If you were to look up Gaucher disease on the OMIM website, you would see that there are three major types, designated Type I (OMIM 230800), Type II (OMIM 230900), and Type III (OMIM 231000). All three types are mutations of the gene for acid-β-glucosidase, encoded on chromosome 1. Different mutations of this gene produce the three types of Gaucher disease that differ somewhat in their symptoms and disease severity.

For each mutation, speculate about whether the acid-β-glucosidase enzyme is merely reduced in function or whether its production is eliminated, and explain why.

Key Concepts

Gaucher Disease Types

Gaucher disease is a genetic disorder caused by mutations in the gene encoding acid-β-glucosidase, leading to three major types: Type I, Type II, and Type III. Each type is characterized by varying symptoms and severity, with Type I being the most common and least severe, while Type II is the most severe and often fatal in infancy. Understanding these distinctions is crucial for analyzing the functional impact of specific mutations on the enzyme.

Acid-β-glucosidase Function

Acid-β-glucosidase is an enzyme responsible for breaking down glucocerebroside into glucose and ceramide. In Gaucher disease, mutations can lead to either a reduction in enzyme activity or complete loss of function. The degree of enzyme activity directly correlates with the severity of the disease, making it essential to assess whether mutations result in diminished function or total enzyme absence.

Genetic Mutations and Enzyme Activity

Genetic mutations can affect protein function in various ways, including missense mutations that alter amino acids, nonsense mutations that create premature stop codons, or frameshift mutations that disrupt the reading frame. These changes can lead to reduced enzyme activity or complete loss of production. Speculating on the nature of these mutations in Gaucher disease helps in understanding the clinical manifestations and potential treatment strategies.