Fabry disease is caused by the lack of an enzyme needed to metabolize lipids, which are fat-like substances that include oils, waxes, and fatty acids. The enzyme is known as ceramide trihexosidase, also called alpha-galactosidase-A. The deficiency of this enzyme causes insufficient breakdown of lipids, which build up to harmful levels in the eyes, kidneys, autonomic nervous system, and cardiovascular system. As the gene that is altered is carried on a mother’s X chromosome, her sons have a 50 percent chance of Fabry disease inheritance, and her daughters have a 50 percent chance of being a carrier. Fabry disease is classified into two types: Classic and Late-onset.
Classic Fabry disease, which is the less common form, typically manifests in childhood, while late onset Fabry disease, as its name suggests, usually begins with symptoms in the 30s or 40s.
The estimated prevalence of FD is 1/40 000 to 1/117 000 live births globally. The incidence of Fabry disease in India is likely to be higher because of the tradition of consanguineous marriage in some parts of the country.
Fabry disease is caused by mutations in the GLA gene, which is located in the X chromosome (one of the two sex chromosomes, the other being the Y chromosome).
Fabry disease symptoms usually begin during childhood or adolescence and include:
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The heart may also become enlarged and the kidneys may become progressively involved.
Some other symptoms include:
In male patients, the diagnosis of Fabry disease can be done through enzyme tests, which measure the activity of the alpha-galactosidase A (Gal A) enzyme in the blood. These tests use blood drawn from the arm and can be done at a doctor’s office or in a lab setting. In the case of Fabry disease in females, Gal A’s activity is often within the normal range, limiting its usefulness to these individuals. Therefore, a genetic test is required for females, and is also recommended to confirm the diagnosis in male Fabry patients.
The most definitive assessment, a genetic test, looks for disease-causing mutations in the GLA gene. Both males and females only have to inherit one mutated GLA gene copy to develop the disease. Cells from a sample of blood or saliva are usually used in such testing. This type of test should be considered for any individual with a confirmed or suspected clinical diagnosis of Fabry, or a family history of the disease.
Prenatal testing and newborn screening
Enzyme and genetic testing also can be done before birth to see if an unborn baby has a disease-causing GLA mutation.
Newborn screening for Fabry typically involves collecting a blood spot from a heel prick and analyzing the levels of Gal A activity.
A test for lyso-Gb3, another fatty substance that accumulates in the blood or in the urine as a result of Gal A deficiency, also can help to achieve a Fabry diagnosis, particularly in female patients, and indicate the severity of the disease.
Fabrazyme®, developed by Sanofi Genzyme, is the first enzyme replacement therapy (ERT) for Fabry disease. Another ERT, Replagal®, developed by Takeda, is in use in many countries, including Canada, Russia, the United Kingdom, Mexico, Israel, and many members of the European Union. However, it has not been approved by the U.S. Food and Drug Administration (FDA).
Galafold® (migalastat) is an oral medication developed by Amicus Therapeutics as a treatment for Fabry, which has been approved in some countries such as the US, EU, Japan, Switzerland, Israel, Australia, South Korea, Canada, and Argentina.
Treatment for Fabry is extremely expensive and life-long, but is available to some patients in India through humanitarian aid.
To get information about ongoing/future clinical trials in India for Fabry, please visit here.
If you or someone you know from India has been diagnosed with Fabry, please register with us by filling out this form to get further information and support.
People who have Fabry don’t have or lack the enzyme alpha-galactosidase A that breaks down certain lipids or fats. These fats get collected in blood vessels and tissues, raising the risk of heart attack, stroke and kidney failure. This genetic condition is passed from parents to the child.
Fabry disease symptoms include:
Published data from the Fabry registry indicates that male Fabry patients live an average of about 58 years, compared to about 75 years for men in the general population in the U.S. For women with Fabry disease, the average life expectancy is around 75 years compared to 80 years for women in the U.S. general population.
Symptoms of classic Fabry disease appear during childhood or the teenage years. One of the main symptoms—a painful burning sensation in the hands and feet—may be noticeable as early as age two. Symptoms get progressively worse over time.
People with late-onset Fabry disease don’t have symptoms until they’re in their 30s or older. The first indication of a problem may be kidney failure or heart disease.
