Skip to main content

Advertisement

SpringerLink
Log in

Familial hemophagocytic lymphohistiocytosis syndrome due to lysinuric protein intolerance: a patient with a novel compound heterozygous pathogenic variant in SLC7A7

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Lysinuric protein intolerance (LPI) (MIM#222700) is a rare autosomal recessive defect in bibasic amino acid transport caused by pathogenic variants in solute carrier family 7 member 7 gene ( SLC7A7). The symptoms begin after weaning from breast milk and include refusal of feeding, vomiting, and consequent failure to thrive. Some metabolic disorders, including LPI, are complicated by hemophagocytic lymphohistiocytosis (HLH); however, the frequency of HLH caused by inborn errors of metabolism is very rare in the HLH cohort. SLC7A7 consists of 11 exons, and has 66 known pathogenic variants. SLC7A7 is associated with HLH. Here, we report the case of a 32-year-old woman who presented with LPI and HLH. Genetic analysis revealed a novel compound heterozygosity in SLC7A7 with two pathogenic variants, c.713C>T (p. Sre238Phe) and c.625+1G>A (splicing acceptor site) inherited from her father and mother, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

LPI:

Lysinuric protein intolerance

SLC7A7 :

Solute carrier family 7 member 7 gene

y+L AT-1:

Y+L amino acid transporter-1

HLH:

Hemophagocytic lymphohistiocytosis

HGMD:

Human genome database

IEM:

Inborn errors of metabolism

EBV:

Epstein–Barr virus

VCA:

Viral capsid antigen

ANA:

Antinuclear antibody

SS:

Sjögren syndrome

HbA1c :

Hemoglobin A1c

anti-dsDNA:

Anti-double stranded DNA

SLE:

Systemic lupus erythematosus

COG6:

Component of oligomeric Golgi complex 6

References

  1. Torrents D, Mykkänen J, Pineda M, Feliubadaló L, Estévez R, de Cid RD, et al. Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. Nat Genet. 1999;21:293–6.

    Article  CAS  Google Scholar 

  2. Noguchi A, Takahashi T. Overview of symptoms and treatment for lysinuric protein intolerance. J Hum Genet. 2019;64:849–58.

    Article  Google Scholar 

  3. Yahyaoui R, Pérez-Frías J. Amino acid transport defects in human inherited metabolic disorders. Int J Mol Sci. 2019;21:119.

    Article  Google Scholar 

  4. Carpentieri D, Barnhart MF, Aleck K, Miloh T, deMello D. Lysinuric protein intolerance in a family of Mexican ancestry with a novel SLC7A7 gene deletion. Case report and review of the literature. Mol Genet Metab Rep. 2015;2:47–50.

    Article  CAS  Google Scholar 

  5. Morimoto A, Nakazawa Y, Ishii E. Hemophagocytic lymphohistiocytosis: Pathogenesis, diagnosis, and management. Pediatr Int. 2016;58:817–25.

    Article  CAS  Google Scholar 

  6. Althonaian N, Alsultan A, Morava E, Alfadhel M. Secondary hemophagocytic syndrome associated with COG6 gene defect: report and review. JIMD Rep. 2018;42:105–11.

    Article  Google Scholar 

  7. Gadoury-Levesque V, Dong L, Su R, Chen J, Zhang K, Risma KA, et al. Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders. Blood Adv. 2020;4:2578–94.

    Article  CAS  Google Scholar 

  8. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.

    Article  Google Scholar 

  9. Baralle D, Baralle M. Splicing in action: assessing disease causing sequence changes. J Med Genet. 2005;42(10):737–48.

    Article  CAS  Google Scholar 

  10. Baronio F, Conti F, Miniaci A, Carfagnini F, Di Natale V, Di Donato G, et al. Diagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis. Mol Genet Metab Rep. 2022;30: 100833.

    Article  CAS  Google Scholar 

  11. Bartakke S, Nisal A, Bafna V, Valecha A. Secondary hemophagocytic lymphohistiocytosis in an Infant with Wolman Disease. Indian J Hematol Blood Transfus. 2021;37(1):191–2.

    Article  Google Scholar 

  12. Alabbas F, Elyamany G, Alanzi T, Ali TB, Albatniji F, Alfaraidi H. Wolman’s disease presenting with secondary hemophagocytic lymphohistiocytosis: a case report from Saudi Arabia and literature review. BMC Pediatr. 2021;21(1):1–6.

    Article  Google Scholar 

  13. Gokce M, Unal O, Hismi B, Gumruk F, Coskun T, Balta G, et al. Secondary hemophagocytosis in 3 patients with organic acidemia involving propionate metabolism. Pediatric Hematol Oncol. 2012;29(1):92–8.

    Article  CAS  Google Scholar 

  14. Karaman S, Urganci N, Kutluk G, Cetinkaya F. Niemann – Pick disease associated with hemophagocytic syndrome. Turk J Haematol. 2010;27(4):303–7.

    Article  Google Scholar 

  15. Tangye SG, Al-Herz W, Bousfiha A, Chatila T, Cunningham-Rundles C, Etzioni A, et al. Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2020;40(1):24–64.

    Article  Google Scholar 

  16. Duval M, Fenneteau O, Doireau V, Faye A, Emilie D, Yotnda P, et al. Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. J Pediatr. 1999;134(2):236–9.

    Article  CAS  Google Scholar 

  17. Gordon WC, Gibson B, Leach MT, Robinson P. Haemophagocytosis by myeloid precursors in lysinuric protein intolerance. Br J Haematol. 2007;138:1.

    Article  Google Scholar 

  18. Taurisano R, Maiorana A, De Benedetti F, Dionisi-Vici C, Boldrini R, Deodato F. Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation. Eur J Pediatr. 2014;173:1391–4.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Drs. Mamiko Yamada, Hisato Suzuki, and Toshiki Takeuchi (Center of Medical Genetics, Keio University School of Medicine) for patient genetic analysis. We also thank all the medical staff of Shiga University of Medical Science involved in the treatment of this patient.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan

    Yukihiro Matsukawa, Kenichi Sakamoto, Yuhachi Ikeda, Takashi Taga & Yoshihiro Maruo

  2. Center of Medical Genetics, Keio University School of Medicine, Tokyo, Japan

    Kenjiro Kosaki

Authors
  1. Yukihiro Matsukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenichi Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuhachi Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Taga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kenjiro Kosaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshihiro Maruo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YM. and KS. collected and interpreted the data and wrote the manuscript; TT. and YM. designed the study, interpreted the data, wrote the manuscript, and provided medical care for this patient; KK. evaluated the patient and collected data. All authors discussed the results and critically reviewed the manuscript.

Corresponding author

Correspondence to Kenichi Sakamoto.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 23 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsukawa, Y., Sakamoto, K., Ikeda, Y. et al. Familial hemophagocytic lymphohistiocytosis syndrome due to lysinuric protein intolerance: a patient with a novel compound heterozygous pathogenic variant in SLC7A7. Int J Hematol 116, 635–638 (2022). https://doi.org/10.1007/s12185-022-03375-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-022-03375-z

Keywords

Search

Navigation