2026-04-14 | An Essential Parameters of Fucosidosis Include History of the Disease, Other Lysosomal Storage Disease, Symptoms as well as Clinical Features, Treatment as well as Therapeutic Options

Fucosidosis is a rare lysosomal storage disease occurred by α-L-fucosidase deficiency because of mutation especially in the FUCA1 gene. This enzyme plays an important role regarding catabolism of fucose-containing glycoproteins, glycolipids, and oligosaccharides within the lysosome. Fucose-rich substrates are deposited in lysosomes as a result of mutations in FUCA1, which cause either reduced enzyme activity or complete loss of function. Undigested substrates cause lysosomes to swell, leading to secondary storage problems that affect other metabolic pathways. The central nervous system is especially vulnerable,along with lysosomal dysfunction creating microglial activation, inflammation, and neuronal loss, resulting in the neurodegenerative symptoms of fucosidosis. Neuroinflammation contributes to secondary damage, along with neuronal apoptosis, axonal degeneration, and synaptic dysfunction, enhancing the disease process. Chronic neuroinflammation disrupts synaptic plasticity as well as neuronal survival, resulting in progressive intellectual disability, learning difficulties, and loss of previously acquired skills. Inflammatory cytokines and lysosomal burden in motor neurons and associated pathways contribute to ataxia, spasticity, and hypotonia, which are common motor symptoms in fucosidosis. Raised neuroinflammatory markers can enhance neuronal excitability, resulting in the frequent occurrence of epilepsy in affected individuals. So, fucosidosis is manifested by rapid mental and motor loss, along with growth retardation, coarse facial features, hepatosplenomegaly, telangiectasis or angiokeratomas, epilepsy, inguinal hernia, and dysostosis multiplex. Patients generally die at an early age. Treatment of fucosidosis is a great challenge, and there is currently no definitive effective treatment. Hematopoietic cell transplantation studies are ongoing regarding the treatment of fucosidosis. Whatever it may be, early diagnosis of this disease and treatment shows an effectiveness. In addition, the body’s immune system reduces because of chemotherapy applied after transplantation, leaving the body vulnerable to microbes and infections, and the risk of death is more along with this treatment. In another treatment method, gene therapy, the use of retroviral vectors, is enhancing because of their easy integration, high cell efficiency, and safety. Preclinical research is being conducted for fucosidosis using an alternative treatment strategy called enzyme replacement therapy; nevertheless, a significant disruption in lysosomal storage illnesses affecting the central nervous system is the blood–brain barrier. Due to the rapid advancement of fucosidosis, a rare disease, and the delay in diagnosing patients who have been identified thus far, early identification is crucial. Furthermore, the less dangerous enzyme replacement therapy shows promise.

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2026-03-25 | Cataplejía gelástica como presentación atípica de fucosidosis tipo II: primer reporte en el mundo y con nueva variante en el gen <i>FUCA1</i>

Introduccin: describimos el primer caso a nivel mundial de fucosidosis tipo II con catapleja gelstica como presentacin clnica atpica, junto con el hallazgo de una nueva variante patognica en el gen FUCA1.Descripcin del caso: paciente femenino quien a los 36 meses de edad inici con alteracin en el neurodesarrollo, talla baja, infecciones respiratorias recurrentes y angioqueratomas en manos.Adems, desde los cuatro aos present episodios transitorios de prdida de tono muscular desencadenados por la risa, compatibles con catapleja gelstica.Despus de varios aos de dar seguimiento, hasta los 16 aos, mediante secuenciacin de nueva generacin, se identific una nueva variante sin sentido en estado homocigoto descrita como NM_000147.5(FUCA1):c.551C>G(p.Ser184Ter), con lo cual se estableci el diagnstico definitivo de fucosidosis tipo II.Conclusiones: con los datos clnicos de esta paciente, se ampla el espectro fenotpico de la fucosidosis tipo II al incluir la catapleja gelstica.Este caso debe alertar para considerar ciertos datos clnicos atpicos en el diagnstico diferencial de enfermedades lisosomales, subrayando la necesidad del diagnstico molecular para resolver retos diagnsticos,

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2026-02-04 | Novel FUCA1 variants in two families, including the first report of a contiguous gene deletion syndrome involving FUCA1 and HMGCL.

Fucosidosis is a rare, autosomal recessive lysosomal storage disorder caused by deficiency of an alpha-L-fucosidase due to pathogenic variants in the FUCA1 gene, leading to the accumulation of fucoglyco-conjugates in the lysosomes of the liver, brain, skin and other organs. Its main clinical features include progressive neurological deterioration, seizures, coarse facies, visceromegaly, angiokeratoma, growth retardation, recurrent sinopulmonary infections and dysostosis multiplex. Three patients with fucosidosis from two unrelated families with severe developmental delay, hearing loss, coarse facies but no hepatosplenomegaly and angiokeratoma are presented. A homozygous, novel nonsense mutation c.236G>A (p.Trp79*) in exon 1 of the FUCA1 gene was identified in one family, and a homozygous novel 64.5 kb deletion, including HMGCL (exons 1-6), FUCA1, and CNR2 (exon 2) genes in the other. Fucosidosis should be considered in patients with delayed motor and cognitive development followed by progressive neurological deterioration, even in the absence of common features such as organomegaly and angiokeratoma. The pathogenic variants identified in both families were novel and consistent with fucosidosis type 1. To our knowledge, this is the first reported case of fucosidosis accompanied by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency resulting from a contiguous gene deletion involving the HMGCL gene at the 1p36.11 locus.

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