Fabry disease treatment in India is extremely expensive, costing anywhere from several lakhs to a few crore rupees per year. A few companies have been providing free treatment for Fabry disease in India under their charitable access programmes. However, at present, getting treatment under charitable access is very difficult as the companies are not accepting any more patients. We advise you to get yourself/the patient enrolled on Government of India’s portal for crowdfunding and CSR donations for rare diseases by meeting the doctor at your nearest COE with all medical reports for medical evaluation. You can find the details of your nearest COE here.
In addition, you may request the doctor to explore the possibility of getting charitable access to treatment by asking the doctor to contact these companies.
Also, please register yourself with the LSDSS by completing this form to get support and know the latest developments about the disease.
Ugonjwa wa Fabry unatokana na ukosefu wa enzyme inayohitajika kuharibu lipids, ambayo ni vitu vinavyofanana na mafuta ambavyo ni pamoja na mafuta, waxes, na asidi za mafuta. Enzyme hiyo inajulikana kama ceramide trihexosidase, ambayo pia huitwa alpha-galactosidase-A. Ukosefu wa enzyme hii husababisha uharibifu wa lipids, ambayo hujenga hadi viwango vyenye madhara katika macho, figo, mfumo wa neva wa kujitegemea, na mfumo wa moyo na mishipa. Kwa kuwa chembe ya urithi iliyobadilishwa ni ya mama, wanawe wana uwezekano wa asilimia 50 wa kuambukizwa ugonjwa wa Fabry, na binti zake wana uwezekano wa asilimia 50 wa kuwa wabebaji. Ugonjwa wa Fabry umegawanywa katika aina mbili: Ugonjwa wa kawaida na ugonjwa wa kuchelewa. Ugonjwa wa Fabry wa kawaida huanza katika miaka ya 30 au 40. Ugonjwa huu unakadiriwa kuwa unaenea kwa asilimia 1 kati ya 40,000 na 117, 000 ya watoto wanaozaliwa wakiwa hai duniani kote. Ugonjwa wa Fabry unaonekana kuwa wa kawaida zaidi nchini India, kwa sababu ya utamaduni wa ndoa za jamaa katika sehemu fulani za nchi. Ugonjwa wa Fabry unatokana na mabadiliko katika jeni la GLA, ambalo liko katika kromosomu ya X (moja ya kromosomu mbili za ngono, nyingine ni kromosomu ya Y). Dalili za ugonjwa wa Fabry huanza wakati wa utoto au ujana na ni pamoja na: Moyo unaweza pia kuongezeka na figo zinaweza kuhusika hatua kwa hatua. Katika wagonjwa wa kiume, ugonjwa wa Fabry unaweza kugunduliwa kupitia vipimo vya enzyme, ambavyo hupima shughuli ya alpha-galactosidase A (GalA) enzyme katika damu. Uchunguzi huo hutumia damu inayotokana na mkono na inaweza kufanywa katika ofisi ya daktari au katika maabara. Katika kesi ya ugonjwa wa Fabry katika wanawake, shughuli ya Gal A<unk>s mara nyingi iko ndani ya safu ya kawaida, ikipunguza manufaa yake kwa watu hawa. Kwa hiyo, mtihani wa maumbile unahitajika kwa wanawake, na pia unapendekezwa kuthibitisha utambuzi katika wagonjwa wa Fabry wa kiume. Uchunguzi wa chembe za urithi unachukuliwa kwa mara ya kwanza ni uchunguzi wa chembe za urithi zinazohusika na ugonjwa wa GLA. Wanaume na wanawake wanahitaji tu kurithi nakala moja ya jeni ya GLA iliyobadilika ili kuendeleza ugonjwa huo. Kwa kawaida chembe kutoka kwa sampuli ya damu au mate hutumiwa katika majaribio hayo. Utafiti huu unapaswa kuchukuliwa kwa mtu yeyote aliye na uthibitisho wa kliniki wa Fabry, au historia ya familia ya ugonjwa huo. Uchunguzi wa kabla ya kuzaliwa na uchunguzi wa watoto wachanga: Uchunguzi wa kijiografia na wa kijiografia unaweza