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Methylmalonic and Propionic Acidemias in the Expanded Newborn Screening Program in the Russian Federation: Evaluation of Diagnostic Performance and Algorithm Optimization

https://doi.org/10.25557/2073-7998.2025.10.16-39

Abstract

Methylmalonic Aciduria (MMA) and propionic aciduria (PA) are rare autosomal recessive disorders of organic acid metabolism. Early diagnosis of these conditions is crucial for the timely initiation of therapy and improved prognosis. Since 2023, the Russian Federation has implemented an expanded newborn screening (NBS) program that includes MMA and PA. Between 2023 and 2024, a total of 2,466,615 newborns were screened. Primary screening using tandem mass spectrometry identified 7,297 neonates at risk for MMA or PA. Confirmatory molecular genetic testing revealed pathogenic or likely pathogenic variants in 28 patients. Of these, 26 newborns were diagnosed with MMA, and 2 newborns were diagnosed with PA. This study established, for the first time, the incidence of MMA and PA in the Russian Federation. The estimated incidence of MMA was 1 in 95,000 newborns (95% CI: 1 in 69,000–1 in 131,000), while the incidence of PA was 1 in 1,234,000 (95% CI: 1 in 409,000–1 in 3,730,000). The positive predictive value (PPV) of the initial screening for MMA and PA was 0.38%. In 38% of MMA patients, the disease manifested during the neonatal period as a metabolic crisis. Previously unreported pathogenic variants were identified in the MMUT, MMAA, MMACHC, and PCCB genes. The implementation of NBS in the Russian Federation has significantly enhanced the early detection of MMA, enabling timely therapeutic intervention. In contrast, the detection rate of PA was lower than expected compared to selective screening data, highlighting the need to optimize primary screening algorithms and confirmatory diagnostic procedures for this disorder. The study also included analysis of the sensitivity and specificity of additional biochemical markers. An optimized confirmatory diagnostic algorithm was proposed to enhance the efficacy of neonatal screening.

About the Authors

P. V. Baranova
Research Centre for Medical Genetics
Russian Federation

1, Moskvorechye st., Moscow, 115522


M. V. Vasileva
Research Centre for Medical Genetics
Russian Federation

1, Moskvorechye st., Moscow, 115522


N. V. Bakin
Research Centre for Medical Genetics
Russian Federation

1, Moskvorechye st., Moscow, 115522


N. V. Moryakova
Research Cent1, Moskvorechye st., Moscow, 115522re for Medical Genetics
Russian Federation


Kh. F. Aksyanova
Nizhny Novgorod Regional Children’s Clinical Hospital
Russian Federation

211, Vaneeva st., Nizhny Novgorod, 603005


A. N. Kolchina
Nizhny Novgorod Regional Children’s Clinical Hospital
Russian Federation

211, Vaneeva st., Nizhny Novgorod, 603005


T. A. Astakhova
Scientific Centre for Family Health and Human Reproduction Problems
Russian Federation

16, Timiryazev st., Irkutsk, 664003


T. A. Bairova
Scientific Centre for Family Health and Human Reproduction Problems
Russian Federation

16, Timiryazev st., Irkutsk, 664003


G. V. Buyanova
Chelyabinsk Regional Children’s Clinical Hospital
Russian Federation

42a, Blyukher st., Chelyabinsk, 454087


A. I. Pobedinskaya
Chelyabinsk Regional Children’s Clinical Hospital
Russian Federation

42a, Blyukher st., Chelyabinsk, 454087


Z. I. Vafina
Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
Russian Federation

138, Orenburgsky trakt, Kazan, 420064


A. I. Gamzatova
Republican Perinatal Center named after. Omarova S.-M.A.
Russian Federation

2, Magomedov st., Makhachkala, 367027


M. V. Gorda
Republican Clinical Hospital named after N.A. Semashko
Russian Federation

69, Kievskaya st., Simferopol, 295017


T. T. Dmitrieva
Kamchatka Regional Children’s Hospital
Russian Federation

7, Ordzhonikidze st., Petropavlovsk-Kamchatsky, 683024


E. R. Eremina
Republican Perinatal Center of the Ministry of Health of the Buryat Republic ; Buryat State University
Russian Federation

15b, Pirogov st., Ulan-Ude, 670047 

24a, Smolina st., Ulan-Ude, 670047 


T. N. Kekeeva
Research Centre for Medical Genetics ; Morozovskaya Children’s City Clinical Hospital of the Department of Healthcare of the City of Moscow
Russian Federation

1, Moskvorechye st., Moscow, 115522

1/9, 4th Dobryninsky per., Moscow, 119049


V. S. Lobanova
Morozovskaya Children’s City Clinical Hospital of the Department of Healthcare of the City of Moscow
Russian Federation

