Possible symptoms of Fabry disease

As many symptoms are unspecific, it is difficult to recognize Morbus Farby from them. So existenz of several symptoms are only an indication and must be proofed by genetic testing!

Neurological symptoms (PNS=periphereral nervous system)

With the separation into neurological and other symptoms, we want to show, how damage to the nerves can affect the body or organs in many ways.

Small-Fiber-Neuropathie / Polyneuropathie

Polyneuropathies are generalized diseases of the peripheral nervous system, which lead to damage and functional disorders of sensory, motor and/or vegetative nerve fibers.

The peripheral nervous system (PNS) consists of the nerves and ganglia outside the brain and spinal cord, the central nervous system (CNS). The peripheral nervous system is divided into the somatic nervous system, and the autonomic nervous system. The somatic nervous system is under voluntary control, and transmits signals from the brain to end organs such as muscles. The sensory nervous system is part of the somatic nervous system and transmits signals from senses such as taste and touch (including fine touch and gross touch) to the spinal cord and brain. The autonomic nervous system is a ’self-regulating‘ system which influences the function of organs outside voluntary control, such as the heart rate, or breathing, circulation, digestion, bladder and sexual function. Other bodily processes are also regulated via the autonomic nerves, such as sweating, temperature and pupillary reactions.

In most cases, healing is not possible. As the disease progresses, nerve cells can die so that their function get completely lost.

Sensory symptoms

  • Burning pain in hands and feet
  • Stabbing or stinging pain
  • Pain that increases at rest or at night
  • Chronic jaw and facial pain
  • Burning of the oral mucosa
  • Severe hypersensitivity to touch, even when lightly touched (blanket, clothing)
  • Sensory disturbances, feeling of fur and numbness, „tingling“ or „pins and needles“ on the skin
  • The temperature sensation in the area of the damaged nerves may be disturbed or no longer present at all
  • Itching
  • Painless wounds
  • Wound healing disorders
  • Uncertainty grasping something
  • Coordination disorders
  • Disturbance of depth sensitivity
  • Disorder of deep sensibility / proprioceptive perception
  • Insecure gait, especially in the dark
  • Falls on uneven ground
  • Frequent bumping into doors, edges of tables, objects
  • Biting your tongue while eating
  • Balance disorders, unsteady gait
  • The eyes are needed for orientation (position of the feet)

Proprioception refers to the perception of one’s own body according to its position in space, the positions of the head, torso and limbs in relation to one another and their changes as movements together with the perception of heaviness, tension, strength and speed. This is a personal feeling. Various senses are related to one another to perceive one’s own body in terms of position, posture, position, tension and movement. In addition to signals from sensory cells in the skin (sense of touch) and the vestibular organs (sense of balance), these are mainly those from receptor cells of deep sensitivity, which are therefore also called proprioceptors. These are mechanoreceptors that respond as sensitive end organs in muscles, tendons and joints to the condition and changes in condition of the musculoskeletal system (e.g. muscle spindles, Golgi tendon organs, joint sensors).

Motor symptoms

  • Muscle weakness in feet, lower legs and hands
  • Muscle wasting, decreasing endurance
  • Muscle twitching (fasciculations)
  • Restlessness in the legs
  • Muscle cramps (especially calf cramps)
  • Muscle atrophy (decrease in muscle mass), atrophy of the small muscles of the foot leading to stressing of the arch of the foot (concave foot) and atrophy of the short toe extensors (hammer toe)
  • Muscle pain (myalgia)
  • Involuntary spontaneous movements

Autonomic neuropathy


Gastrointestinal system / gastroparesis

  • Difficulties swallowing /disorder of esophageal motility, reflux
  • Stomach pain, indigestion, nausea, vomiting, flatulence
  • Delayed gastric emptying, premature feeling of satiety
  • Dyspepsia
  • Gastric paralysis
  • Diarrhea/constipation
  • Constipation/ obstipation
  • Nocturnal diarrhea
  • Anal incontinence
  • Increased risk of gallstones
  • Disturbed function of the pancreas, loss of reflex secretion
  • Diverticulosis

Urogenital System

  • Bladder incontinence – unable to control bladder, leaks, constant urge to urinate
  • Urinary retention
  • Loss of bladder sensation with late onset of urge to urinate; this can lead to bladder overfilling and overflow incontinence, decrease in urinary frequency and dribbling, and involuntary urine leakage
  • Male: erectile dysfunction, retrograde ejaculation
  • Female: Loss of sexual desire (libido), lack of lubrication, ie dry mucous membranes, and painful inflammation such as vaginitis

Skin/mucous membranes

  • Dry skin, mucous membranes
  • Poor wound healing
  • Loss of body hair

Eyes

  • Dry eyes (sicca syndrome)
  • Increased glare sensitivity
  • Disorder of pupillary reflex
  • Optic neuropathy
  • Visual field defects

Ear

  • Hearing loss
  • Ear noise

Cardiovascular system

  • Heart palpitations
  • Resting tachycardia
  • Decrease in heart rate variability
  • Decrease or absence of circadian rate and blood pressure rhythms
  • Painless myocardial ischemia or infarction
  • Exercise intolerance
  • Perioperative cardiovascular instability
  • Sudden cardiac death
  • Malignant arrhythmia
  • Orthostatic hypotension (OH) Complaints include dizziness, blurred vision, neck pain radiating to shoulders (coat hanger pain)
  • POTS (Postural orthostatic tachycardia syndrome) is a condition in which a change from lying to standing causes an abnormally large (or higher than normal) increase in heart beat rate. This occurs with symptoms that may include lightheadedness, trouble thinking, blurred vision, or weakness.