kufanywa kabla ya kuzaliwa ili kuona kama mtoto ambaye hajazaliwa ana mabadiliko ya GLA yanayosababisha ugonjwa. Uchunguzi wa Fabry kwa watoto wachanga kwa kawaida unahusisha kukusanya doa la damu kutoka kwa kidonda cha kisigino na kuchambua viwango vya shughuli za Gal A. Liso-Gb3 - kipimo cha mafuta ambayo hujipanda katika damu au mkojo kutokana na upungufu wa Gal A - pia inaweza kusaidia kufikia utambuzi wa Fabry, haswa kwa wagonjwa wa kike, na kuonyesha uzito wa ugonjwa. Fabrazine, ambayo imetengenezwa na Sanofi Genzyme, ni tiba ya kwanza ya kubadilisha enzyme (ERT) kwa ugonjwa wa Fabry. Replagal, ambayo ni dawa ya ERT, imetengenezwa na Takeda na inatumika katika nchi nyingi, ikiwa ni pamoja na Canada, Urusi, Uingereza, Mexico, Israel, na wanachama wengi wa Umoja wa Ulaya. Hata hivyo, haijaidhinishwa na Shirika la Chakula na Dawa la Marekani (FDA). Galafold (migalastat) ni dawa ya mdomo iliyotengenezwa na Amicus Therapeutics kama matibabu ya Fabry, ambayo imeidhinishwa katika nchi zingine kama vile Marekani, EU, Japan, Uswisi, Israel, Australia, Korea Kusini, Canada na Argentina. Matibabu ya Fabry ni ghali sana na ya muda mrefu, lakini inapatikana kwa baadhi ya wagonjwa nchini India kupitia misaada ya kibinadamu. Kwa habari zaidi kuhusu majaribio ya kliniki ya sasa na ya baadaye ya Fabry, tafadhali tembelea hapa. Ikiwa wewe au mtu unayemjua kutoka India amepatikana na Fabry, tafadhali jiandikishe nasi kwa kujaza fomu hii ili kupata habari zaidi na msaada. Watu walio na Fabry hawana au hawana enzyme ya alpha-galactosidase A ambayo huvunja lipidi au mafuta fulani. Mafuta hayo hukusanyika katika mishipa ya damu na tishu, na hivyo kuongeza hatari ya kupatwa na mshtuko wa moyo, kiharusi, na kushindwa kwa figo. Hali hii ya urithi hupitishwa kutoka kwa wazazi hadi kwa mtoto. Kwa mujibu wa utafiti uliofanywa na utafiti wa utafiti wa Fabry, wanaume wanaishi kwa wastani miaka 58 ikilinganishwa na wanaume wanaishi kwa miaka 75 ikilinganishwa na wanawake wanaishi kwa wastani miaka 80. Dalili za ugonjwa wa Fabry wa kawaida huonekana wakati wa utoto au miaka ya ujana. Mojawapo ya dalili kuu - hisia yenye uchungu ya kuchoma mikononi na miguu - yaweza kuonekana mapema kama umri wa miaka miwili. Dalili hizo huzidi kuwa mbaya kadiri wakati unavyopita. Watu wenye ugonjwa wa Fabry wenye mwanzo wa marehemu hawana dalili mpaka wawe na umri wa miaka 30 au zaidi. Dalili ya kwanza ya tatizo hilo huenda ikawa kushindwa kwa figo au ugonjwa wa moyo. Matibabu ya ugonjwa wa Fabry nchini India ni ghali sana, yakigharimu mahali popote kutoka lakhs kadhaa hadi crore chache za rupies kwa mwaka. Kampuni chache zimekuwa zikitoa matibabu ya bure ya ugonjwa wa Fabry nchini India chini ya programu zao za upatikanaji wa misaada. Hata hivyo, kwa sasa, kupata matibabu chini ya upatikanaji wa misaada ni vigumu sana kama makampuni si kukubali wagonjwa zaidi. Tunapendekeza kujiandikisha kwenye tovuti ya Serikali ya India kwa ajili ya misaada ya umma na CSR kwa ajili ya magonjwa ya nadra kwa kukutana na daktari katika COE yako ya karibu na ripoti zote za matibabu kwa tathmini ya matibabu. Unaweza kupata maelezo ya COE yako ya karibu hapa. Kwa kuongezea, unaweza kumwuliza daktari kuchunguza uwezekano wa kupata upatikanaji wa matibabu ya hisani kwa kumwomba daktari kuwasiliana na kampuni hizi. Pia, tafadhali kujiandikisha na LSS kwa kujaza fomu hii ili kupata msaada na kujua maendeleo ya hivi karibuni kuhusu ugonjwa.