AlSayed_2025_Orphanet.J.Rare.Dis__

BACKGROUND: Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive ultrarare lysosomal storage disease caused by pathogenic/likely pathogenic variants in the LIPA gene. The age of onset and progression rate can significantly vary, possibly due to the nature of the underlying variants. The disorder is often misdiagnosed or undiagnosed in the Gulf Cooperation Council (GCC) countries owing to its nonspecific clinical presentation; this necessitates establishing campaigns to increase awareness among healthcare professionals and strategies for identifying and screening high-risk populations. This narrative review is based on an analysis of the available literature, complemented by key discussions among a group of recognized healthcare professionals from the GCC region with expertise in clinical genetics, hepatology, gastroenterology, and lipidology. The outcome of their discussions is a set of practical recommendations and insights aimed at assisting physicians across multiple specialties in the identification and management of individuals affected by this ultrarare genetic disorder. CONCLUSION: LAL-D presents significant diagnostic and management challenges, particularly within the GCC region, owing to its rarity, limited awareness, and insufficient utilization of genetic testing. The prevalence and distribution of genetic variations associated with LAL-D remain inadequately explored in this population. The development of standardized regional guidelines is essential to harmonize diagnostic and management practices. Continued research efforts focusing on the genetic landscape of LAL-D in the GCC are imperative to bridge knowledge gaps and enhance clinical outcomes for affected patients.