Severe combined immunodeficiences: new and old scenarios

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Severe combined immunodeficiencies (SCIDs) are congenital disorders impacting cell-mediated or humoral immunity, leading to severe infections.
• SCID classification relies on T, B, and NK cell presence/absence to pinpoint differentiation blockages.

Purpose of the Study:

• To review SCID clinical heterogeneity and novel pathogenic mechanisms.
• To guide healthcare providers in recognizing less frequent SCID phenotypes for prompt diagnosis.

Main Methods:

• Literature review of SCID classification, clinical presentations, and genetic alterations.
• Analysis of diagnostic approaches and emerging pathogenetic mechanisms.

Main Results:

• SCID patients exhibit common features like infections and failure to thrive, but novel gene alterations reveal complex phenotypes.
• Uncommon clinical signs and extrahematopoietic manifestations can be specific to certain SCID forms.

Conclusions:

• Early recognition of diverse SCID phenotypes, including rare presentations, is vital.
• Integrating knowledge of novel genetic causes and clinical features improves diagnostic accuracy for SCID.