Fabry Disease

Overview

Fabry disease is an X-linked, progressive, multisystem lysosomal storage disorder. It is caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in an accumulation of globotriaosylceramide (GL-3) and related glycosphingolipids and subsequently progressive impairment of normal cell function in multiple organ systems. [Germain: 2010] [Kaminsky: 2013] [National: 2012]

As an X-linked disorder, males with Fabry disease are typically more severely affected. Classically, males will present with signs/symptoms in early childhood. Early signs/symptoms include angiokeratomas, episodic acroparesthesia, sweating abnormalities, and corneal and lenticular opacities. This may then progress to typically adult-onset renal disease/failure, left ventricular hypertrophy, and cerebrovascular disease.

Though much less common, more mild forms of Fabry disease exist in which classic symptoms start in adulthood, and some individual organ systems may be significantly affected but not others. Heterozygous females present with significantly more clinical variability ranging from the complete absence of symptoms throughout life to being as severely symptomatic as males.

The current therapeutic approach involves enzyme replacement therapy (ERT). While not a cure, ERT positively impacts pain, kidney function, and possibly other organs. [El: 2016] Patients with specific genetic variants might respond to oral chaperone therapy with migalastat. [Feldt-Rasmussen: 2020] Clinical trials are ongoing for developing additional therapeutic approaches.

Other Names & Coding

Alpha-galactosidase A deficiency
Anderson-Fabry disease
Angiokeratoma corporis diffusum
GLA deficiency
ICD-10 coding

E75.21, Fabry (-Anderson) disease

Prevalence

Though initially estimated to affect 1:50,000 males [National: 2012], more recent studies involving newborn screening suggest an incidence as high as 1:3100 to 1:3277. [Spada: 2006] [Hopkins: 2018]

Genetics

Fabry disease is inherited in an X-linked pattern and caused by mutations in the GLA gene located in Xq22.1. [Pinto: 2010] More than 670 different mutations that cause Fabry disease have been identified, including missense, nonsense, splicing, and variants caused by other types of rearrangements without any specific “hot spots” in the gene. [Smid: 2014] [Gal: 2006] Mutations that result in <1% residual α-galactosidase A activity usually lead to more severe disease with earlier onset and more significant symptom burden, corresponding with the “classic” phenotype. [Hsu: 2018] [Sigmundsdottir: 2014] Mutations with >1% α-galactosidase A activity result in a wider spectrum of symptoms including later onset and organ-specific symptoms.

Notably, heterozygous females may not just be carriers; the majority will experience some symptoms of Fabry, though typically less severe than their male counterparts.

Due to the X-linked inheritance, women who have a Fabry-associated gene variant have a 50% chance of passing the gene to their child regardless of sex, while men with the Fabry disease will pass it to all of their daughters only. In 1-2% of patients, a Fabry-associated gene mutation is de novo (i.e., not inherited from a parent). [Sestito: 2013] An individual with a de novo mutation will still pass the condition on in an X-linked inheritance pattern.

Prognosis

The prognosis of Fabry disease is largely dependent upon access to medical care and proper treatment. Nonetheless, data from the Fabry Registry report a decreased life expectancy with an average of 58.2 years for men (vs. 74.7 in the general population) and 75.4 years for women (vs. 80.0 in the general population). [Waldek: 2009] Cardiovascular remains the most common cause of death among men and women with Fabry disease, particularly among those who had previously required renal replacement therapy. [Waldek: 2009] However, most of the data are based on patients with Fabry disease diagnosed much later in life and did not have access to new treatments when they were younger. Therefore, life expectancy and quality of life are expected to improve over time.

Practice Guidelines

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.
Fabry disease revisited: Management and treatment recommendations for adult patients.
Mol Genet Metab. 2018;123(4):416-427. PubMed abstract

Laney DA, Bennett RL, Clarke V, Fox A, Hopkin RJ, Johnson J, O'Rourke E, Sims K, Walter G.
Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors.
J Genet Couns. 2013;22(5):555-64. PubMed abstract

Roles of the Medical Home

In addition to well-child and acute-care visits, primary care clinicians fulfill a crucial role for the child and family by:
  • Providing education and support
  • Identifying sources of information and other needed resources
  • Monitoring for disease symptoms control
  • Coordinating care with subspecialists
  • Advocating for needed accommodations at school/work

Clinical Assessment

Overview

Because the manifestations of Fabry disease and organ involvement do not progress in a fixed order, all relevant organ systems need to be assessed, treated, and monitored. [Eng: 2006] The primary care clinician should work with the metabolic team to determine an assessment plan. A schedule of recommended testing at various ages can be found in the Fabry Registry Recommended Schedule of Assessments (PDF Document 258 KB).

