Nervous system and Fabry disease, from symptoms to diagnosis: damage evaluation and follow-up in adult patients, enzyme replacement, and support therapy

Abstract

The X-linked genetic Fabry disease causes multiorgan lesions due to intracellular storage of the substrate globotriaosylceramide. Neurological involvement ranges from painful, small fiber neuropathy to cerebrovascular disorders to multifocal aggressive forms. Disease identification through proper differential diagnosis and timely assessment of organ damage should guide a careful treatment planning. Mainstay treatment, include enzyme replacement and support therapy. Neurologists have a pivotal role in early instrumental and clinical detection of organ damage. A panel of experts has developed a set of consensus recommendations to guide the approach of neurologists to Fabry disease.

Efficient Uptake of Recombinant α-Galactosidase A Produced with a Gene-Manipulated Yeast by Fabry Mice Kidneys

“…ERT with recombinant human GLAs produced by mammalian cells has been reported to have beneficial effects in Fabry patients (alleviation of neuropathic pain, improvement of sweat function, regression of hypertrophic cardiomyopathy and also stabilization of kidney function), although it is not effective in the advanced stages of the disease (8)(9)(10)(13)(14)(15)(16). However, there are various disadvantages of the production of enzymes using mammalian cells (that is, the high cost, the complicated procedure and difficulty in performing a large scale-up and the risk of infections through cultivation in the presence of bovine serum).…”

“…These recombinant GLAs are glycoproteins having both complex type and highmannose type sugar chains produced by cultured mammalian cells, and it is thought that they are incorporated into cells mainly via mannose 6-phosphate (M6P) receptors in many organs (11) except for the liver, in which uptake by hepatocytes and Kupffer cells occurs mainly through asialoglycoprotein receptors and mannose ones, respectively (12). The incorporated GLAs cleave the glycosphingolipids deposited in Fabry organs, and there have been many clinical reports describing the efficacy of these recombinant enzymes (13)(14)(15)(16). However, there are some disadvantages of producing recombinant enzymes using mammalian cells.…”

Guía clínica: consenso para Chile en enfermedad de Fabry

“…La neuropatía dolorosa (sensitiva) es una manifestación temprana de la enfermedad, ya que suele aparecer alrededor de los 11 años de edad, en promedio, e incluso antes, mientras que los trastornos cerebrovasculares ocurren, de manera típica, a partir de la tercera o cuarta décadas de la vida y la edad promedio de aparición de los primeros síntomas de este tipo es de 34 años en los hombres y de 40 años, entre las mujeres 2,5,6,[9][10][11] .…”

“…El estudio histológico de las lesiones cutáneas y renales, muchas veces es el primer paso en la sospecha diagnóstica de la EF 2,6,7,9,22 : 3. Diagnóstico bioquímico.…”

The neurological manifestations of Fabry disease. A review

“…Болезнь может мими-крировать под другую патологию, например, рассеянный склероз [61]. При наличии полиорганной патологии, не-обходимо шире подходить к проблеме и лечить не десяток одновременно протекающих болезней, а сосредоточиться на наследственном заболевании [62][63][64][65].…”