Paula and Bobby
Parents of Lillie
What is Fabry Disease?
Fabry syndrome occurs mainly in males, and is the result of mutations in the genes that produce the enzyme alpha-galactosidase A.
The disease is considered a multi-system, progressive disorder and a lysosomal storage disease.
What gene changes cause Fabry Disease?
The syndrome is the result of a defective GLA gene, responsible for producing the enzyme alpha-galactosidase A.
This enzyme is responsible for breaking down the fat GB3/GL-3. Without this enzyme the fat builds up in the body and triggers Fabry syndrome and its symptoms.
As an X-linked genetic disorder the syndrome is more common in males than females.
What are the main symptoms of Fabry Disease?
The main symptoms of the syndrome include episodic pain, dark red spots on the skin and an inability to sweat effectively.
Individuals with the syndrome experience kidney and heart issues also. Clouding of the corneas is also not uncommon.
Other health conditions associated with the syndrome include gastrointestinal issues and joint pain, as well as an inability to gain weight and higher risk for stroke.
Possible clinical traits/features:
Vertigo, Transient ischemic attack, X-linked recessive inheritance, Reduced bone mineral density, Thick lower lip vermilion, Telangiectasia of the skin, Tenesmus, Juvenile onset, Vomiting, Respiratory failure, Sensorineural hearing impairment, Optic atrophy, Seizure, Renal insufficiency, Proteinuria, Paresthesia, Dysautonomia, Fasciculations, Delayed puberty, Coronary artery atherosclerosis, Corneal dystrophy, Anemia, Coarse facial features, Conjunctival telangiectasia, Congestive heart failure, Emphysema, Diarrhea, Diabetes insipidus, Developmental regression, Nephrotic syndrome, Malabsorption, Opacification of the corneal stroma, Short stature, Hematuria, Muscle spasm, Hypohidrosis, Cognitive impairment, Glomerulopathy, Hypertension, Hyperkeratosis, Hypertrophic cardiomyopathy, Angiokeratoma, Angina pectoris, Anorexia, Chronic pulmonary obstruction, Cerebral ischemia, Arthritis, Arthralgia, Abnormality of femur morphology, Abnormal renal tubule morphology, Abnormal mitral valve morphology, Behavioral abnormarlities
How does someone get tested for Fabry Disease?
The initial testing for Fabry syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Fabry Disease
Fabry Disease is an x-linked recessive metabolic condition characterized by dark red skin lesions as well as pain in the extremities and genitals. Corneal opacity, cardiac defects and renal failure are also commonly seen. Initial symptoms are usually episodes of burning, intense pain felt deep in the skin, which may last for minutes or persist for weeks. (Ries et al., (2003). This often occurs in the fingers and toes, but may also present in the abdomen and genitalia, and is influenced by temperature. Thus patients often seek cool environments. At the same time, skin lesions appear as clusters of dark red papules at about 1mm in diameter. These often develop on the lower trunk and first appear in late childhood, but become more profuse during the third and fourth decades. Renal failure and cerebrovascular accidents are relatively common. The ocular signs include opacification of the cornea, said to be whirl-like in configuration. Edema of the eyelids and retinal vessel thrombosis have also been described. Death usually occurs as a result of renal failure in middle life, but even within families there is great variability, as reported by Verovnik et al., (2004). Cardiac defects occur in 30% of patients and include mitral valve prolapse and cardiomyopathy. Redonnet-Vernhet et al., (1996) described monozygotic female twins where one was affected due to uneven X inactivation. MacDermot et al., (2001) reviewed 98 cases. Mean survival was 50 years. Neuropathic pain was present in 77%. Cerebrovascular complications occurred in 24% and renal failure in 30%. MacDermot et al., (2001) also studied a cohort of 60 obligate carrier females. Median survival was 70 years. 30% of carrier females were deemed to have multiple and serious manifestations. 30% had transient ischaemic attacks or cerebrovascular accidents and 3% had renal failure. 3% had disabling neuropathic pain. About 10% had a personality disorder or suicidal thoughts. Further female cases were reported by Guffon (2003). MacDermot et al., (2001) reviewed 98 cases. Mean survival was 50 years. Neuropathic pain was present in 77%. Cerebrovascular complications occurred in 24% and renal failure in 30%. Germain et al., (2005) reported that of 23 patients, 87% had a significantly decreased bone density, either representing as osteopenia or osteoporosis. Germain et al., (2006) reported four patients with the Chiari I malformation. MacDermot et al., (2001) also studied a cohort of 60 obligate carrier females. Median survival was 70 years. 30% of carrier females were deemed to have multiple and serious manifestations. 30% had transient ischaemic attacks or cerebrovascular accidents and 3% had renal failure. 3% had disabling neuropathic pain. About 10% had a personality disorder or suicidal thoughts. Note the two sisters reported by Lipsker et al., (2006), with angiokeratoderma corporis diffusum, without any enzymatic or molecular evidence of Fabry Disease. The same situation was reported by Lu et al., (2015). Rolfs et al., (2005) looked for mutations in 721 German adults aged between 18-55 years that, who had, had an unexplained stroke. Nearly 5% of males and 2.4% of females were found to carry mutations. Accordingly, Germain et al., (2005) reported that 87% of 23 patients had a significantly decreased bone density, either representing as osteopenia or osteoporosis. Juchniewicz et al. (2017) described 12 carrier females from families with Fabry Disease. Age of onset was between five and 35 years. Initial symptoms included pain (extremities, hands and feet, abdominal, head, burning sensation), increased body temperature, hypohidrosis, fatigue, fainting, arrhythmia, and chronic proteinuria. Evaluation of X chromosome inactivation did not show correlation with severity of manifestations.
* This information is courtesy of the L M D.
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