Pearls & Alerts for Assessment

Genetic analysis is necessary to confirm a diagnosis in females

Females with Fabry disease may have normal α-galactosidase enzyme activity and GL-3 levels, so a GLA genetic analysis should be used to confirm diagnosis. [Mehta: 2010]

Females who have the Fabry gene are often symptomatic

Despite the X-linked inheritance pattern, approximately 70% of women are not simply "carriers" of Fabry but are also symptomatic. Females should be assessed regularly for disease progression.

Screening

For the Condition

Fabry Disease for Fabry disease is not performed in all states. Some of the patients identified by newborn screening have very mild mutations that might not result in symptoms or may represent “late-onset” phenotypes. [Hsu: 2018]

In states without newborn screening, children with a family history of Fabry and those with corneal whorling (cornea verticillata) found on a slit lamp eye exam should be tested as these are very specific findings. [Laney: 2013] Testing may also be warranted in persons with 2 or more of the following symptoms:
  1. Vascular cutaneous lesions (angiokeratomas)
  2. Sweating abnormalities (anhidrosis, hypohidrosis, and rarely hyperhidrosis)
  3. Personal or family history of:
    • Periodic crises of severe pain in the hands/feet (acroparesthesia)
    • Unexplained renal failure
    • Unexplained stroke
Consultation with a genetic metabolic specialist (see Biochemical Genetics (Metabolics) (see NM providers [1])) and a genetic counselor (see Genetic Testing and Counseling (see NM providers [7])) is recommended for diagnosis. The Fabry Disease: Testing Algorithm (Mayo Clinic) (PDF Document 496 KB) describes appropriate screening and testing for Fabry disease based on indications and gender of the child

Of Family Members

The metabolic geneticist or a genetic counselor will make screening recommendations based on inheritance risk. Parents of children diagnosed with Fabry should understand the options for future pregnancies and risks of Fabry being inherited.

For Complications

Reports of depression are found in 45-58% of individuals with Fabry, with 39% also reporting anxiety. [Laney: 2013] Panic attacks and ADHD can manifest at any age. [Sestito: 2013] Screening with validated tools is recommended. These Portal modules offer detail on screening tools:

Presentations

Classically presenting males typically have <1% residual α-galactosidase A activity and therefore follow a common clinical course. [Hsu: 2018] [Sigmundsdottir: 2014] Angiokeratomas may be the earliest sign of Fabry disease (66% of males and 33% of females), presenting as a cluster of dark red/blue non-blanching papules often localized to the umbilicus, pelvic region, buttocks, and upper thighs. [Orteu: 2007] Episodic acroparesthesia also tends to start in early childhood with intermittent crises of severe burning pain in the hands and feet, often triggered by exercise, fatigue, emotional stress, or rapid temperature changes. Corneal verticillate and lenticular changes are common and considered nearly pathognomonic for Fabry disease when seen. [Sestito: 2013]

The disease will eventually progress, and during adolescence/adulthood, patients may experience heart, kidney, and central nervous system problems. [Mehta: 2010] [Sestito: 2013] [Löhle: 2015] Cardiac disease may include mitral insufficiency, conduction abnormalities, left ventricular enlargement, and hypertrophic cardiomyopathy. Renal disease typically starts with proteinuria followed by azotemia and gradual deterioration of renal function in the 3rd to 5th decade of life. Cerebrovascular disease caused by small vessel involvement may lead to transient ischemic attacks, aneurysms, seizures, and cerebral strokes resulting in permanent neurological damage. Less common features include chronic gastrointestinal symptoms like diarrhea, nausea/vomiting, and abdominal pain, pulmonary disease, hearing loss, tinnitus, and psychological disease like depression and anxiety that may be secondary to the chronic nature of the other symptoms. All relevant organ systems need to be assessed, treated, and monitored. [Eng: 2006]

Males with >1% α-galactosidase A activity tend to present on a wider spectrum ranging from “classic” phenotype to organ-specific symptoms such as adult-onset involvement of the heart or kidneys only.

