Recognizing RENI Syndrome: A Case of Adrenal Insufficiency, Ichthyosis, and Proteinuria
https://doi.org/10.15605/jafes.041.S1
- Author:
Noor Zakirah Noordin
1
;
Saw Shi Hui
1
;
Noor Arliena binti Mat Amin
2
Author Information
1. Paediatric Department, Hospital Raja Permaisuri Bainun
2. Paediatric Department, Hospital Tunku Azizah
- Publication Type:Journal Article
- MeSH:
Adrenal Insufficiency;
Proteinuria;
Ichthyosis
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):143-144
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:RENI syndrome (renal, endocrine, neurologic, and immune
syndrome), also known as sphingosine-1-phosphate
lyase insufficiency syndrome (SPLIS), is a rare autosomal
recessive disorder caused by pathogenic variants in
the SGPL1 gene. This gene encodes sphingosine-1-
phosphate lyase, an enzyme responsible for the final step
in sphingolipid degradation. Impaired enzyme activity
results in the accumulation of sphingolipid intermediates,
leading to multisystem involvement affecting the kidneys,
adrenal glands, skin, immune system, and nervous system.
Frequently reported manifestations include steroid-resistant
nephrotic syndrome, primary adrenal insufficiency,
ichthyosis, and neurological abnormalities.
Case:We report a 15-year-old male with a history of primary
adrenal insufficiency diagnosed at age three after
presenting with recurrent vomiting and abdominal pain.
He was started on steroid replacement therapy and
remained stable without episodes of adrenal crisis. He
also had ichthyosis requiring dermatological follow-up.
During routine surveillance, persistent proteinuria was
detected, and urinary protein excretion increased over time. Ultrasound showed renal parenchymal changes
despite preserved renal function. Whole-exome sequencing
identified a homozygous variant of uncertain significance
in the SGPL1 gene, consistent with RENI syndrome. He
was started on enalapril for his proteinuria and continues
to undergo multidisciplinary follow-ups. Both parents are
consanguineous, but were not screened.
Mutations in SGPL1 have increasingly been recognized as a
monogenic cause of syndromic steroid-resistant nephrotic
syndrome, associated with endocrine and dermatological
features. Renal histopathology in cases reported often
shows focal segmental glomerulosclerosis, reflecting
podocyte injury due to disruption of sphingolipid signaling
pathways. Early recognition is crucial, as patients need
multidisciplinary care.
Conclusion:This case highlights the importance of considering RENI
syndrome in patients presenting with early-onset primary
adrenal insufficiency accompanied by renal and dermatological symptoms. Increased clinical awareness and prompt
genetic testing can enable earlier diagnosis, guide long-term
monitoring, and support appropriate genetic counseling.
- Full text:2026081013580124146EP_P017.pdf
