Trusted Information on Fabry disease

Fabry disease is a genetic condition that causes progressive health issues. Fabry disease impacts the skin, nerves, kidneys, heart, and brain in both men and women. Fabry disease occurs when an individual has a disease-causing change (pathogenic variant/mutation) in the GLA gene resulting in the body making too little of a specific enzyme called alpha-galactosidase A or A-gal. If there is not enough of this enzyme, the body is unable to break down certain large molecules such as globotriaosylceramide (GL-3/Gb3) and so they build up in the cells that line blood vessels and other parts of the body. This build up narrows the blood vessels, interferes with cell function, and causes cells to send out distress signals to the immune system.

Fabry disease related health issues can start at any age. Based on the timing of when symptoms begin and the combination of the medical issues, Fabry disease is divided into 2 types: classic Fabry disease and non-classic, also called later-onset, Fabry disease. Classic Fabry disease symptoms typically begin in childhood and progress to end organ damage in early adulthood. Nonclassic Fabry disease symptoms usually begin after childhood and can be more variable.

Common Questions for Fabry disease …

Diagnosis and Testing

What tests are used to monitor Fabry disease?

Although different Fabry specialists and centers may vary slightly in their test and time schedule. Current accepted and recommended global studies to evaluate Fabry-related symptoms exist and may be performed on an annual basis:

CBC, platelet count, serum creatinine + BUN, GL3 (blood and urine), Lyso-GL3, thyroid studies, and a basic metabolic chemistry panel
Routine Urinalysis
24 hour Urine with creatinine, glomerular filtration rate, and protein clearance
Random urine measuring total protein and creatinine levels
EKG
Echocardiogram
Cardiac MRI (at baseline and as indicated)
Brain MRI or Head CT (at baseline and as indicated)
Hearing test
Eye exams
Pulmonary function tests
Depression/Anxiety assessment

For additional questions about these monitoring tests and when they should be scheduled, please refer to your Fabry doctor or a genetic counselor. In order to find a Fabry disease specialist or more information on Fabry disease treatment, please refer to the National Fabry Disease Foundation online resource.

References

Fabry Disease: A Guide for the Newly Diagnosed. (2006, January 1). Retrieved November 22, 2019, from http://genetics.emory.edu/documents/lsdc/factsheet44.pdf.
Mehta, A. (2017, January 5). Fabry Disease. Retrieved November 22, 2019, from http://www.ncbi.nlm.nih.gov/books/NBK1292/.
Fabry disease revisited: Management and treatment recommendations for adult patients. Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, Eng C, Hopkin RJ, Laney D, Linhart A, Waldek S, Wallace E, Weidemann F, Wilcox WR. Mol Genet Metab. 2018 Apr;123(4):416-427. doi: 10.1016/j.ymgme.2018.02.014. Epub 2018 Feb 28. Review. https://www.sciencedirect.com/science/article/pii/S1096719217307680?via%3Dihub Retrieved 12DEC19.

Why does it take so long for some people to be diagnosed with Fabry disease?

Fabry disease can take a long time to be diagnosed because the symptoms are not very specific and they overlap with other more common diseases, like chronic fatigue syndrome and irritable bowel syndrome. People may be called hypochondriacs or told symptoms are “all in their head” because many standard lab tests and assessments can’t detect Fabry disease. Fabry disease is considered a rare disease and it is often not in the list of possible causes for health problems. Many people with Fabry disease are given a symptom-specific diagnosis or a misdiagnosis until an eye finding, a kidney biopsy, or a family member is diagnosed with Fabry disease leading to the right diagnosis.

References

Emory University Fabry disease FAQs. Retrieved from http://genetics.emory.edu/resources/fact-sheets.html
Fabry Patient Education Retrieved from https://www.fabrycommunity.com/en/Patients/Education/Diagnosed.aspx
GeneReviews-Fabry Disease (n.d) Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1292/
Fabry testing roadmap” https://dev.genetics.emory.edu/docs/Fabry-Roadmap-4-05.pdf[/link

Is my lipid panel abnormal because I have Fabry disease?

