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

Area of Science:

• Genetics
• Lysosomal Storage Disorders
• Neurodegenerative Diseases

Background:

• Niemann-Pick disease type C (NPC) is a rare, progressive lysosomal disorder.
• Emerging evidence suggests heterozygous carriers of NPC gene variants may exhibit phenotypic traits.
• This challenges the traditional view of NPC as exclusively autosomal recessive.

Purpose of the Study:

• To review evidence on NPC gene heterozygosity.
• To explore the frequency and clinical significance of NPC carriers.
• To discuss NPC heterozygosity as a potential risk factor for neurological conditions.

Main Methods:

• Literature search on NPC gene heterozygosity and other lysosomal diseases.
• Narrative mini-review format.
• Analysis of biochemical, genetic, and clinical evidence.

Main Results:

• Heterozygosity for NPC1 variants can be clinically significant.
• Carrier status may be linked to neurological phenotypes.
• Evidence supports considering NPC heterozygosity in disease development.

Conclusions:

• Recognizing NPC heterozygosity impacts diagnosis and management.
• Improved understanding broadens the genetic and phenotypic spectrum of NPC.
• Early intervention and targeted treatments benefit carriers and affected individuals.