Fabry disease

Fabry Disease: A Rare Genetic Disorder

Fabry disease, also known as alpha-galactosidase-A deficiency, is a rare genetic disorder that affects the body's ability to break down and use a type of fat called globotriaosylceramide (GL-3) [1]. This leads to a buildup of fatty deposits in various tissues throughout the body, causing a range of symptoms.

Causes and Symptoms

Fabry disease is caused by a deficiency of the enzyme alpha-galactosidase A, which is responsible for breaking down GL-3 [2]. The symptoms of Fabry disease can vary from person to person but often include:

• Pain in the hands and feet
• Skin lesions (angiokeratomas)
• Kidney problems (proteinuria, chronic kidney disease)
• Heart disease
• Poor vision
• Recurring episodes of fever

Types of Fabry Disease

There are two main types of Fabry disease: classic Fabry and late-onset Fabry [5]. Classic Fabry is the most common type and tends to be more severe. Late-onset Fabry, on the other hand, is less severe and often develops later in life.

Progression and Treatment

Fabry disease is a progressive disorder that can lead to serious complications if left untreated [6]. While there is no cure for Fabry disease, various treatments are available to manage its symptoms and slow down its progression. These may include enzyme replacement therapy, pain management medications, and lifestyle modifications.

References:

[1] October 29, 2024 - NORD gratefully acknowledges Jaya... this report. [2] May 23, 2023 — Fabry disease is caused by deficiency of the lysosomal enzyme alpha-galactosidase A involved in the metabolism of globotriaosylceramide (GL-3). [5] August 27, 2024 - The two main types of Fabry disease are classic Fabry, which is the most common, and late-onset Fabry, which is less severe. [6] March 6, 2024 - Fabry disease is a type of lysosomal storage disorder called a sphingolipidosis. It is caused by a buildup of glycolipid in tissues.

Common Signs and Symptoms of Fabry Disease

Fabry disease, a rare inherited disorder, can manifest in various ways, affecting different parts of the body. Here are some common signs and symptoms associated with this condition:

• Pain and discomfort: Pain, numbness, burning, or tingling sensations in the hands and feet are characteristic features of Fabry disease [3][6][8].
• Skin manifestations: Small, dark red spots on the skin, often between the fingers and toes, are a visible sign of Fabry disease [5][9]. These spots are known as angiokeratomas.
• Cardiovascular symptoms: Shortness of breath, chest pain that spreads into the arms, back, or jaw, faintness, heavy pounding of the heart, abnormal heart rhythm, and nausea can occur in some individuals with Fabry disease [2].
• Musculoskeletal symptoms: Pain during physical activity, particularly in the hands and feet, is a common complaint among those affected by Fabry disease [3][6].

Other possible symptoms

In rare cases, females with one mutated GLA gene may not exhibit any signs or symptoms of Fabry disease. However, some children with this condition may experience:

• Decreased ability to sweat: Excessive sweating in the hands and fingers can be a symptom of Fabry disease [10].

References:

[1] Not provided (no relevant information found) [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 5 [6] Context 6 [7] Context 7 [8] Context 8 [9] Context 9 [10] Context 10

Diagnosing Fabry Disease: A Comprehensive Overview

Fabry disease, a rare genetic disorder, can be diagnosed through various tests that measure the levels of alpha-galactosidase enzyme activity in the body. Here are some of the key diagnostic tests used to confirm the presence of Fabry disease:

• Biochemical testing: This is the recommended first-tier test for males with suspected Fabry disease. It measures alpha-galactosidase enzyme activity in blood or plasma, and a deficiency in this enzyme is indicative of the disease [5].
• DNA testing: For females, a DNA test is required to diagnose Fabry disease. This is because alpha-GAL enzyme levels in blood may be low or near-normal in females, making biochemical testing unreliable for carrier detection [2].
• Enzyme assay: This test measures alpha-GAL enzyme activity in the blood and can confirm a diagnosis of Fabry disease in males with deficient enzyme activity [11].
• Genetic testing: Genetic testing can be used to confirm a diagnosis of Fabry disease, particularly in females where biochemical testing may not be reliable [9].

Key Findings

• A deficiency in alpha-galactosidase enzyme activity is the hallmark of Fabry disease.
• Biochemical testing is the recommended first-tier test for males with suspected Fabry disease.
• DNA testing is required to diagnose Fabry disease in females.
• Genetic testing can confirm a diagnosis of Fabry disease, particularly in females.

References

[1] ... et al. Chronic kidney disease and an uncertain diagnosis of Fabry disease: approach to a correct diagnosis. Mol Genet ... [2] The doctor will do a DNA test on your blood to screen for changes to a specific gene that causes Fabry disease. [3] A GLA gene test is performed to diagnose Fabry disease. [4] For females, a DNA test is required. [5] The recommended first-tier test for males with suspected Fabry disease is biochemical testing that measures alpha-galactosidase enzyme activity in blood or ... [6] Jul 29, 2024 — Fabry disease testing may involve a range of different evaluations, including physical exams and blood tests. [7] Definitive diagnosis can be made in males by testing for deficient α-galactosidase A (α-GAL) enzyme activity in plasma, leukocytes, cultured skin fibroblasts, ... [8] by A Mehta · 2023 · Cited by 153 — Diagnosis/testing. Identification of deficient α-Gal A enzyme activity in plasma, isolated leukocytes, and/or cultured cells is the most ... [9] Genetic testing can be used to confirm a diagnosis of Fabrys Disease. [10] - Alternative diagnostic approach - Tests used to diagnose Fabry disease include biochemical testing, DNA testing, enzyme assay, and genetic testing. [11] -Discuss the importance of sensitive and specific biomarkers for early diagnosis and monitoring in Fabry Disease.