Females should be assessed regularly for symptom manifestations; 70% of women exhibit symptoms and are not simply “carriers.” The symptoms can occur with greater variability than in males. Some women may remain asymptomatic and, therefore, not require treatment.

Diagnostic Criteria

  • Males:
    • Molecular identification of hemizygous pathogenic variant in the GLA gene
    • Reduced plasma α-galactosidase enzyme activity
    • Elevated plasma or urinary GL-3
  • Females:
    • Molecular identification of heterozygous pathogenic variant in the GLA gene

Differential Diagnosis

Differential diagnoses include:
  • Fibromyalgia
  • Rheumatic fever
  • Multiple sclerosis
  • Raynaud syndrome

Comorbid & Secondary Conditions

Possible pediatric comorbidities by organ system include: [Mehta: 2010] [Sestito: 2013] [Löhle: 2015]
  • Ocular: Cornea verticillata (corneal whorling), lenticular changes, subcapsular cataracts
  • Cerebrovascular: Transient ischemic attack (TIA), stroke, subclinical white matter lesions
  • Cardiac: Arrhythmia, left ventricular hypertrophy, myocardial infarction
  • Renal: Proteinuria, azotemia, reduced GFR, end-stage renal disease
  • Gastrointestinal: Abdominal pain, diarrhea, constipation, nausea, vomiting, anorexia
  • Neurological: Neuropathic pain, acroparesthesia, tinnitus, sensorineural hearing loss, vertigo
  • Psychosocial: Depression, anxiety, panic attacks, ADHD
  • Integumentary: Angiokeratomas, anhydrosis or hypohydrosis, telangiectasia
  • Other: Priapism

History & Examination

Current & Past Medical History

The initial assessment may elicit a personal history of pain in the hands and feet during childhood that may have been diagnosed as “growing pains.” A history of chronic gastrointestinal complaints without an identifiable cause despite thorough workup may also be reported. [Sestito: 2013]

Family History

Ask about family history of: [Sestito: 2013]
  • Unexplained, early deaths due to renal failure
  • Cardiac disease
  • Stroke
  • Hypohydrosis
  • Episodic burning pain in the hands and feet
  • Chronic unexplained gastrointestinal disturbances
The absence of a family history of the disease or family members with symptoms does not rule out a diagnosis since Fabry may be passed on through several generations by unidentified affected females with non-classic symptoms. Additionally, cases of de novo variants have been reported as well.

Physical Exam

Skin

Examine children for angiokeratomas, usually found in the “bathing suit” area (for images, see Angiokeratomas.)

HEENT/Oral

Cornea verticillate (corneal whirling) can be found
on slit lamp eye exams in 70% of females and most males
with Fabry disease . [Sestito: 2013] Lenticular changes, including
subcapsular deposits (Fabry” cataracts), also can be found.
Notably, neither the corneal or lenticular changes interfere with visual acuity.

Photo, right: cornea verticillata / [Burlina: 2011]
Eye showing Cornea whorling

Heart

Sinus bradycardia and systolic murmurs may be early signs of cardiac involvement. [Sestito: 2013] Cardiac abnormalities, such as left ventricular hypertrophy, arrhythmias, and valvular insufficiency, can occur in children and adults with Fabry disease.

Testing

Sensory Testing

  • An audiologic evaluation every 2-3 years
  • Slit-lamp ophthalmology exam should be performed at time of diagnosis and as needed thereafter.

Laboratory Testing

Routine monitoring labs may include:
  • Glomerular filtration rate, albuminuria/proteinuria, creatinine, BUN
  • Enzyme replacement therapy status (GL-3, antibody testing)

Imaging

  • EKG and echocardiogram every 2-3 years in children and yearly for adults, unless otherwise indicated
  • Cranial MRI every 2-3 years, unless otherwise indicated

Genetic Testing

Genetic testing of the GLA gene performed as part of diagnosis

Specialty Collaborations & Other Services

Biochemical Genetics (Metabolics) (see NM providers [1])

All children diagnosed with Fabry should be followed by a genetic/metabolic specialist familiar with monitoring and treating the disease and who can help provide education and support to the family.

Pediatric Cardiology (see NM providers [1])

Refer for initial symptoms of early cardiac involvement, such as new-onset murmurs or bradycardia.

Pediatric Nephrology (see NM providers [0])

Refer those with proteinuria or microalbuminuria for more extensive testing to determine renal involvement.

