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Sphingosine phosphate lyase insufficiency syndrome: a systematic review

Lookup NU author(s): Professor John SayerORCiD


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© 2022, Children's Hospital, Zhejiang University School of Medicine.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.

Publication metadata

Author(s): Pournasiri Z, Madani A, Nazarpack F, Sayer JA, Chavoshzadeh Z, Nili F, Tran P, Saba JD, Jamee M

Publication type: Review

Publication status: Published

Journal: World Journal of Pediatrics

Year: 2023

Volume: 19

Pages: 425-437

Print publication date: 01/05/2023

Online publication date: 12/11/2022

Acceptance date: 22/08/2022

ISSN (print): 1708-8569

ISSN (electronic): 1867-0687

Publisher: Zhejiang University School of Medicine Children's Hospital


DOI: 10.1007/s12519-022-00615-4