The compounds that build up in the body with Fabry disease are called globotriaosylceramide (GL-3) and lyso-globotriaosylceramide (lyso-GL3). Lyso-GL3 and GL-3 are not the same as cholesterol or triglycerides and are not impacted by the food people eat. Having high, harmful “bad” LDL cholesterol or high triglycerides is not part of Fabry disease. However, whether or not someone has Fabry disease, having high triglycerides or LDL cholesterol does increase the risk for a person to have heart problems. So, even though Fabry disease doesn’t make it more likely for a person to have high LDL cholesterol issues or dyslipidemia, everyone with Fabry disease should have their cholesterol levels checked so that if it is high they can be treated by their doctor.

For additional questions about these lipid monitoring tests and when they should be scheduled, please refer to a Fabry doctor or genetic counselor. In order to find a Fabry disease specialist or more information on Fabry disease, please refer to the National Fabry Disease Foundation online resource.

References

Laney et al, Characterization Of Fasting Lipid Profiles in Patients with Fabry Disease, WORLD meeting, 2012.
Cartwright, DJ.; Cole, AL.; Cousins, AJ. & Lee, PJ. (2004). Raised HDL cholesterol in Fabry disease: response to enzyme replacement therapy. J Inherit Metab Dis., Vol. 6, No. 27, (2004), pp. 791-793, ISSN 0141-8955
Clarke JT; Stoltz JM & Mulcahey MR. (1976). Neutral glycosphingolipids of serum lipoproteins in Fabry’s disease. Biochim Biophys Acta., Vol. 2, No. 431, (May 1976), pp. 317-325, ISSN 0006-3002
Fabry disease symptoms http://www.fabrydisease.org/index.php/about-fabry-disease/fabry-disease-symptoms-overview

Treatment

How soon after starting enzyme replacement therapy for Fabry disease can I transition to home care?

Most doctors prefer that people who have Fabry disease begin enzyme replacement therapy (ERT) infusions in a hospital or outpatient infusion center. After a period of time – determined by the ordering doctor (usually three to six months or seven to 12 infusions) – many patients have the option to move to home infusions for their therapy.

The waiting period before moving to a home setting for infusions is to make sure the patients are comfortable with infusions and the doctors have time to manage any infusion-associated reactions (IARs) that may occur. Not all people receiving ERT will have IARS, but in clinical trials with Fabrazyme, 59% of patients reported IARs, some of which were severe. Doctors will be looking for signs of IARs so that they can manage them prior to referring patients to home infusions.

References

Smid BE, Hoogendijk SL, Wijburg FA, Hollak CE, Linthorst GE. A revised home treatment algorithm for Fabry disease: influence of antibody formation. Mol Genet Metab. 2013 Feb;108(2):132-7. doi: 10.1016/j.ymgme.2012.12.005. Epub 2012 Dec 28. PMID: 23332169 https://www.ncbi.nlm.nih.gov/pubmed/23332169
Kisinovsky I, Cáceres G, Coronel C, Reisin R. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina. Medicina (B Aires). 2013;73(1):31-4. http://www.medicinabuenosaires.com/PMID/23335703.pdf
Beck M, Gaedeke J, Martus P, Karabul N, Rolfs A. [Home-based infusion therapy–a feasible approach for chronically ill patients? A new path to provide superior patient care exemplified for Fabry’s disease]. Dtsch Med Wochenschr. 2013 Nov;138(46):2345-50. doi: 10.1055/s-0033-1349624. Epub 2013 Nov 5. German. PMID: 24193859 https://www.ncbi.nlm.nih.gov/pubmed/24193859
Sanofi-Genzyme, Fabrazyme® (agalsidase beta) Home Infusion Therapy: Risk Minimisation Information for Patients Manual for Patients with Fabry Disease who Receive Home Infusion of Fabrazyme. Version No. 1.3 (UK): March 2018 https://www.medicines.org.uk/emc/rmm/290/Document
Milligan A, Hughes D, Goodwin S, Richfield L, Mehta A. Intravenous enzyme replacement therapy: better in home or hospital? Br J Nurs. 2006 Mar 23-Apr 12;15(6):330-3. PMID: 16628169 https://www.ncbi.nlm.nih.gov/pubmed/16628169?report=abstract
Fabrazyme (agalsidase beta) Package Insert http://products.sanofi.us/Fabrazyme/Fabrazyme.pdf

