NOVEL HETEROZYGOUS PSMB8 MUTATION IN CANDLE SYNDROME: FIRST REPORT OF ASSOCIATED LOW NK CELL LEVELS

Abstract

Background: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a rare auto-inflammatory inherited type of condition classified in the past few years. The clinical manifestations are observed during the first year of life. Inherited mutations in the PSMB8 gene are reported to cause CANDLE syndrome. Methods: Detailed family and clinical histories were obtained. Genomic DNA was extracted from the whole blood. DNA Sanger sequencing was performed to identify disease-causing mutations in the gene PSMB8 (Proteasome subunit beta type-8). Complete Blood Count (CBC), Liver Function Test (LFT), blood culture, contrast tomography scan (CT) and ultrasound scrotum were performed. An expert dermatologist investigated nodular erythema or erythematous eruptions. Results: DNA Sanger sequencing revealed a heterozygous missense mutation in gene PSMB8 (c.599C>T). The patient's mother was homozygous for the missense mutation. High-grade episodic fever with low-fat levels (possibly lipodystrophy) was observed in body areas. Blood CBC revealed neutrophilia while the CT scan showed post-infective consolidation in the upper lobe of the posterior segment. Conclusion: The current study describes a novel heterozygous genetic mutation. Clinical investigations revealed disease features partially fulfilling the criteria. We also report here for the first time CANDLE syndrome with low levels of natural killer cells (NK cells).

Pak J Physiol 2024;20(4):28-31, DOI: https://doi.org/10.69656/pjp.v20i4.1769