Patient Advocacy

General Disease Information

Fabry Disease

Fabry disease is an X-linked disease caused by mutations in the GLA gene, which encodes the alpha-Gal A enzyme. These mutations can cause alpha-Gal A, to be either absent or deficient. When alpha-Gal A is absent or deficient the substrate, GL-3 and lyso-Gb 3 accumulate, leading to damage of cells within affected parts of the individual's body and causing the various pathologies seen in Fabry disease. Fabry disease leads to progressive, irreversible organ damage, typically involving the nervous, cardiac, and renal systems, as well as multiple other tissues. The symptoms can be severe, differ from patient to patient, and begin at an early age, resulting in significant clinical, humanistic, and healthcare costs. Fabry disease requires lifelong medical intervention to manage the complications of this devastating disease across multiple organ systems.

People with Fabry disease are generally categorized in a spectrum of disease severity from a classic onset form to a more attenuated, late-onset onset form of the disease. Heterozygous females can experience a variable presentation, ranging from asymptomatic or mild symptoms to symptoms that are just as severe as those experienced by male patients. All Fabry disease is progressive and leads to organ damage regardless of the time of symptom onset.

People with Fabry disease may experience severe symptoms, or seemingly none at all, with a variety of clinical presentations in between. But even when disease presentation is asymptomatic or mild, disease substrate can accumulate, contributing to long-term damage of organs and tissues. Organ damage in Fabry disease is caused by the accumulation of GL-3 and lyso-Gb3 in the cells, leading to dysfunction in affected cells. These deposits can potentially affect multiple cell types, including:

  • Endothelial cells: vascular and neurovascular
  • Cardiomyocytes
  • Smooth muscle cells
  • Neurons within the central and peripheral nervous systems
  • Eccrine sweat glands
  • Epithelial cells: cornea, lens, airway
  • Perithelial cells: small intestine, colon, and rectum
  • Ganglion cells

Individuals with Fabry disease may experience a shorter lifespan compared with the general population. Lifespans for people with Fabry disease may be shortened to approximately 50 years for men and 70 for women — a 20- and 10-year reduction, respectively. Cardiovascular disease is the most common cause of death for both men and women.

With more than 800 known mutations of the GLA gene, there is no single genotypic cause of Fabry disease. A variety of mutation types can give rise to Fabry disease, such as missense mutations, splicing mutations, small deletions and insertions, and large deletions. Many genetic mutations are specific to individual families affected by Fabry disease, whereas some are more widespread.

It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide.

To learn more about Fabry disease and its symptoms, inheritance, and multisystemic impact, please visit FabryFacts.com, an online resource developed by Amicus Therapeutics.

Epidermolysis Bullosa

Epidermolysis Bullosa (EB) is a rare genetic disorder that manifests as blistering or erosion of the skin, and, in some cases, the epithelial lining of other organs. EB is chronic and can potentially be disfiguring and fatal. Patients with EB have painful wounds and blisters that can lead to infection and scarring. There are many genetic and symptomatic variations of EB, but all forms share the common symptom of fragile skin that blisters and tears from even the slightest friction or trauma. There are currently no approved treatments for EB. The current standard of care consists of pain management as well as bandaging and cleaning of open wounds to prevent infection. According to third-party market research, there are approximately 30,000-40,000 people diagnosed with EB in major countries (the U.S., Germany, France, England, and Japan).

Inherited EB encompasses more than 30 phenotypically or genotypically distinct entities, which share as a common feature mechanical fragility of epithelial lined or surfaced tissues, most notably the skin. A characteristic feature of all types of EB is the presence of recurrent blistering or erosions, which is the result of even minor friction.

There are four types of genetically inherited EB:

  • Simplex (EBS)
  • Dystrophic (DEB)
  • Junctional (JEB)
  • Kindler (an extremely rare form of EB)

These four types of EB are similar phenotypically (that is, in what their physical manifestations look like), but differ genotypically (in their genetic makeup) as well as in the area of the skin where there is blistering, otherwise known as "the site of ultra-structural disruption or cleavage." There is also a rare autoimmune form of the disorder called EB acquisita.

In the more severe forms of the disease, blistering can lead to deformities such as fusion of the fingers and toes, secondary skin infections, sepsis, and even death. EB may also affect the mouth and esophagus, leading to eating and swallowing problems. Serious complications, including squamous cell carcinoma, may occur in EB patients who survive childhood, which results in a high rate of mortality.

EBS accounts for the majority of these cases, with DEB the next most common form. JEB is less prevalent and Kindler is the rarest of the four. These major types are defined by the precise ultra-structural level of the skin, which splits and blisters.

Pompe Disease

Pompe disease is a Lysosomal Storage Disorder (LSD) that results from a deficiency in an enzyme, GAA. Signs and symptoms of Pompe disease can be severe and debilitating and include progressive muscle weakness throughout the body, particularly the heart and skeletal muscles. This leads to accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. Pompe disease ranges from a rapidly fatal infantile form with severe cardiac involvement to a more slowly progressive, late-onset form primarily affecting skeletal muscle. All forms are characterized by severe muscle weakness that worsens over time. In the early-onset form, patients are usually diagnosed shortly after birth and often experience enlargement of the heart and severe muscle weakness. In late-onset Pompe disease, symptoms may not appear until late childhood or adulthood and patients often experience progressive muscle weakness. It is estimated that Pompe disease affects approximately 5,000 to 10,000 people worldwide.

For more information, download our Pompe disease infographic.

CDKL5 Deficiency: General Disease Information

CDKL5 (cyclin-dependent kinase-like 5) is a gene on the X-chromosome encoding the CDKL5 protein that regulates the expression of several essential proteins for normal brain development. Genetic mutations in the CDKL5 gene result in CDKL5 protein deficiency and the disorder manifests clinically as persistent seizures starting in infancy, followed by severe impairment in neurological development. Most children affected by CDKL5 deficiency cannot walk or care for themselves and may also suffer from scoliosis, visual impairment, sensory issues, and gastrointestinal complications.

CDKL5 mutations have been found in children diagnosed with cerebral palsy and autism, among other conditions, and the disorder was previously classified as atypical Rett Syndrome, an early seizure variant of Rett Syndrome. There are more than 1,200 documented cases of CDKL5 deficiency worldwide, with the number of identified patients increasing as genetic testing for the disorder becomes more common.1

   1Louloufoundation.org