Understanding Gaucher Disease: Genetics, Transmission, and Family Screening

Genetics and Epidemiology

Incidence and prevalence

• Type 1 (non-neuropathic) Gaucher disease is the most common form, with a prevalence of 1 in 50,000 to 100,000 individuals.¹ Although the disease is pan-ethnic, there is a high prevalence of type 1 Gaucher disease in certain ethnic groups, notably Ashkenazi Jews who have a prevalence of the disease of approximately 1 in 850 individuals.¹ Type 1 disease is estimated to account for >90% of all Gaucher patients.¹
• Type 2 diseases have a prevalence of <1 in 100,000 individuals, while in type 3 Gaucher disease this figure varies to <1 in 50,000 to 100,000.²
• Type 3 Gaucher disease has a higher prevalence reported in patients from the Norrbotten population in Sweden.³

However, as with any rare disease, it is difficult to know exactly how many people are actually affected.

Genotypes

More than 300 alleles carrying pathogenic variants have been identified in Gaucher disease.¹ The clinical expression of Gaucher disease cannot usually be accurately predicted by analysis of the pathogenic variant alone. For most pathogenic variants, the genotype/phenotype relationship is weak.

Probabilities of Gaucher disease transmission

Because Gaucher disease is autosomal recessive, a carrier has a 50% chance of passing on a gene with a pathogenic variant to each offspring. If both parents are carriers, there is a 25% chance that the child will not be affected by the disease and a 25% chance that the child will develop Gaucher disease.^{1, 4-7}

Situation in which both parents are carriers of Gaucher disease

Family screening

Since Gaucher disease is an inherited disease, if an individual has the disease it is very likely that other members of his family have at least one allele with the pathogenic variant of the gene that codes for acid β-glucosidase. It is very important that siblings of someone with Gaucher disease are tested, in case they are also affected.

Predicting the severity of the disease in a child is easier when parents already have a child with Gaucher disease, since there is a considerable degree of agreement between siblings. Occasionally, the degree of manifestation of the disease is completely different between siblings, but this is less common.⁴

If there are no children with Gaucher disease in the family, the genetics specialist relies on the genotype of the parents, who can provide some useful information. For example, if both parents are heterozygous for the pathogenic variant N370S, the probability of the future child not having neuropathic disease is very high.⁸

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