Discussion: This case highlights the diagnostic challenges of NPD type A, given its non-specific early presentation. The novel SMPD1 variant expands the known mutational spectrum of this disorder and provides insight into genotype-phenotype correlations. The presence of hepatosplenomegaly, growth restriction, and neuromuscular decline underscores the importance of early suspicion in pediatric patients with unexplained abdominal distension and developmental regression. While specific therapies remain limited, early genetic confirmation facilitates appropriate counseling, anticipatory guidance, and consideration of future therapeutic options such as enzyme replacement or substrate reduction therapy.

Conclusion: We present the first reported Saudi case of NPD type A caused by a novel SMPD1 mutation at chromosome 11p15.4. This case underscores the necessity of raising clinical awareness, strengthening genetic screening programs, and enhancing international data-sharing to improve early recognition and outcomes in rare lysosomal storage disorders.