Fabry Disease
Description
Introduction
A uncommon, multi-systemic X-linked lysosomal storage illness, Fabry disease is brought on by α-galactosidase A (α-Gal A) deficiency.
causes globotriaosylceramide (Gb3/GL-3) to build up in lysosomes.
Angiokeratoma corporis diffusum is a classic skin condition that is frequently associated with renal illness (proteinuria).
Skin, eyes, kidneys, heart, brain, and peripheral nervous system are among the many systems involved.
Suspect in young individuals with renal impairment, MI, and stroke.
Etiology
Cause: 1000 mutations (nonsense, missense, frameshift, and splicing) were found in the X chromosome's GLA gene, which resulted in a defective α-Gal A.
Pathogenesis: Endothelial oedema, vascular proliferation, and progressive Gb3 buildup lead to multi-organ dysfunction.
Severe, multi-organ, early onset is the classic phenotype.
Variants with a later onset: Usually milder and cardiac-restricted (missense mutations).
Epidemiology
In white males, the prevalence ranges from 1:17,000 to 1:117,000.
Males with classic mutations range from 1:22,000 to 1:40,000.
Atypical and later-onset variations: 1:6000–1:40,000 for females and up to 1:1000–1:3000 for men.
All races and ethnicities are affected, however they are frequently underdiagnosed.
Pathophysiology
Gb3 breakdown is impeded by α-Gal A deficiency, which leads to lysosomal buildup.
skin, kidneys (glomeruli/tubules), heart, central nervous system, peripheral nervous system, and cornea.
Vascular pathology includes ischaemia, infarction, endothelial growth, and vascular obstruction.
Neurological: prothrombotic condition (↓thrombomodulin, ↑PAI) and aberrant NO/eNOS activity cause strokes in young people.
Renal: development of renal sinus cysts, proteinuria, polyuria, and end-stage renal disease.
Heart: valvular disorders, arrhythmias, conduction abnormalities, and hypertrophy.
Histopathology
Skin biopsy: dermal lipid buildup.
"Zebra bodies" (concentric lamellar myelin-like inclusions) in renal biopsy (EM)
Background and Clinical Characteristics
Acroparesthesias, or searing pain in the extremities, are painful throughout childhood and early adolescence.
Anhidrosis or hypohidrosis.
sensitivity for heat.
gastrointestinal problems (diarrhoea, cramps).
Angiokeratomas of the skin (umbilical/groin).
Eye: lenticular opacities, corneal verticillata.
Progressive illness: renal: proteinuria, polyuria → end-stage renal disease.
Heart: valvular disorders, arrhythmias, and LVH.
Neurological: vertigo, hearing loss, and CVA (ischaemic stroke).
Other: exercise intolerance, cold intolerance, and lymphadenopathy.
Evaluation
Suspicion: X-linked family history and multisystem illness.
Labs/Investigations: Leukocyte/plasma α-Gal A activity (perhaps normal in females, diagnostic in males).
genetic analysis (mutations in GLA).
Oval fat bodies in urine.
Renal biopsy: Zebra bodies and Gb3 deposits.
Cardiac: ECG, echo (conduction faults, hypertrophy).
Neuro: MRI/MRA (small vessel ischaemia, vertebrobasilar dilatation).
Complications
angiokeratomas.
acroparesthesias.
End-stage renal disease (ESRD).
arrhythmias, valvular disorders, and cardiomegaly.
hearing loss, vertigo, TIAs, and stroke.
corneal verticillata and opacities of the lenses.
Protocol
Management and Treatment
The aim is to delay the development; there is no cure.
Treatment with Enzyme Replacement (ERT):
IV injection of agalsidase α or β every two weeks.
Every guy impacted, regardless of symptoms.
carriers or females only if there is organ involvement.
Continue after receiving a transplant.
Supportive: ACEi/ARB for proteinuria and hypertension.
For ESRD, dialysis or kidney transplantation are options.
Anticonvulsants (gabapentin, carbamazepine) are used to treat pain.
Anticoagulation or antiplatelet medications if stroke risk.
Experimental: gene therapy (current studies) and chaperone treatment (migalastat).