1/9, 4th Dobryninsky per., Moscow, 119049


L. N. Kolbasin
Surgut District Clinical Center for Maternal and Child Health
Russian Federation

15, Proletarsky av., Surgut, 628405


S. I. Papanov
Surgut District Clinical Center for Maternal and Child Health
Russian Federation

15, Proletarsky av., Surgut, 628405


Y. Y. Kotalevskaya
Moscow Regional Research and Clinical Institute («MONIKI»)
Russian Federation

61/2, Schepkina st., Moscow, 129110


K. Z. Revazyan
Moscow Regional Research and Clinical Institute («MONIKI»)
Russian Federation

61/2, Schepkina st., Moscow, 129110


D. V. Svetlichnaya
Moscow Regional Research and Clinical Institute («MONIKI»)
Russian Federation

61/2, Schepkina st., Moscow, 129110


A. A. Kotova
Children’s Regional Clinical Hospital
Russian Federation

23, Stepana Razina nab., Tver, 170100


E. M. Kochegurova
Tver State Medical University
Russian Federation

4, Sovetskaya st., Tver, 170100


E. L. Kubekova
Perinatal Center of the Ministry of Health of the Kabardino-Balkarian Republic
Russian Federation

34, Shogenova st., Nalchik, 360032


I. A. Kuzmicheva
Kaluga Regional Clinical Hospital
Russian Federation

1, building 6, Vishnevsky st., Kaluga, 248007


S. A. Matulevich
Research Institute Regional Clinical Hospital N1 named after professor S. V. Ochapovsky
Russian Federation

167, 1 May 1 st., Krasnodar, 350086


I. A. Dzemina
Research Institute Regional Clinical Hospital N1 named after professor S. V. Ochapovsky
Russian Federation

167, 1 May 1 st., Krasnodar, 350086


T. V. Melnikova
Samara Regional Clinical Hospital named after V.D. Seredavin
Russian Federation

159, Tashkentskaya st., Samara, 443095


M. A. Novik
Regional Perinatal Center of the Ministry of Health of the Kaliningrad region
Russian Federation

145, Kashtanovaya alley, Kaliningrad, 236023


O. S. Omzar
Research Institute of Medical and Social Problems and Management of the Republic of Tyva
Russian Federation

17, Ulug-Khemskaya st., Kyzyl, 667003


A. O. Dulush
Perinatal Center of the Republic of Tyva
Russian Federation

159A, Oyun Kursedi st., Kyzyl, 667003


O. P. Paveleva
Kurgan Regional Perinatal Center
Russian Federation

39, Karbysheva st., Kurgan, 640014


I. V. Potapova
Irkutsk Regional Clinical Hospital, Winner of the «Mark of the Honor» Award
Russian Federation

100, Microrayon Yubileinyi st., Irkutsk, 664078


D. Kh. Saydaeva
Republican Perinatal Center
Russian Federation

16A, Bulvar Dudaeva st., Grozny, 364068


E. A. Serebryakova
Diagnostic Center (Medical and Genetic)
Russian Federation

5A, Tobolskaya st., Saint Petersburg, 194044


E. S. Fedchuk
Lipetsk Regional Perinatal Center
Russian Federation

135, Gagarin st., Lipetsk, 398050


Y. D. Nazarenko
Research Centre for Medical Genetics
Russian Federation

1, Moskvorechye st., Moscow, 115522


S. N. Pchelina
Research Centre for Medical Genetics ; Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute» ; Pavlov First Saint Petersburg State Medical University
Russian Federation

1, Moskvorechye st., Moscow, 115522 

1, Orlova roshcha, Gatchina, 188300 

6-8, Lev Tolstoy st., Saint Petersburg, 197022 

 


E. Y. Zakharova
Research Centre for Medical Genetics
Russian Federation

1, Moskvorechye st., Moscow, 115522 


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Review

For citations:

Baranova P.V., Vasileva M.V., Bakin N.V., Moryakova N.V., Aksyanova Kh.F., Kolchina A.N., Astakhova T.A., Bairova T.A., Buyanova G.V., Pobedinskaya A.I., Vafina Z.I., Gamzatova A.I., Gorda M.V., Dmitrieva T.T., Eremina E.R., Kekeeva T.N., Lobanova V.S., Kolbasin L.N., Papanov S.I., Kotalevskaya Y.Y., Revazyan K.Z., Svetlichnaya D.V., Kotova A.A., Kochegurova E.M., Kubekova E.L., Kuzmicheva I.A., Matulevich S.A., Dzemina I.A., Melnikova T.V., Novik M.A., Omzar O.S., Dulush A.O., Paveleva O.P., Potapova I.V., Saydaeva D.Kh., Serebryakova E.A., Fedchuk E.S., Nazarenko Y.D., Pchelina S.N., Zakharova E.Y. Methylmalonic and Propionic Acidemias in the Expanded Newborn Screening Program in the Russian Federation: Evaluation of Diagnostic Performance and Algorithm Optimization. Medical Genetics. 2025;24(10):16-39. (In Russ.) https://doi.org/10.25557/2073-7998.2025.10.16-39

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