I have Fabry disease; are home infusions right for me?

Home infusions can be a convenient option for many patients living with Fabry disease and receiving enzyme replacement therapy (ERT). When starting ERT, most doctors prefer that patients begin infusions in a hospital or outpatient infusion center. After a period of time – determined by the ordering doctor (usually three to six months) – patients may have the option to transition to home infusions. Patients might be a candidate for home infusion if:

They are stable patients who are not having active infusion-associated reactions (often called IARs).
They have a safe home environment for the infusions.
They have coverage for home infusions and medications through insurance or a patient-assistance program.

If a doctor has decided that a patient is a candidate for home infusions, the next step is working with the drug manufacturer’s patient-service programs and case managers or infusion pharmacies that provide case management. These specialized teams will investigate home-health nursing options to find one that accepts the patient’s insurance, is experienced in ERT, and fits their schedule. Most insurance companies allow home infusion therapy as an alternative to a hospital outpatient infusion center, and these experts will make sure home infusion will work with your insurance plan.

References

Guest JF, Jenssen T, Houge G, Aaseboe W, Tøndel C, Svarstad E. Modelling the resource implications of managing adults with Fabry disease in Norway favours home infusion. Eur J Clin Invest. 2010 Dec;40(12):1104-12. doi: 10.1111/j.1365-2362.2010.02363.x. Epub 2010 Sep 9. PMID: 21070219 https://www.ncbi.nlm.nih.gov/pubmed/21070219
Smid BE, Hoogendijk SL, Wijburg FA, Hollak CE, Linthorst GE. A revised home treatment algorithm for Fabry disease: influence of antibody formation. Mol Genet Metab. 2013 Feb;108(2):132-7. doi: 10.1016/j.ymgme.2012.12.005. Epub 2012 Dec 28.PMID: 23332169 https://www.ncbi.nlm.nih.gov/pubmed/23332169
Kisinovsky I, Cáceres G, Coronel C, Reisin R. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina. Medicina (B Aires). 2013;73(1):31-4. PMID: 23335703 http://www.medicinabuenosaires.com/PMID/23335703.pdf
Beck M, Gaedeke J, Martus P, Karabul N, Rolfs A. [Home-based infusion therapy–a feasible approach for chronically ill patients? A new path to provide superior patient care exemplified for Fabry’s disease]. Dtsch Med Wochenschr. 2013 Nov;138(46):2345-50. doi: 10.1055/s-0033-1349624. Epub 2013 Nov 5. German. PMID: 24193859 https://www.ncbi.nlm.nih.gov/pubmed/24193859
Milligan A, Hughes D, Goodwin S, Richfield L, Mehta A. Intravenous enzyme replacement therapy: better in home or hospital? Br J Nurs. 2006 Mar 23-Apr 12;15(6):330-3. PMID: 16628169 https://www.ncbi.nlm.nih.gov/pubmed/16628169?report=abstract

What do people do to treat the gastrointestinal issues seen in Fabry disease?

The GI symptoms in Fabry are thought to be caused by the storage of globotriaosylceramidee (GL-3) in the body that interferes with nerve and cell function in the GI system. This disrupts how fast the stomach empties, how quickly food moves through the intestine, and other functions of digestion including absorbing nutrients. Treatment with enzyme replacement therapy [Fabrazyme (agalsidase beta) or Replagal (agalsidase alfa)] or chaperone therapy [Galafold (migalastat)] has been shown to help decrease the severity and frequency of GI symptoms.

