Federation
6E.M. Bakunina Regional Clinical Perinatal Center, Tver, Russian Federation
7Kh.M. Berbekov Kabardian-Balkar State University, Nalchik, Russian Federation
8Morozov Children’s City Clinical Hospital, Moscow Russian Federation
9Consultative Diagnostic Center for Children, St. Petersburg, Russian Federation
10Privolzhsk Research Medical University, Nizhniy Novgorod, Russian Federation
11Tyumen State Medical University, Tyumen, Russian Federation
Hypophosphatasia (HPP) is a rare hereditary metabolic disease resulting from the loss-of-function mutation in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (ALP). Clinical presentations are polymorphic and manifest themselves differently depending on the age of disease onset and severity. The occurrence of mild disease, including adult HPP, is challenging to assess due to the high heterogeneity of clinical signs and a lower diagnosis rate. Doctors’ awareness of HPP is the fundamental factor affecting its detection rate. This paper reviews the conclusions of the Expert Council on HPP diagnosis and potentialities to improve diagnosis. Ten experts from various Russian regions participated in panel sessions. Each member shared the experience and established practice on the diagnosis of orphan diseases in his/her region and gave suggestions to optimize the diagnostic approach to HPP. The result was the development of a management algorithm and routing of patients from identifying symptoms to decision making on prescribing enzyme-replacement therapy and subsequent follow-up at every level of medical care.
Keywords: hypophosphatasia, alkaline phosphatase, orphan diseases, ALPL, enzyme-replacement therapy, routing.
For citation: Zakharova E.Yu., Varlamova T.V., Voronin S.V. et al. Unsolved diagnostic issues of hypophosphatasia: Expert Council. Russian Medical Inquiry. 2021;5(9):605–614 (in Russ.). DOI: 10.32364/2587-6821-2021-5-9-605-614.
About the authors:
Ekaterina Yu. Zakharova — Dr. Sc. (Med.)., Head of the Laboratory of Hereditary Metabolic Disorders and Selective Screening, Research Center for Medical Genetics; 1, Moskvorechye str., Moscow, 115522, Russian Federation; ORCID iD 0000-0002-5020-1180.
Tat’yana V. Varlamova — C. Sc. (Med.), associate professor of the Department of Pediatrics and Children’s Surgery, Petrozavodsk State Univerity; 33, Lenin av., Petrozavodsk, 185910, Russian Federation; ORCID iD 0000-0001-5617-8893.
Sergey V. Voronin — C. Sc. (Med.), Head of the Regional Medical Genetic Consultation, Regional Clinical Center of Specialized Medical Care; 30/37, Uborevich str., Vladivostok, 690091, Russian Federation; ORCID iD 0000-0002-9918-9565.
Natal’ya Yu. Vlasenko — C. Sc. (Med.), associate professor of the Department of Hospital Pediatrics with the Course of Additional Professional Education, Omsk State Medical University; 12, Lenin str., Omsk, 644099, Russian Federation; ORCID iD 0000-0001-5669-1718.
Elena M. Kochegurova — C. Sc. (Med.), associate professor of the Department of Polyclinic Pediatrics and Neonatology, Tver State Medical University; 4, Sovetskaya str., Tver, 170100, Russian Federation; Head of the Medical Genetic
Consultation, E.M. Bakunina Regional Clinical Perinatal
Center; 115 build. 3, Peterburgskoe road, Tver, 170036, Russian Federation; ORCID iD 0000-0002-8011-589X.
Aneta M. Mambetova — Dr. Sc. (Med.), professor of the Department of General Medical Training and Medical Rehabilitation, Kh.M. Berbekov Kabardian-Balkar State University; 173, Chernyshevskiy str., Nalchik, 360004, Russian Federation; ORCID iD 0000-0003-0378-0754.
Natal’ya L. Pechatnikova — C. Sc. (Med.), Head of Genetic Service, Morozov Children’s City Clinical Hospital; 1/9, 4th Dobryninskiy pass., Moscow, 119049, Russian Federation; ORCID iD 0000-0002-2445-132X.
Irina B. Sosnina — Deputy Head Doctor for Medical Work, Consultative Diagnostic Center for Children; 36 build. 2, Oleko Dundich str., St. Petersburg, 192289, Russian Federation; ORCID iD 0000-0002-0077-9435.
Olga V. Udalova — C. Sc. (Med.), geneticist of the Center of Medical Genetics, Privolzhsk Research Medical University; 10/1, Minin and Pozharskiy sq., Nizhniy Novgorod, 603005, Russian Federation; ORCID iD 0000-0002-8678-4349.
Elena B. Khramova — Dr. Sc. (Med.), Head of the Department of Children’s Diseases of the Pediatric Faculty, Tyumen State Medical University; 54, Odesskaya str., Tyumen, 625023, Russian Federation; ORCID iD 0000-0001-8968-3925.
Contact information: Irina B. Sosnina, e-mail: sosnina_kdcd@mail.ru.
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 17.08.2021.
Revised 09.09.2021.
Accepted 04.10.2021.
2. Michigami T., Ohata Y., Fujiwara M. et al. Clinical practice guidelines for hypophosphatasia. Clin Pediatr Endocrinol. 2020;29(1):9–24. DOI: 10.1297/cpe.29.9.
3. Fraser D. Hypophosphatasia. Am J Med. 1957;22(5):730–746. DOI: 10.1016/0002-9343(57)90124-9.
4. Mornet E., Yvard A., Taillandier A. et al. A Molecular-Based Estimation of the Prevalence of Hypophosphatasia in the European Population. Ann Hum Genet. 2011;75(3):439–445. DOI: 10.1111/j.1469-1809.2011.00642.x.
5. Högler et al. Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC Musculoskeletal Disorders. 2019;20:80.
6. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(Suppl 2):380–388.
7. Ivanov V.P., Satanin L.A., Kim A.V. and other. Neurological and neurosurgical aspects of hypophosphatasia. Pediatric Pharmacology. 2018;15(3):249–254 (in Russ.). DOI: 10.15690 / pf.v15i3.1905.
8. Sosnina I.B., Sukchev M.B., Ivashikina T.M. et al. Experience of retrospective diagnosis of hypophosphatasia in children. RMJ. 2016;26:1778–1781 (in Russ.).
9. Saraff V., Narayanan V.K., Lawson A.J. et al. A diagnostic algorithm for children with low alkaline phosphatase activities: Lessons learned from laboratory screening for hypophosphatasia. J Pediatr. 2016;172:181–186.e1. DOI: 10.1016/j.jpeds.2016.01.045.
10. Baranov A.A., Namazova-Baranova L.S., Savostyanov K.V. et al. Clinical guidelines for the diagnosis and treatment of hypophosphatasia in children. Pediatric Pharmacology. 2016; 13(6): 539–543 (in Russ.).
11. Whyte M.P. Hypophosphatasia. Pediatric bone. Academic Press. 2012;771–794.
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