Blood Cytopenias As Manifestations of Inherited Metabolic Diseases: a Narrative Review

Overview

Journal Orphanet J Rare Dis

Publisher Biomed Central

Specialty General Medicine

Date 2024 Feb 14

PMID 38355710

Authors

Yannick Moutapam-Ngamby-Adriaansen

Francois Maillot

Francois Labarthe

Bertrand Lioger

Affiliations

Soon will be listed here.

Abstract

Inherited Metabolic Diseases (IMD) encompass a diverse group of rare genetic conditions that, despite their individual rarity, collectively affect a substantial proportion, estimated at as much as 1 in 784 live births. Among their wide-ranging clinical manifestations, cytopenia stands out as a prominent feature. Consequently, IMD should be considered a potential diagnosis when evaluating patients presenting with cytopenia. However, it is essential to note that the existing scientific literature pertaining to the link between IMD and cytopenia is limited, primarily comprising case reports and case series. This paucity of data may contribute to the inadequate recognition of the association between IMD and cytopenia, potentially leading to underdiagnosis. In this review, we synthesize our findings from a literature analysis along with our clinical expertise to offer a comprehensive insight into the clinical presentation of IMD cases associated with cytopenia. Furthermore, we introduce a structured diagnostic approach underpinned by decision-making algorithms, with the aim of enhancing the early identification and management of IMD-related cytopenia.

References

Briani C, Torre C, Citton V, Manara R, Pompanin S, Binotto G . Cobalamin deficiency: clinical picture and radiological findings. Nutrients. 2013; 5(11):4521-39. PMC: 3847746. DOI: 10.3390/nu5114521. View

Xia Y, Duan Y, Zheng W, Liang L, Zhang H, Luo X . Clinical, genetic profile and therapy evaluation of 55 children and 5 adults with sitosterolemia. J Clin Lipidol. 2021; 16(1):40-51. DOI: 10.1016/j.jacl.2021.11.015. View

Lokuhewage C, Pathiraja H, Madawala P, Bandara S, Mettananda S . Lysinuric protein intolerance presenting as pancytopenia and splenomegaly mimicking acute leukaemia: a case report. BMC Pediatr. 2023; 23(1):382. PMC: 10391768. DOI: 10.1186/s12887-023-04207-7. View

Hill A, Hill Q . Autoimmune hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2018; 2018(1):382-389. PMC: 6246027. DOI: 10.1182/asheducation-2018.1.382. View

Bermejo N, Prieto J, Arcos M . Sea-blue histiocytosis in bone marrow of a patient with chronic thrombocytopenia. Acta Haematol. 2014; 133(3):277-8. DOI: 10.1159/000366189. View

Iolascon A, De Falco L . Mutations in the gene encoding DMT1: clinical presentation and treatment. Semin Hematol. 2009; 46(4):358-70. DOI: 10.1053/j.seminhematol.2009.06.005. View

Ferreira C, Rahman S, Keller M, Zschocke J . An international classification of inherited metabolic disorders (ICIMD). J Inherit Metab Dis. 2020; 44(1):164-177. PMC: 9021760. DOI: 10.1002/jimd.12348. View

Lv Y, Lau W, Li Y, Deng J, Han X, Gong X . Hypersplenism: History and current status. Exp Ther Med. 2016; 12(4):2377-2382. PMC: 5038876. DOI: 10.3892/etm.2016.3683. View

Thiagarajan P, Parker C, Prchal J . How Do Red Blood Cells Die?. Front Physiol. 2021; 12:655393. PMC: 8006275. DOI: 10.3389/fphys.2021.655393. View

10.

Bottomley S, Fleming M . Sideroblastic anemia: diagnosis and management. Hematol Oncol Clin North Am. 2014; 28(4):653-70, v. DOI: 10.1016/j.hoc.2014.04.008. View

11.

Donker A, Raymakers R, Nieuwenhuis H, Coenen M, Janssen M, MacKenzie M . X-linked sideroblastic anaemia due to ALAS₂ mutations in the Netherlands: a disease in disguise. Neth J Med. 2014; 72(4):210-7. View

12.

Bayer G, Von Tokarski F, Thoreau B, Bauvois A, Barbet C, Cloarec S . Etiology and Outcomes of Thrombotic Microangiopathies. Clin J Am Soc Nephrol. 2019; 14(4):557-566. PMC: 6450353. DOI: 10.2215/CJN.11470918. View

13.

Hershkop E, Bergman I, Kurolap A, Dally N, Feldman H . Non-immune Hemolysis in Gaucher Disease and Review of the Literature. Rambam Maimonides Med J. 2021; 12(3). PMC: 8284991. DOI: 10.5041/RMMJ.10446. View

14.

Bruno M, De Falco L, Iolascon A . How I Diagnose Non-thalassemic Microcytic Anemias. Semin Hematol. 2015; 52(4):270-8. DOI: 10.1053/j.seminhematol.2015.05.002. View

15.

Seo A, Gulsuner S, Pierce S, Ben-Harosh M, Shalev H, Walsh T . Inherited thrombocytopenia associated with mutation of UDP-galactose-4-epimerase (GALE). Hum Mol Genet. 2018; 28(1):133-142. PMC: 6298239. DOI: 10.1093/hmg/ddy334. View

16.

Liskova A, Samec M, Koklesova L, Kudela E, Kubatka P, Golubnitschaja O . Mitochondriopathies as a Clue to Systemic Disorders-Analytical Tools and Mitigating Measures in Context of Predictive, Preventive, and Personalized (3P) Medicine. Int J Mol Sci. 2021; 22(4). PMC: 7922866. DOI: 10.3390/ijms22042007. View

17.

Zhou X, Cui Y, Han J . Methylmalonic acidemia: Current status and research priorities. Intractable Rare Dis Res. 2018; 7(2):73-78. PMC: 5982627. DOI: 10.5582/irdr.2018.01026. View

18.

Sabry W, Elemary M, Burnouf T, Seghatchian J, Goubran H . Vitamin B12 deficiency and metabolism-mediated thrombotic microangiopathy (MM-TMA). Transfus Apher Sci. 2020; 59(1):102717. DOI: 10.1016/j.transci.2019.102717. View

19.

Huemer M, Diodato D, Schwahn B, Schiff M, Bandeira A, Benoist J . Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency. J Inherit Metab Dis. 2016; 40(1):21-48. PMC: 5203859. DOI: 10.1007/s10545-016-9991-4. View

20.

Cario H, Smith D, Blom H, Blau N, Bode H, Holzmann K . Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Am J Hum Genet. 2011; 88(2):226-31. PMC: 3035706. DOI: 10.1016/j.ajhg.2011.01.007. View