After an evaluation by a gastroenterologist and the ruling out other non-Fabry related causes of GI issues, doctors may also try symptom-specific medications such as: Reglan (metoclopramide) to help the stomach empty, Zofran (Ondansetron) to reduce nausea and vomiting, pancreatic enzymes to aid digestion, Loperamide (Imodium) to decrease hyperactive contractions in patients with diarrhea, or Amitriptyline to decrease nerve pain and other issues in the GI system. Some individuals with Fabry also find that eating small meals, taking probiotics, and avoiding spicy, lactose-containing, or greasy foods also help decrease GI issues.

References

Emory University GI Fact Sheet, updated 7/9/2015
Mehta, A. (2017, January 5). Fabry Disease. Retrieved November 22, 2019, from http://www.ncbi.nlm.nih.gov/books/NBK1292/.
Discover Fabry. (n.d.). Retrieved November 22, 2019, from https://www.discoverfabry.com/.

Clinical Research and Studies

How do I find gene therapy studies for Fabry disease?

Gene therapy studies in Fabry disease are open to enrolling people with Fabry disease in the United States, Canada, Australia, and other countries. Most of the studies are focused on men with classic Fabry disease at this time, but in future studies, women with classic Fabry disease and individuals living with non-classic Fabry disease will be included as well. There are several companies (4DMT, Freeline, Sangamo) exploring different methods of doing gene therapy for Fabry disease, so it is important to discuss the risks and benefits with a doctor familiar with the options to see which appears to make the most sense for a specific individual.

The easiest way to learn if you are a candidate for a gene therapy trial in Fabry disease is to talk to a healthcare provider that specializes in Fabry disease. However, studies focusing on gene therapy are also posted at clinicaltrials.gov where you can search for “Gene Therapy Fabry disease.” It may help to avoid limiting your search to your state or country, as many studies will pay for your travel if you are eligible to join.

References

Gene Therapy for Fabry disease. Fabry Disease News. https://fabrydiseasenews.com/gene-therapy-for-fabry-disease/ Accessed 12DEC2019

When should we begin enzyme replacement therapy for our children with Fabry Disease?

The timing of initiation for enzyme replacement therapy (ERT) can vary depending on the wishes of the family, the child’s symptoms, and the opinions of the doctor. Often, the treating physician will closely monitor gastrointestinal, kidney, and heart functions while also asking questions about the child’s energy and pain. They often recommend beginning ERT when symptoms of the disease emerge and begin to affect daily life and when symptoms begin to progress. The parents’ wishes are always taken into account when determining the time to begin therapy. At this time, therapy rarely starts before three years of age. Please talk to your Fabry doctor or genetic counselor to come up with the best treatment and monitoring plan.

References

Mehta, A. (2017, January 5). Fabry Disease. Retrieved November 22, 2019, from http://www.ncbi.nlm.nih.gov/books/NBK1292/.
National Fabry Disease Foundation. (n.d.). Retrieved from http://www.fabrydisease.org.

Living with Your Condition

If I have Fabry disease, do I have to stop smoking?

Smoking increases the risk of kidney failure, strokes, heart attacks, lung cancer, and respiratory illness. Since individuals with Fabry disease are already at increased risk for stroke, heart attack, kidney failure, and lung problems, it is recommended to stop smoking. Individuals with Fabry disease can talk to their doctor about safe strategies for quitting smoking.

References

Fabry Disease and the Kidneys. (2015, July 9). Retrieved November 22, 2019, from http://genetics.emory.edu/documents/resources/Fabry_Disease_and_Kidney_Function.pdf.
Mehta, A. (2017, January 5). Fabry Disease. Retrieved November 22, 2019, from http://www.ncbi.nlm.nih.gov/books/NBK1292/.

What should I tell the school about my child’s Fabry disease?

