Autosomal Recessive Congenital Ichthyosis and Steroid-Resistant Nephrotic Syndrome due to Homozygous Mutation in the ALOX12B gene: A Novel Association with Review of Literature

Abstract

Nephrotic syndrome (NS) associated with autosomal recessive congenital ichthyosis (ARCI) is a rare association. In this article, we described a 4-year-old boy with steroid-resistant NS (SRNS) who had a history of ichthyotic skin lesions since birth. Renal biopsy revealed focal segmental glomerulosclerosis (tip variant). The skin biopsy was consistent with the findings of ichthyosis. Next-generation sequencing revealed a homozygous pathogenic variant (c.1625_1626del) in the exon 12 of the ALOX12B gene, confirming the diagnosis of ARCI2. The ALOX12B gene belongs to the lipoxygenase family and has a pivotal role in the formation of lipid layers in the epidermis. Leukotrienes have a counter-regulatory effect within the inflamed glomeruli, which influences the vascular tone and glomerular basement membrane permeability, that can be implicated in the pathogenesis of the NS. This child is currently in remission, on tacrolimus and low-dose prednisolone, with emollients and is on regular follow-up. SRNS associated with congenital ichthyosis secondary to a mutation in the ALOX12B gene has never been reported so far. The knowledge regarding this novel association will help the treating physicians in diagnosing this condition early, which will enable proper genetic counseling and prognostication of the disease to the family.

Keywords

autosomal recessive congenital ichthyosis - calcineurin inhibitors - focal segmental glomerulosclerosis - nephrotic syndrome

Note

Informed consent was obtained from the parents of the child. This article does not contain any studies with human participants or animals performed by any of the authors.

Authors' Contributions

L.D. collected clinical data, designed the study, reviewed the literature, and wrote the manuscript. A.K. performed and analyzed the genetic analysis. R.N. examined and reviewed the renal biopsy. S.C. collected clinical data. S.H. supervised overall concept design and critical review of the article for important intellectual content and final approval of the manuscript. I.K.S. supervised overall concept design, critical review of the article for important intellectual content, and final approval of the manuscript. K.T. supervised overall concept design, critical review of the article for important intellectual content, and final approval of the manuscript. All the authors revised and approved the final version of the manuscript.

Publication History

Received: 20 August 2020

Accepted: 12 September 2020

Article published online:
19 October 2020

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