Vasomotor disorders

Vasomotor: Adjusting the diameter of blood vessels by constricting or expanding the smooth muscle cells in the blood vessel walls. The vasomotor system is mainly controlled by nerves (mainly by the sympathetic nervous system), but is also influenced by vasoactive substances such as histamine, prostaglandins and hormones.

  • Sensation of heat and cold (e.g. cold hands and feet)
  • circulatory problems
  • Headache
  • Sweating
  • Edema (vasodilatation, arteriovenous shunts)
  • Hypertension
  • Vasovagal syncope (fainting)

Respiratory System

  • Sleep apnoea
  • Respiratory depression
  • Breathing arrest

Impaired sweat gland function / Sudomotor dysfunction

  • An-/ hypohidrosis reduced sweating leading to overheating, with skin flushing
  • Heat intolerance/avoidance of sunlight
  • Hyperhidrosis excessive sweating
  • Heavy sweating, especially at night

Further Symptoms

Since the symptoms can sometimes not be clearly assigned, please also note the neurological symptoms.

Due to the lack or absence of alpha-galactosidase, glycosphingolipids – especially globotriaosylceramide (Gb3) – are insufficiently degraded and accumulate within the lysosomes. The cells damaged by glycosphingolipid deposits can be found in:

  • Kidneys (mesangial, endothelial and tubular epithelial cells, podocytes),
  • Heart (myocardial cells, endothelial cells and fibrocytes)
  • peripheral nervous system (neurons of the dorsal root ganglia and the autonomic nervous system) and
  • Blood vessels (endothelial, perithelial and smooth muscle cells)


Because the progressive accumulation of glycosphingolipids affects numerous organs and tissues, patients often present with a variety of features and symptoms, which may vary in severity.

Further mechanisms are currently being researched; according to the current state of research, damage does not only occur due to the deposit of Gb3!

Pain (see also symptoms of polyneuropathy)

  • Neuropathic pain/Small fiber neuropathy
  • Chronic pain in the joints
  • Episodic painful crises (Fabry crises) Fever, exercise, fatigue, stress or rapid temperature changes can trigger the pain crises
  • Persistent pain in the mouth, jaw and face

Kidney

  • Microalbuminuria
  • Proteinuria
  • Nephropathy
  • Glomerulosclerosis, renal atrophy
  • Reduced Glomerular Filtration Rate
  • Progressive renal insufficiency up to the need for dialysis
  • Parapelvic renal cysts

CNS (central nervous system=brain)

  • Headache, migraine
  • TIA (transient ischemic attack)
  • Stroke
  • Dolichoectasia of the basilar artery
  • White Matter Lesions
  • Decreased cognitive performance such as memory disorders or a reduced ability to concentrate
  • Vascular dementia

Heart and vascular system diseases (see also symptoms of polyneuropathy)

  • Palpitations
  • Cardiac arrhythmia
  • Atrial and ventricular tachyarrhythmias
  • Symptomatic bradycardia
  • Atrial fibrillation
  • Heart valve diseases (valve dysfunction, mitral valve, aortic valve)
  • Heart failure
  • Left ventricular hypertrophy (heart wall thickening)
  • Intramyocardial fibrosis
  • Cardiomyopathy (heart muscle disease)
  • Reduced heart rate variability
  • Angina pectoris
  • Prominent papillary muscle
  • ECG changes with short P wave and PR interval, increase in QRS width and repolarization disorders
  • Myocardial infarction
  • Hypertension
  • Abnormal heart rate variability
  • Vasculopathy, vascular abnormalities
  • Intimal fibrosis, vessel wall thickening
  • Vascular ectasia (bulging (ectasia) of a blood vessel)
  • Lymphedema

Blood changes

  • Anemia

Metabolism

  • Dyslipidemia

Eye (see also symptoms of polyneuropathy)

  • Corneaverticillata (corneal opacities)
  • Lens opacities (so-called Fabry cataracts)
  • Tortuositas vasorum (tortuosity of the retina and conjunctiva)
  • Optic neuropathy, optic atrophy, damage to the optic nerve
  • Visual field defects
  • Dry eyes (sicca syndrome)

Ear (see also symptoms of polyneuropathy)

  • Hearing loss affects both ears and affects all frequencies, but particularly high frequencies
  • Tinnitus
  • Dizziness
  • Disorders of the vestibular system

Skin / mucous membrane (see also symptoms of polyneuropathy)

  • Angiokeratomas of the skin, lips or oral mucosa
  • Telangiectasias
  • Disorders of sweat secretion
  • Dry skin / mucous membranes

Lung

  • Dry cough
  • Obstructive airway disorder
  • Dyspnea

Bones

  • Ossifications
  • Osteopenia
  • Osteoporosis

Gastrointestinal system (see also symptoms of polyneuropathy)

  • Food intolerance

Thyroid

  • Hypothyroidism (underactive thyroid)

Sleep disorders / exhaustion

  • Fatigue
  • EDS/ETS Excessive daytime sleepiness
  • Inability or difficulty to fall asleep, awaken during the night and cannot fall back asleep and waking up too early
  • Lethargy and tiredness
  • Reduced resilience
  • Sleep apnea

General Symptoms

  • Unexplained fever
  • Depressions
  • Decreased quality of life
  • Reduced life expectancy

Other commonly reported symptoms:

  • Osteoarthrosis
  • Lipoma formation
  • Fibromatoses
  • Hashimoto
  • Ganglion
  • Multiple cyst formation
  • Swollen lymph nodes
  • Nosebleeds
  • Frequent inflammation of the oral mucosa, aphthae
  • Increased salivation, strong flow of secretions in the nasopharyngeal zone
  • Psoriasis (scalp)
  • Abscesses
  • Enthesitis frequent inflammation of the tendon attachments (e.g. trochanter tendinosis)
  • Asthma
  • Diabetes
  • Obesity