Pediatric Gastroenterology (see NM providers [1])

Referral may be helpful for the management of chronic gastrointestinal disturbances, including constipation, diarrhea, abdominal pain, nausea, and vomiting.

General Counseling Services (see NM providers [41])

Children and adolescents who present with symptoms of depression or anxiety may benefit from referral.

Treatment & Management

Overview

With treatment, disease progression can be slowed, though some degree of persistent symptoms can be expected despite available treatments. Enzyme replacement therapy (ERT) with agalsidase beta (Fabrazyme) is an FDA-approved treatment for Fabry disease in the United States. ERT, given by infusion every 2 weeks for the duration of the patient's life, has been shown to slow the progression of renal and cardiac disease as well as help with pain and other symptoms. [Sestito: 2013] [Germain: 2015] [El: 2016] In some cases, patients may qualify for oral chaperone therapy with Migalastat depending on their specific gene variant. There are also a number of other new therapeutics under investigation with clinical trial results pending. In addition to ERT, symptom management is a key component of managing Fabry disease.

Pearls & Alerts for Treatment & Management

Minimize pain triggers

Exercise, fatigue, emotional stress, or rapid temperature changes may trigger episodes of pain.

Systems

Neurology

Neural damage from GL-3 accumulation causes dysfunction of the small nerve fibers in the peripheral somatic and autonomic nervous systems. [Eng: 2006] [Sestito: 2013] The earliest symptoms in children usually include chronic acroparesthesias (burning or tingling pain in the extremities). Children with Fabry may also experience acute pain episodes termed “Fabry crises,” which begin in the feet and hands and radiate proximally. Episodes may last minutes to days. With the “classical” phenotype, these episodes may begin as early as 4 years, with a mean onset of 10 years. The episodes tend to present later, if at all, in females. The extent of pain can be debilitating and contribute to depression, illicit drug use, and suicidality in some patients, particularly among those without a diagnosis. Chronic and difficult to manage symptoms can also impact school attendance, performance, and ability to participate in sports. [Laney: 2013] [Sestito: 2013]

Management of neuropathic pain consists of avoidance of triggers and over-the-counter analgesics. If still unable to control the neuropathic pain, additional medications such as gabapentin, carbamazepine, or phenytoin may be indicated.

Specialty Collaborations & Other Services

Pediatric Neurology (see NM providers [0])

Refer if the child's neuropathic pain is difficult to manage.

Renal

The accumulation of GL-3 in the kidney leads to irreversible damage to the function of the glomerular barrier. [Sestito: 2013] Proteinuria and decreased GFR can typically be found before symptoms of renal impairment appear. Notably, ERT is not as effective in slowing the progression of the disease, particularly after a patient is exhibiting >1 g/day of proteinuria and/or GFR<60 ml/min. [Najafian: 2013] Screening is necessary as therapies like ACE inhibitors/ARBs may help minimize renal disease. [Tahir: 2007] Advance stages may require renal replacement therapy and, in some cases, a kidney transplant

Specialty Collaborations & Other Services

Pediatric Nephrology (see NM providers [0])

Refer for treatment and management if there is any kidney involvement.

Cardiology

Fabry disease patients may manifest sinus bradycardia, systolic murmurs, chest pain, dyspnea, arrhythmias, left ventricular hypertrophy, palpitations, and syncope as early signs of cardiac involvement. [Sestito: 2013] Cardiac hypertrophy of Fabry disease may respond to ERT, though the benefit on conduction defects remains unknown. [Mehta: 2010] Management includes periodic cardiac imagining and monitoring for bradycardia and arrhythmias via a Holter monitor.

Specialty Collaborations & Other Services

Pediatric Cardiology (see NM providers [1])

Refer children with any early signs of cardiac involvement.

Gastro-Intestinal & Bowel Function

Gastrointestinal symptoms can be much more variable with any combination of chronic abdominal pain, diarrhea, constipation, nausea, vomiting, and bloating, which may, over time, lead to anorexia and difficulty gaining weight. [Sestito: 2013] Gastrointestinal symptoms may respond to treatment with H2 blockers and/or metoclopramide.

Specialty Collaborations & Other Services

Pediatric Gastroenterology (see NM providers [1])

Refer any patient whose gastrointestinal symptoms are difficult to manage with conventional therapies.