Consultations
Neurologist: for CVA and stroke.
Cardiologist: LVH and arrhythmias.
Nephrologist: failing of the kidneys.
Geneticist: counselling, family screening.
Problems Faced in Fabry Disease
An X-linked lysosomal storage condition called Fabry disease causes lipid buildup in many organs, involving multiple systems. Renal failure, heart involvement, painful neuropathies, strokes, skin lesions (angiokeratomas), and gastrointestinal abnormalities are among the main problems that patients encounter. For positive results, a multidisciplinary approach and early diagnosis are essential.
Renal Dysfunction Issue: End-stage renal disease can result from progressive renal insufficiency.
Management: Serum creatinine, urea, uric acid, estimated GFR, cystatin C, and urinalysis for proteinuria and albuminuria are used to assess renal function annually. At baseline, a kidney ultrasound is conducted.
Nursing Interventions: Keep an eye on fluid balance and vital signs.
Teach patients to take their medications as prescribed, including antihypertensive drugs (ACE inhibitors and ARBs).
assistance with dialysis or post-transplant care, including nutritional guidance and emotional support.
Management: Annual and baseline cardiac evaluations using echocardiography and ECG.
Nursing Interventions: Keep an eye out for palpitations, shortness of breath, and chest discomfort.
Give distribute heart medicine and teach them how to recognise symptoms.
Encourage recommendations to follow up with specialists.
The issue with painful neuropathies is that they impair quality of life by burning sensations, acroparesthesias, and chronic pain.
Treatment options include enzyme replacement therapy (ERT), analgesics, and anticonvulsants.
Nursing Interventions: Use standardised measures to gauge pain.
Inform them about pain treatment techniques that don't include drugs, such physical therapy.
Encourage people to take their painkillers as directed.
Skin Lesions (Angiokeratomas) Issue: Possible infection and aesthetic issues.
Management: Standardised photography for monitoring; baseline and as-needed dermatology evaluation.
Nursing Interventions: Keep an eye out for developing or worsening skin lesions.
Teach them about skin care and cleanliness.
For psychological issues, offer emotional assistance.
Cerebrovascular Issues Problem: Increased risk of strokes, especially in young patients.
Management includes frequent INR monitoring for warfarin and the use of antiplatelet and anticoagulant medications if embolic stroke is present.
Nursing Interventions: Provide information on emergency response and stroke symptoms.
Keep an eye on your neurological condition.
Make sure that the medicine and lab follow-up are being followed.
Nutritional and Gastrointestinal Issues
Issue: gastrointestinal issues in youngsters, including discomfort, diarrhoea, and stunted development.
Management: creation of growth curves; GI evaluation at baseline and follow-up visits.
Nursing Interventions: Monitor nutritional status and weight.
Manage symptoms and provide education on dietary changes.
For customised plans, consult a dietician.
Cornea verticillata and other ocular anomalies are the issue of ophthalmological involvement.
Management: Initial ophthalmological evaluation and observation.
Nursing Interventions: Stress the value of routine eye checkups.
Keep an eye out for any fresh visual updates.
Enzyme Replacement Therapy (ERT) Issue: Multi-organ involvement and slow disease progression.
Management: In afflicted males and symptomatic females, ERT should be started as soon as possible. depending on body weight, infusions every two weeks.
Nurse interventions include giving ERT and keeping an eye out for infusion responses.
Inform patients and their families of the value of following instructions.
Keep track of and report any adverse effects.
Psychosocial and Quality of Life Problem: Chronic illness affects mental health and social functioning.
Management: counselling, support groups, and psychological testing.
Nursing Interventions: Offer referrals for counselling and emotional support.
Encourage dialogue with the medical staff.
Inform patients and their families on the course of the illness and coping mechanisms.
Needs for Rehabilitation
Issue: Difficulties in everyday living and loss of mobility.
Management: Physical and occupational therapy for walking and everyday life tasks.
Nursing Interventions: Help with at-home activities and treatment sessions.
Teach people how to use assistive technology.
Encourage self-reliance in self-care.
Notes
For more details visit https://www.ncbi.nlm.nih.gov/books/NBK435996/