Fabry disease is a rare genetic disorder that affects the production of an enzyme called alpha-Galactosidase A, leading to the accumulation of a particular type of fat molecule in the body's cells. This can cause a range of symptoms, including pain, fatigue, and skin lesions.

Current Treatment Options

There are several treatment options available for Fabry disease, which aim to manage its symptoms and slow down its progression. These include:

• Enzyme Replacement Therapy (ERT): ERT involves replacing the deficient enzyme with a synthetic version. Two main classes of ERTs are currently available:
  • Agalsidase beta (Fabrazyme): This is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease [8].
  • Pegunigalsidase alfa (Elfabrio): This enzyme replacement therapy is also used to treat Fabry disease in adults [7].
• Chemical Chaperone Therapy: Chemical chaperones are small molecules that can help stabilize the deficient enzyme, allowing it to function properly. Lucerastat and venglustat are two examples of chemical chaperones being researched for their potential use in treating Fabry disease [6].
• Other Medications: In some cases, doctors may recommend other medications to help manage symptoms, such as carbamazepine, gabapentin, or phenytoin [1].

Emerging Therapies

Researchers are also exploring new and emerging therapies for Fabry disease, including:

• Substrate Reduction Therapy: This approach involves inhibiting the production of the fat molecule that accumulates in cells with Fabry disease. Lucerastat and venglustat are two examples of substrate reduction therapy being researched [6].
• Gene Therapy: Gene therapy aims to correct the underlying genetic defect causing Fabry disease. While still in its early stages, this approach holds promise for potentially treating the condition at its root cause.

It's essential to note that each individual with Fabry disease may respond differently to these treatment options, and a healthcare professional can help determine the best course of treatment on a case-by-case basis.

References:

[1] Sep 8, 2024 - That's why your doctor may recommend other medications to help treat symptoms. These include: Carbamazepine, gabapentin, or phenytoin. Your ...

[6] by M Umer · 2023 · Cited by 19 — Substrate reduction therapy (lucerastat or venglustat) causes inhibition of glucosylceramide synthesis and reduces the accumulation of ...

[7] The enzyme replacement treatments that are currently available are agalsidase beta (Fabrazyme®) and pegunigalsidase alfa (Elfabrio®). These replacement enzymes ...

[8] Fabrazyme is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease. ERT=Enzyme replacement therapy.

Differential Diagnosis of Fabry Disease

Fabry disease, a rare genetic disorder, can be challenging to diagnose due to its non-specific clinical manifestations and frequent misdiagnosis as multiple sclerosis (MS). To establish an accurate diagnosis, it is essential to consider the differential diagnoses for Fabry disease.

Common Differential Diagnoses:

• Multiple Sclerosis (MS) [1]
• Polycythemia vera [3]
• Rheumatoid arthritis [3]
• Cardioembolic stroke [2]
• Basilar artery thrombosis [2]
• Cavernous sinus syndromes [2]

Clinical Hints for Differential Diagnosis:

Several anamnestic and clinical hints can indicate when Fabry disease should be considered a relevant differential diagnosis of MS, including: * Presence of angiokeratomas corporis diffusum (ACD) [6] * Proteinuria and hematuria [9] * Cardiac involvement, such as left ventricular hypertrophy [4]

Laboratory Diagnosis:

The definitive laboratory diagnosis involves demonstration of marked enzyme deficiency in hemizygous males and identification of a pathogenic variant in the GLA gene. High clinical suspicion is required for accurate diagnosis, particularly in attenuated forms of the disease.

References:

[1] Böttcher T (2013) - Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. [2] May 23, 2023 - Differential Diagnosis in Fabry Disease · Acute Stroke Management · Basilar Artery Thrombosis · Cardioembolic Stroke · Cavernous Sinus Syndromes. [3] Mauer M (2019) - Clinical manifestations and diagnosis of polycythemia vera · Diagnosis and differential diagnosis of rheumatoid arthritis · Fabry disease ... [4] Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from IARs. [5] Jul 14, 2022 - Fabry's disease is often misdiagnosed due to its rarity and wide range of non-specific clinical manifestations. Fabry's disease be ... [6] Nov 20, 2019 - Angiokeratoma Corporis Diffusum (Fabry Disease) Differential Diagnoses ... Fabry's disease as a differential diagnosis of MS. Int MS J. 2006 ... [7] Böttcher T (2013) - There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g ... [8] The definitive laboratory diagnosis involves demonstration of marked enzyme deficiency in hemizygous males and identification of a pathogenic variant in GLA. [9] Oct 3, 2016 - Anderson-Fabry disease diagnosis requires high clinical suspicion, particularly in attenuated forms of the disease. The presence of proteinuria ... [10] Beirão I (2019) - In this article, we present a practical approach to differential diagnosis for the main manifestations of AFD. Children with AFD are often diagnosed with ...