Skin & Appearance

Angiokeratomas are common, particularly in males, and often localized to the umbilicus, pelvic region, buttocks, and upper thighs. [Orteu: 2007] [Sestito: 2013] The lesions typically increase in number and size into adolescence but are benign and do not require treatment.

Specialty Collaborations & Other Services

Pediatric Dermatology (see NM providers [1])

Refer children who may find the lesions cosmetically unappealing to a dermatologist.

Ears/Hearing

Tinnitus and hearing loss have been reported and may necessitate hearing aids.

Specialty Collaborations & Other Services

Audiology (see NM providers [8])

Refer for help managing tinnitus or hearing loss.

Mental Health/Behavior

Children and adolescents report a significant negative impact on quality of life with Fabry disease. [Sestito: 2013] [Arends: 2015] Some adolescents self-medicate to alleviate pain, which could lead to drug abuse. Additionally, there is an increased risk of depression and anxiety. [Eng: 2006] [Löhle: 2015] There are no specific guidelines for the management of mental health disorders in Fabry disease. Therefore, referral to appropriate professionals such as psychiatrists, counselors, pain centers, or social workers with general psychiatric treatments. For management information, see:

Specialty Collaborations & Other Services

General Counseling Services (see NM providers [41])

This category includes all types of counselors/counseling for patients. Once on the page, the search can be narrowed by city or search within this Category field.

Pain Management (see NM providers [1])

A Physical Medicine and Rehabilitation or a Pain Clinic (if available locally) referral may be helpful for managing pain.

Ask the Specialist

I am treating a child with Fabry that complains of frequent pain. On exam, I cannot find anything that would explain these symptoms. Are they really having this much pain?

Yes. The pain in Fabry disease is real and needs to be treated. Chronic, frequent pain may need treatment with neuropathic pain medications, such as Neurontin or Carbamazepine. Episodic intense periods of pain, often called “Fabry crisis” may need to be treated with stronger pain-relieving medications.

When should enzyme replacement therapy (ERT) begin?

There is no consensus on when to start treatment with ERT; the decisions should be discussed with a metabolic specialist. Several studies have suggested that treatment should begin before critical organ changes have occurred. [Sestito: 2013] Assessment and vigilant monitoring for early symptoms and collaboration with a metabolic geneticist are vital. Studies show ERT is less effective if started after a patient is exhibiting >1 g/day of proteinuria and/or GFR<60 ml/min.

Resources for Clinicians

Fabry Disease provides guidance for primary care clinicians receiving a positive newborn screen result.

On the Web

Fabry for Healthcare Professionals (Genzyme)
Diagnosis, genetics, and management information, patient education, publications, and other resources for clinicians.

Fabry Disease (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

Fabry Disease (NORD)
Information for families includes synonyms, signs & symptoms, causes, affected populations, related disorders, diagnosis, therapies (both standard and investigational), and support organizations; National Organization of Rare Disorders.

Helpful Articles

PubMed search for articles over the last 2 years about Fabry disease in children

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.
Genet Med. 2015;17(5):323-30. PubMed abstract

Sestito S, Ceravolo F, Concolino D.
Anderson-Fabry disease in children.
Curr Pharm Des. 2013;19(33):6037-45. PubMed abstract

Thomas AS, Hughes DA.
Fabry disease.
Pediatr Endocrinol Rev. 2014;12 Suppl 1:88-101. PubMed abstract

Toyooka K.
Fabry disease.
Handb Clin Neurol. 2013;115:629-42. PubMed abstract

Clinical Tools

Care Processes & Protocols

Fabry Disease: Testing Algorithm (Mayo Clinic) (PDF Document 496 KB)
Describes appropriate screening and testing based on indications and gender.

Fabry: Response to Positive Newborn Screen (Mayo Clinic) (PDF Document 476 KB)
One-page algorithm for clinicians; Mayo Medical Laboratories.

Patient Education & Instructions

Fabry Disease: Guide for the Newly Diagnosed (Emory University) (PDF Document 141 KB)
Factsheet with information about the Fabry symptoms, treatment, tests, and resources.

A Guide for Women Living with Fabry Disease (Genzyme) (PDF Document 1.1 MB)
Explains the researched-based signs and symptoms that women with Fabry disease may experience.

Resources for Patients & Families

Information on the Web

Fabry Disease (NINDS)
Information about Fabry disease, treatment, prognosis, research, and links to other organizations; National Institute of Neurological Disorders and Stroke.

