Multidisciplinary care is essential in the management of Fabry disease

Pain is a hallmark of many cases of Fabry disease, and improvements in management could significantly improve the quality of life for patients.

A review published in the Journal of Clinical Medicine explored the mechanisms behind pain in Fabry disease and its pharmacological management, psychosocial implications and treatment. The article also highlighted the importance of interdisciplinary rehabilitation for pain reduction and a better quality of life for patients.

The most common manifestation of Fabry disease – an X-linked progressive lysosomal overload disease caused by a mutation in the GLA gene — is neuropathic pain that often develops in childhood and can be debilitating.

“Pain has a significant impact on male and female patients and results in a significant reduction in quality of life compared to the general population,” the authors wrote. “This appears to coincide with depression, anxiety and chronic fatigue in a significant percentage of people living with Fabry disease.”

Up to 62-80% of male patients and 30-65.3% of female Fabry patients experience neuropathic pain, with an average onset of 14.8 years and 19.8 years, respectively, based on long-term observational studies. This can include episodes of burning, sharp, stabbing, and stabbing pains in the limbs that worsen as patients exercise or experience changes in ambient temperature. Gastrointestinal pain is also common, both chronic and intermittent after eating.

The GLA The mutation causing Fabry codes for lysosomal hydrolase -galactosidase A (α-Gal A) and results in toxic accumulation of glycosphingolipids. These are in particular globortriaosylceramide (Gb3 or GL3) and lyso-Gb3, the deacylated form of Gb3.

The pain experienced by patients depends on the amount of residual enzyme activity. In the classic phenotype, which has no residual enzyme activity, pain is a hallmark of the disease.

Enzyme Replacement Therapy (ERT) is a recent development in Fabry treatment that has become the standard of care and changed the course of disease by preventing major organic complications and reducing pain. However, many patients do not see complete responses due to irreversible nerve damage.

Another treatment option, migalastat, is a daily oral pharmacological chaperone. Migalastat stabilizes mutant forms of α-Gal A in the endoplasmic reticulum to facilitate passage to lysosomes and enzymatic degradation of Gb-3.

An ongoing phase 3 study of iminosucre lucerastat has neuropathic pain as its primary endpoint. Other trials are looking at gene therapy as a potential treatment method. But there is a lack of therapies to effectively manage pain, while the authors noted that a holistic approach is key to managing pain.

“A multidisciplinary approach is important when forming an analgesic care plan involving not only metabolism and pain specialists, but also specialist pharmacists, pain psychologists and physiotherapists on the ward,” they said. writing.

Psychosocial support is another important aspect of managing Fabry as the most severe symptoms often appear in men in their youth, a crucial time for psychosocial development.

“A multimodal pharmacological approach using a combination of neuropathic agents such as gabapentinoids and duloxetine can facilitate reduction of neuropathic pain while achieving an opioid sparing effect. In turn, a reduction in neuropathic pain may also facilitate greater engagement in interdisciplinary rehabilitation to achieve a better quality of life, ”the researchers concluded.


Rajan JN, Ireland K, Johnson R, and Stepien K. Review of the mechanisms, pharmacological management, psychosocial implications and holistic treatment of pain in Fabry disease. J Clin Med. Published online September 15, 2021. doi: 10.3390 / jcm10184168

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