Teachers, particularly physical education teachers, and coaches, should understand the symptoms of Fabry disease and how a child is functioning physically. A child’s teachers should be informed about any medications and the special needs of Fabry patients, such as the necessity to avoid overheating during times like recess or physical education. Make sure that the school has updated medical files and explain expectations if a child gets ill at school. It is important to emphasize that children with Fabry disease do not have an increased risk for learning disabilities and that Fabry disease cannot “infect” other children.

For more information about how to talk to your child’s teacher or school about Fabry disease, please refer to the Fabry Support and Information Group or the National Disease Foundation. For further resources and books that can help explain Fabry disease to classmates and teachers, please visit the Emory Fabry Center’s resources webpage.

References

Emory University Fabry in Children Fact Sheet, updated 7/9/2015
Laney DA, Peck DS, Atherton AM, Manwaring LP, Christensen KM, Shankar SP, Grange DK, Wilcox WR, Hopkin RJ. Fabry disease in Infancy and Early Childhood: A systematic literature review. Genetics in Medicine. 2015 May;17(5):323-30. doi: 10.1038/gim.2014.120. Epub 2014 Sep 18.
Discover Fabry. (n.d.). Retrieved November 22, 2019, from https://www.discoverfabry.com/.

What are the advantages of home infusion for Fabry disease?

For people who have Fabry disease, home infusions of enzyme replacement therapy (ERT) can be a safe and practical way to reduce the burden of treatment. The advantages of home infusion may include:

Reduction of work and school absences with flexible scheduling
Personalized care with more one-on-one nurse time
Increased ease in staying on an infusion schedule with expanded scheduling time options
Increased quality of life related to decreased disruption of daily activities
Decreased therapy delivery costs as home infusions are often less expensive than outpatient hospital infusions

Having said this, home infusion therapy may not be right for everyone. Some people don’t want to see infusion supplies in their homes and refrigerators – it’s a reminder that they have a chronic health condition. Others enjoy the “me time” at the infusion clinic, where they have time to read or catch up with friends they’ve met there.

Individuals living with Fabry disease who have questions about the differences between home infusions and infusions in a clinic or hospital should always feel free to ask their healthcare provider about the advantages and disadvantages of both options. In addition, some specialty infusion pharmacies, have disease-specific advocacy teams who will walk you through the home infusion process step-by-step and answer your questions along the way.

References

Concolino, D. et al. “Home Infusion Program with Enzyme Replacement Therapy for Fabry Disease: The Experience of a Large Italian Collaborative Group.” Molecular Genetics and Metabolism Reports 12 (2017): 85-91
Milligan A, Hughes D, Goodwin S, Richfield L, Mehta A. Intravenous enzyme replacement therapy: better in home or hospital? Br J Nurs. 2006 Mar 23-Apr 12;15(6):330-3. PMID: 16628169 https://www.ncbi.nlm.nih.gov/pubmed/16628169?report=abstract
Beck M, Gaedeke J, Martus P, Karabul N, Rolfs A. [Home-based infusion therapy–a feasible approach for chronically ill patients? A new path to provide superior patient care exemplified for Fabry’s disease]. Dtsch Med Wochenschr. 2013 Nov;138(46):2345-50. doi: 10.1055/s-0033-1349624. Epub 2013 Nov 5. German. PMID: 24193859 https://www.ncbi.nlm.nih.gov/pubmed/24193859
Smid BE, Hoogendijk SL, Wijburg FA, Hollak CE, Linthorst GE. A revised home treatment algorithm for Fabry disease: influence of antibody formation. Mol Genet Metab. 2013 Feb;108(2):132-7. doi: 10.1016/j.ymgme.2012.12.005. Epub 2012 Dec 28. PMID: 23332169 https://www.ncbi.nlm.nih.gov/pubmed/23332169
Kisinovsky I, Cáceres G, Coronel C, Reisin R. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina. Medicina (B Aires). 2013;73(1):31-4.PMID: 23335703 http://www.medicinabuenosaires.com/PMID/23335703.pdf