GLA Gene (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Fabry Inheritance Patterns (Genzyme)
Explains how to create a medical family tree to understand the inheritance pattern and risk of passing on Fabry disease.

How Do I Talk To My Family About Fabry? (Genetic Alliance and Genzyme) (PDF Document 5.2 MB)
Thirty-four pages of information about Fabry disease include how it is passed on, a family tree, how to talk to other family members, family stories, and resources.

How Do I Talk To My Family About Fabry? (Genetic Alliance and Genzyme, Spanish) (PDF Document 6.3 MB)
Thirty-four pages of information about Fabry disease in Spanish include how it is passed on, a family tree, talking to other family members, family stories, and resources.

Discover Fabry (Genzyme)
Diagnosis, management, resources, and support information for families affected by Fabry disease.

National & Local Support

Fabry Support & Information Group (FSIG)
Access to support groups, discussion forums, resources, and research related to Fabry disease.

National Fabry Disease Foundation
Information about Fabry disease, counseling, finding a physician, and the Charles Kleinschmidt Fabry Family Weekend Camp.

Studies/Registries

Fabry Registry (Genzyme)
Any person with a confirmed diagnosis of Fabry disease is eligible to participate regardless of disease type, treatment status, or treatment choice.

Clinical Trials in Fabry (clinicaltrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Services for Patients & Families in New Mexico (NM)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Authors & Reviewers

Initial publication: June 2015; last update/revision: February 2022
Current Authors and Reviewers:
Author: Michael Angerbauer
Senior Author: Brian J. Shayota, MD, MPH
Authoring history
2017: update: Susan Jensen, DNPA; Dawn LaneyCA
2015: update: Meghan Candee, MDA
2015: first version: Nicola Longo, MD, Ph.D.R
AAuthor; CAContributing Author; SASenior Author; RReviewer

Bibliography

Arends M, Hollak CE, Biegstraaten M.
Quality of life in patients with Fabry disease: a systematic review of the literature.
Orphanet J Rare Dis. 2015;10(1):77. PubMed abstract / Full Text

Burlina AP, Sims KB, Politei JM, Bennett GJ, Baron R, Sommer C, Møller AT, Hilz MJ.
Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel.
BMC Neurol. 2011;11:61. PubMed abstract / Full Text

El Dib R, Gomaa H, Carvalho RP, Camargo SE, Bazan R, Barretti P, Barreto FC.
Enzyme replacement therapy for Anderson-Fabry disease.
Cochrane Database Syst Rev. 2016;7:CD006663. PubMed abstract / Full Text

Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, Bultas J, Lee P, Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR.
Fabry disease: guidelines for the evaluation and management of multi-organ system involvement.
Genet Med. 2006;8(9):539-48. PubMed abstract
An international panel of physicians with expertise in Fabry disease has proposed guidelines for the recognition, evaluation, and surveillance of disease-associated morbidities, as well as therapeutic strategies.

Feldt-Rasmussen U, Hughes D, Sunder-Plassmann G, Shankar S, Nedd K, Olivotto I, Ortiz D, Ohashi T, Hamazaki T, Skuban N, Yu J, Barth JA, Nicholls K.
Long-term efficacy and safety of migalastat treatment in Fabry disease: 30-month results from the open-label extension of the randomized, phase 3 ATTRACT study.
Mol Genet Metab. 2020;131(1-2):219-228. PubMed abstract

Gal A, Schäfer E, Rohard I.
The genetic basis of Fabry disease.
Oxford PharmaGenesis. 2006. PubMed abstract
Chapter 33. Available from: https://www.ncbi.nlm.nih.gov/books/NBK11574/

Germain DP.
Fabry disease.
Orphanet J Rare Dis. 2010;5:30. PubMed abstract / Full Text

Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, Lemay R, Linthorst GE, Packman S, Scott CR, Waldek S, Warnock DG, Weinreb NJ, Wilcox WR.
Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease.
J Med Genet. 2015;52(5):353-8. PubMed abstract / Full Text

Hopkins PV, Klug T, Vermette L, Raburn-Miller J, Kiesling J, Rogers S.
Incidence of 4 Lysosomal Storage Disorders From 4 Years of Newborn Screening.
JAMA Pediatr. 2018;172(7):696-697. PubMed abstract / Full Text

