Heterozygosity in NPC may be associated with neurologic and systemic phenotypes.

Background: Niemann-Pick disease type C (NPC) is a pan-ethnic, progressive, recessively inherited lysosomal disorder that affects 1:100,000 live births. Emerging biochemical, genetic, and clinical evidence challenges the traditional view that disease-associated variants in the genes associated with the typical phenotype NPC manifest as an exclusively autosomal recessive disorder. While biallelic pathogenic variants cause the NPC disease phenotype, heterozygous carriers may exhibit phenotypic traits attributable to a partial loss of Methods: We conducted a literature search of articles relevant to heterozygosity in NPC genes and genes associated with other lysosomal diseases. A narrative mini-review format was employed with the intention of providing a brief overview of the frequency of NPC carriers, as well as the biochemical, genetic, non-clinical, and clinical evidence available for readers seeking to understand the scientific basis for why NPC heterozygosity should be discussed and considered as a potential risk factor for the development of neurological phenotype or neurodegenerative diseases. Conclusion: Heterozygosity for many genes, including