Contents
Definition
Fabry's disease is the most common among the hereditary lysosomal storage diseases and a so-called sphingolipidosis. Women are carriers of the hereditary system, while boys / men get the most symptoms of the disease (X-chromosomal recessive disease). The gene defect causes enzyme deficiency (alpha-galactosiderase (a-Gal A)). Thus, special fats (glycosphingolipids, globotriaosylceramide, Gb3) accumulate in the nerves, skin, kidneys, heart, brain, eyes and skeleton. The symptoms can be diffuse and Fabry's disease is often confused ("the great imitator") with rheumatic connective tissue disease and others.
Occurrence
The number of people with Fabry's disease is uncertain, but is estimated to be between one per 17.000 and one per 117.000 people. Thus, it is approx. 100 cases are known in Norway.
Symptoms of Fabry's disease
The symptoms that usually begin in children can be difficult to interpret. Boys with constant unclear pain in the arms, legs and in the stomach / intestine may give suspicion of Fabry's disease. Many organs can be affected.
The skeleton: Osteoporosis: Differential diagnosis: Other causes of osteoporosis in children. Bone necrosis that
begins on average at 10 years of age.
The nervous system: Burning pain, especially in hands and feet (Thin fiber neuropathy).
Welfare organ: Tinnitus (tinnitus). Reduced hearing. Dizziness.
Stroke at a relatively young age. Differential diagnosis: DaDA2, Sneddon's syndrome, antiphospholipid syndrome.
Kidneys; Protein in the urine (which may foam). Differential diagnosis: Autoimmune kidney inflammation by, among other things SLE. Kidney cysts. Reduced kidney function
Heart: Arrhythmias. Heart valve injuries (aortic and mitral valves)
Skin: Angiokerathoma are small, not painful bullets (papules / nodules), most often on the thighs, abdomen and over the pelvic area or on the hands (see photo above). Telangiectasia. anhidrosis (lack of sweat). Raynaud's -like white and cold hands or burning pain (which is unusual for Raynaud's phenomenon)
Dry mouth and dry eyes: Reduced saliva and tear production. Differential diagnosis Sjögren's syndrome, Sarcoidosis.
Eyes: Cornea verticillata (The corneas become blurred), May be a onset symptom
Other: Fatigue. Abdominal pain. Weight loss
Examinations for Fabry's disease
Medical history includes whether boys / men in close relatives have current symptoms (X-chromosomal hereditary). Typical symptoms (see above) are requested.
Clinical examination can reveal high blood pressure, impaired kidney function, decreased tear production (Schirmer's test), enlarged heart with arrhythmias, painful nerve symptoms in the hands and feet, bleeding in the skin, blurred lens and corneal changes in the eyes. Skin changes with angiokeratoms, Raynaud's phenomenon.
Laboratory tests may include electrolytes and kidney function tests. Urine can show proteins and fat bodies. Specific diagnosis can be made if enzyme analysis shows too low alpha-Gal A activity in lymphocytes or plasma.
Imaging consists of chest X-ray, possible CT of the skeleton (osteonecrosis), CT, CT angiography, MRI, MR angiography and M-spectroscopy, as well as DEXA scanning for osteoporosis.
Other. ECG and ultrasound examination of the heart (echocardiography) for mapping of cardiac manifestations such as arrhythmia and structural changes.
Tissue sample (biopsy) from skin or kidneys may contribute to the diagnosis. Deposits of fats in the form of glycolipids are typical. Electron microscopy of kidney tissue shows concentric layers with inclusions in the form of "zebra bodies".
Diagnosis
Thorough medical history (family / inheritance, symptoms), clinical examination + measure level of alpha-galactosiderase activity.
Similar diseases / differential diagnoses in Fabry's disease
- DADA2 (children / young people with strokes)
- Dermatomyositis in Children (JDM)
- Erytromelalgia
- Fibromyalgia
- Hypertrophic cardiopathy of other reasons
- Irritable bowel syndrome
- Juvenil artritt (JIA)
- Menier's disease
- Multiple sclerosis
- Kidney disease of other reasons
- Rheumatic fever
- Telangiectasia of other reasons
Treatment of Fabry's disease
Enzyme therapy (alpha-galactosidase A) may stop the development of the disease and partially reverse the symptoms. Gene therapy is being tested. Symptom treatment: Medications for pain or cramps, treat kidney failure. Pacemaker or ICD (defibrillator) in some cardiac arrhythmias
Specialists: Pediatrician, endocrinologist, cardio-renal-dermatologist.
Prognosis
After one stroke, there is a risk of several strokes in the course. Kidney failure with transplantation may be necessary. Women who are genetically heterozygous have a much milder disease compared to men.
