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Alpha-Mannosidosis - DOAJ

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Last Updated: 28 July 2022

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Mortality in patients with alpha-mannosidosis: a review of patients’ data and the literature

Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder exacerbated by reduced production of alpha-mannosidase. This research was designed to investigate the age at death and the causes of death in patients with alpha-mannosidosis who did not receive disease-modifying therapy. Median age at death for patients reported by physicians/POs was 45 years old; 53% were female. One death occurred during the patient's second decade of life, and 14 out of 15 deaths during or after the patients' third decade occurred, four of whom died in the sixth decade. Conclusions This research shows that pneumonia has been the primary cause of death in untreated patients with alpha-mannosidosis for the past 20 years, followed by cancer.

Source link: https://doi.org/10.1186/s13023-022-02422-6


Alpha-mannosidosis

Abstract: Alpha-Mannosidosis is an inherited lysosomal storage disorder that is characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual impairment. In the first year of life, some children are born with ankle equinus or develop hydrocephalus. Associated motor function disorders include muscular weakness, joint abnormalities, and ataxia. Alpha-mannosidosis is an autosomal recessive disease that is exacerbated by mutations in the MAN2B1 gene, which is found on chromosome 19. Diagnosis is made by determining acid alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed by genetic testing. The mucopolysaccharidoses are mainly related to other lysosomal storage disorders. Fluid therapy in the middle ear is often required, and the use of hearing aids is invariably necessary. To improve bodily integrity, early educational intervention is required for the growth of social skills, and physiotherapy is highly recommended. No patients appear to be completely healthy.

Source link: https://doi.org/10.1186/1750-1172-3-21


Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis

This report investigated the effects of velmanase alfa on fine and gross motor proficiency in infants and adults. Methods: Integrated Bruininks-Oseretsky test of Motor Proficiency results from velmanase alfa clinical trials was stratified by age for 14 adults and 19 children, who were treated for up to 4 years. There was a statistically significant rise in BOT-2 total point score (up by 13% from baseline to last observation in the combined adult and pediatric population. When stratified by pediatrics versus adult patients, the BOT-2 total point score in patients under BOT-2 was up 2 years in patients 18 years old compared to adults compared to adults. Following velmanase alfa treatment in pediatric patients, a qualitative review of individual BOT-2 items revealed some improvement. Pediatric patients showed stability or improvement in scaled scores relative to healthier peers, indicating that continuing skill acquisition may continue to increase autonomy and contribute to improved patient quality of life.

Source link: https://doi.org/10.1016/j.ymgmr.2020.100586


Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis

The hematopoietic stem cell transplantation was the only clinically viable therapeutic option before recently. Only in 2018 the European Medicines Agency's committee approved the recombinant enzyme velmanase alfa for long-term therapy of non-u2010neurological disorders in mild and moderate alpha-neuropathic forms of alphase alfa. The very early biochemical effects of enzyme replacement therapy in a 7-month-old patient with alpha-u2010mannosidosis were described in this research. After two months of therapy, the enzyme replacement therapy was found to reduce the content of three distinct mannosylu2010oligosaccharides tested by tandem mass spectrometry. In the following points of observation, the study also showed that the enzymatic activity in serum 1 week after the first infusion was four times higher than the normal values and constant. These findings led us to believe that velmanase alfa could be biologically active in this young patient.

Source link: https://doi.org/10.1002/jmd2.12144


The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis

SPARKLE is an alpha-mannosidosis registry that aims to gather long-term safety and effectiveness data on the use of velmanase alfa in everyday medical care in patients with alpha-mannosidosis. Results The SPARKLE registry is a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis that will begin in 2020, with patient registration starting in 2020. The primary success measure is a global treatment response rate, which is determined as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality-of-life clinical studies; secondary effectiveness studies are used to characterize the patient population with alpha-mannosidosis with respect to clinical manifestation, evolution, and natural history of the disease. Any patient in the European Union with an alpha-mannosidosis diagnosis who is able to participate would likely be eligible for enrollment in the registry.

Source link: https://doi.org/10.1186/s13023-020-01549-8


Intellectual functioning in alpha‐mannosidosis

Patients have particular physical and developmental characteristics, but no evidence regarding patient-specific cognitive functioning has been published. Here we provide cognitive ability scores on 12 patients with alpha-u2010mannosidosis. Patients with alpha2010mannosidosis have various degrees of intellectual impairment, but not with age, particularly in the first decade of life, according to the initial and pooled studies. Patients treated with hematopoietic stem cell transplantation tend to have stable cognitive skills.

Source link: https://doi.org/10.1002/jmd2.12073


Long-term outcome of patients with alpha-mannosidosis – A single center study

The aim of this report was to report the long-term follow-up of 12 Polish patients with AM, evaluate the clinical, biochemical, and molecular findings, as well as disease progression. In ten patients, the hearing loss, which was one of the first signs, was present in childhood. The mean age at AM diagnosis was 6 years, while the median was 4 years old. p. m. The most common variant in the MAN2B1 gene was c. 2245C > T, p. m. Following birth, children with AM increase slowly, eventually reaching the 3rd percentile. In all patients, hearing loss was not progressive, although a gradual onset of intellectual impairment with no developmental regression was observed. Conclusions: Our study found the sensorineural hearing loss as one of the first reported signs of AM, which was congenital and non-progressive during the normal course of disease.

Source link: https://doi.org/10.1016/j.ymgmr.2021.100826


Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice

Alpha-mannosidosis is a glycoproteinosis triggered by a deficiency of lysosomal acid alpha-mannosidase, which principally affects central nervous system neurons, and causes pathognomonic intellectual dysfunction in the clinical condition. Long-term delivery of recombinant human enzymes was used to determine the effects of enzyme replacement therapy by immunogenically impaired mice. According to biochemical results, hippocampus may be one of the brain structures that benefit the most from long-term ERT. Following mid-term and long-term therapy, long-term ERT reduced primary substrate storage and neuroinflammation in the hippocampus, as well as increased spatial learning. And long-ERT did not recover cognitive skills to the same as healthy mice, according to detailed reports of spatial memory and spatial-cognitive results, even after extensive ERT did not restore cognitive skills to the same level as healthy mice. These studies show that long-term ERT can provide promise not only for alpha-mannosidosis' somatic defects but also to reduce cognitive impairments of the disease.

Source link: https://doi.org/10.1016/j.nbd.2017.07.013


Alpha-Mannosidosis: Therapeutic Strategies

In alpha-mannosidosis, there is no association between genotype and phenotype in other lysosomal storage disorders. Enzyme replacement therapy is currently the most effective treatment for lysosomal storage disease, including alpha-mannosidosis. The most important reason to provide hematopoietic stem cell transplantation in patients affected by alpha-mannosidosis is to maintain neurocognitive function and avoidance of premature death. The results obtained from a Phase I–IIII research and a Phase III research point to the recombinant enzyme's positive clinical effects in patients with alpha-mannosidosis.

Source link: https://doi.org/10.3390/ijms19051500


Health Related Quality of Life, Disability, and Pain in Alpha Mannosidosis

The purpose of this review, based on the Childhood Health Assessment Questionnaire and the EuroQol 5 Dimension 5 Level Questionnaire in patients with alpha-mannosidosis participating in rhLAMAN-10, a phase III open-label clinical trial of recombinant human lysosomal alpha-mannosidase, was to determine disability, pain, and overall health. Patients receiving up to 48 months of velmanase alfa therapy show improvement in health-related quality of life and a decrease in disability and pain in patients receiving up to 48 months of EQ-5D-5L therapy.

Source link: https://doi.org/10.1177/2326409818796854

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions