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Sphingosine phosphate lyase insufficiency syndrome: a systematic review

  • Systematic review
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Abstract

Background

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) or nephrotic syndrome type-14 is caused by biallelic mutations in SGPL1. Here, we conducted a systematic review to delineate the characteristics of SPLIS patients.

Methods

A literature search was performed in PubMed, Web of Science, and Scopus databases, and eligible studies were included. For all patients, demographic, clinical, laboratory, and molecular data were collected and analyzed.

Results

Fifty-five SPLIS patients (54.9% male, 45.1% female) were identified in 19 articles. Parental consanguinity and positive family history were reported in 70.9% and 52.7% of patients, respectively. Most patients (54.9%) primarily manifested within the first year of life, nearly half of whom survived, while all patients with a prenatal diagnosis of SPLIS (27.5%) died at a median [interquartile (IQR)] age of 2 (1.4–5.3) months (P = 0.003). The most prevalent clinical feature was endocrinopathies, including primary adrenal insufficiency (PAI) (71.2%) and hypothyroidism (32.7%). Kidney disorders (42, 80.8%) were mainly in the form of steroid-resistant nephrotic syndrome (SRNS) and progressed to end-stage kidney disease (ESKD) in 19 (36.5%) patients at a median (IQR) age of 6 (1.4–42.6) months. Among 30 different mutations in SGPL1, the most common was c.665G > A (p.Arg222Gln) in 11 (20%) patients. Twenty-six (49.1%) patients with available outcome were deceased at a median (IQR) age of 5 (1.5–30.5) months, mostly following ESKD (23%) or sepsis/septic shock (23%).

Conclusion

In patients with PAI and/or SRNS, SGPL1 should be added to diagnostic genetic panels, which can provide an earlier diagnosis of SPLIS and prevention of ESKD and other life-threatening complications.

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Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

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Author information

Authors and Affiliations

  1. Pediatric Nephrology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zahra Pournasiri, Fatemeh Nazarpack & Mahnaz Jamee

  2. Department of Pediatric Nephrology, Children’s Medical Center, Pediatric Chronic Kidney Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Abbas Madani

  3. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK

    John A. Sayer

  4. Renal Services, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK

    John A. Sayer

  5. NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, NE45PL, Tyne and Wear, UK

    John A. Sayer

  6. Immunology and Allergy Department, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, 15514-15468, Iran

    Zahra Chavoshzadeh & Mahnaz Jamee

  7. Department of Pathology, Imam Khomeini Complex Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Fatemeh Nili

  8. Allergy Immunology Division, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, USA

    Paulina Tran

  9. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA

    Paulina Tran

  10. Division of Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, CA, USA

    Julie D. Saba

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  1. Zahra Pournasiri
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Contributions

PZ contributed to conceptualization, methodology and data curation. MA, CZ, and TP contributed to reviewing and editing. SJA and SJD contributed to investigation, reviewing and editing. NF contributed to investigation. JM contributed to conceptualization, methodology, data curation, investigation, formal analysis, supervision, visualization, and original draft preparation. All the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Mahnaz Jamee.

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Ethical approval was not necessary for the performance of this review, as it involved secondary review of existing literature.

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Pournasiri, Z., Madani, A., Nazarpack, F. et al. Sphingosine phosphate lyase insufficiency syndrome: a systematic review. World J Pediatr 19, 425–437 (2023). https://doi.org/10.1007/s12519-022-00615-4

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