The patient journey
with Fabry disease

Fabry disease has a profound emotional and physical impact on affected individuals and their families.¹ Disease manifestations in patients with the same gene mutation, even males from the same family, may vary, making counselling difficult.¹ 

Alongside the physical symptoms, patients can feel anxiety concerning disease progression, guilt related to passing the disease on to children, and other strong emotions such as anger, grief or hopelessness.¹ Their self-esteem and self-identity can also be affected.¹ Genetic counselling is critical following diagnosis to provide patients with a better understanding of their condition.¹ 

The conception of the expression of Fabry disease in females has drastically changed over the last decade.² Female heterozygotes were erroneously described as “carriers of the defective gene” more or less safeguarded against developing disease manifestations and symptoms.³ 

Disease expression in females is variable, and clinical phenotypes range from asymptomatic patients to women with disease manifestations as severe as observed in classically affected males.²  

In female patients with Fabry disease: 

Screening family members 

Clinical and genetic screening of the at-risk members of families of newly diagnosed patients is of critical importance, as additional family members with Fabry disease may be identified from each individual index patient. One pedigree review study found that, on average, there were at least five family members diagnosed with Fabry disease following the diagnosis of a patient.¹  

Fabry disease inheritance patterns 

Parents should be informed about the likelihood that siblings, relatives, and future children will inherit the disease. Affected mothers have a 50% chance of passing the defective gene on to all offspring whether boys or girls. Sons who inherit the gene will be affected; her daughters may display a spectrum of clinical involvement.²  

Fathers with Fabry disease pass on the defective gene to none of their sons and all of their daughters. Previously unrecognized family members, males and females, can be identified at an early stage of the disease via screening for the mutation among family members.² 

Family planning 

Pre-conception or prenatal genetic counselling should be offered to all male and female patients of reproductive age, discussing Fabry disease's X-linked pattern of inheritance, availability of both prenatal diagnosis using cultured amniocytes or chorionic villi for molecular testing and preimplantation genetic diagnosis for selection of unaffected embryos.¹  

Pre-conception genetic counselling is important when pregnancy is being considered, as some adjunctive therapies routinely used to treat Fabry symptoms are teratogenic and may pose a risk to fetal development.¹ 

References:  

1. Ortiz A, et al. Mol Genet Metab. 2018;123(4):416-427.  
2. Martins, AM, et al. The Journal of pediatrics. 2009;155(4): S19-S31. 
3. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.