Hsu TR, Niu DM.
Fabry disease: Review and experience during newborn screening.
Trends Cardiovasc Med. 2018;28(4):274-281. PubMed abstract

Kaminsky P, Noel E, Jaussaud R, Leguy-Seguin V, Hachulla E, Zenone T, Lavigne C, Marie I, Maillot F, Masseau A, Serratrice C, Lidove O.
Multidimensional analysis of clinical symptoms in patients with Fabry's disease.
Int J Clin Pract. 2013;67(2):120-7. PubMed abstract

Laney DA, Bennett RL, Clarke V, Fox A, Hopkin RJ, Johnson J, O'Rourke E, Sims K, Walter G.
Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors.
J Genet Couns. 2013;22(5):555-64. PubMed abstract

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.
Genet Med. 2015;17(5):323-30. PubMed abstract

Löhle M, Hughes D, Milligan A, Richfield L, Reichmann H, Mehta A, Schapira AH.
Clinical prodromes of neurodegeneration in Anderson-Fabry disease.
Neurology. 2015;84(14):1454-64. PubMed abstract / Full Text

Mehta A, Beck M, Eyskens F, Feliciani C, Kantola I, Ramaswami U, Rolfs A, Rivera A, Waldek S, Germain DP.
Fabry disease: a review of current management strategies.
QJM. 2010;103(9):641-59. PubMed abstract / Full Text

Najafian B, Mauer M, Hopkin RJ, Svarstad E.
Renal complications of Fabry disease in children.
Pediatr Nephrol. 2013;28(5):679-87. PubMed abstract / Full Text

National Library of Medicine.
Fabry Disease.
MedlinePlus Genetics; (2012) https://medlineplus.gov/genetics/condition/fabry-disease/#frequency. Accessed on 5/17/21.

Orteu CH, Jansen T, Lidove O, Jaussaud R, Hughes DA, Pintos-Morell G, Ramaswami U, Parini R, Sunder-Plassman G, Beck M, Mehta AB.
Fabry disease and the skin: data from FOS, the Fabry outcome survey.
Br J Dermatol. 2007;157(2):331-7. PubMed abstract

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.
Fabry disease revisited: Management and treatment recommendations for adult patients.
Mol Genet Metab. 2018;123(4):416-427. PubMed abstract

Pinto LL, Vieira TA, Giugliani R, Schwartz IV.
Expression of the disease on female carriers of X-linked lysosomal disorders: a brief review.
Orphanet J Rare Dis. 2010;5:14. PubMed abstract / Full Text

Sestito S, Ceravolo F, Concolino D.
Anderson-Fabry disease in children.
Curr Pharm Des. 2013;19(33):6037-45. PubMed abstract

Sigmundsdottir L, Tchan MC, Knopman AA, Menzies GC, Batchelor J, Sillence DO.
Cognitive and psychological functioning in Fabry disease.
Arch Clin Neuropsychol. 2014;29(7):642-50. PubMed abstract / Full Text

Smid BE, van der Tol L, Cecchi F, Elliott PM, Hughes DA, Linthorst GE, Timmermans J, Weidemann F, West ML, Biegstraaten M, Lekanne Deprez RH, Florquin S, Postema PG, Tomberli B, van der Wal AC, van den Bergh Weerman MA, Hollak CE.
Uncertain diagnosis of Fabry disease: consensus recommendation on diagnosis in adults with left ventricular hypertrophy and genetic variants of unknown significance.
Int J Cardiol. 2014;177(2):400-8. PubMed abstract

Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H, Ponzone A, Desnick RJ.
High incidence of later-onset Fabry disease revealed by newborn screening.
Am J Hum Genet. 2006;79(1):31-40. PubMed abstract / Full Text

Tahir H, Jackson LL, Warnock DG.
Antiproteinuric therapy and fabry nephropathy: sustained reduction of proteinuria in patients receiving enzyme replacement therapy with agalsidase-beta.
J Am Soc Nephrol. 2007;18(9):2609-17. PubMed abstract

Thomas AS, Hughes DA.
Fabry disease.
Pediatr Endocrinol Rev. 2014;12 Suppl 1:88-101. PubMed abstract

Toyooka K.
Fabry disease.
Handb Clin Neurol. 2013;115:629-42. PubMed abstract

Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P.
Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry.
Genet Med. 2009;11(11):790-6. PubMed abstract