Biochemical studies on a case of feline mannosidosis.
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ABSTRACT:
SUBMITTER: Burditt LJ
PROVIDER: S-EPMC1162026 | biostudies-other | 1980 Sep
REPOSITORIES: biostudies-other
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Project description:Two homologous series of urinary oligosaccharides were identified by h.p.l.c. and fast-atom-bombardment mass spectrometry in feline alpha-mannosidosis. The predominant series has the composition Man2-8GlcNAc2 and a minor series the composition Man2-9GlcNAc. The structure of the most abundant oligosaccharide, which accounts for over 80% of the urinary oligosaccharide, was shown to be alpha-D-Manp(1----3)[alpha-D-Manp-(1----6)]beta-D-Manp -(1----4)-beta-D-GlcpNA c-(1----4)-D-GlcNAc by gas chromatography and mass spectrometry. Such a structure is consistent with the incomplete catabolism of complex N-linked glycans due to a deficiency of alpha-D-mannosidase in tissue lacking an endohexosaminidase activity.
| S-EPMC1153114 | biostudies-other
Project description:One hundred and sixty-six cats from two animal shelters were subjected to enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence antibody test (IFAT), conventional polymerase chain reaction (cPCR), quantitative PCR (qPCR) and parasitological tests (PA) for the diagnosis of Leishmania spp. Among them, 15% (25/166), 53.6% (89/166), 3.6% (06/166) and 1.8% (03/166) were positive by ELISA, IFAT, both PCRs and PA, respectively. The sequencing of ITS-1 PCR amplicons revealed a 100% match with Leishmania infantum. After the Leishmania spp. survey, 12 cats were selected and divided into two groups for clinical, hematological, and biochemical analysis: six L. infantum positive cats (G1) and six Leishmania spp. negative cats (G2). All the cats were negative for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). A statistical analysis indicated significantly low platelet counts and significant hyperproteinemia associated with hypoalbuminemia in positive cats (p<0.05). Our results suggest that in endemic areas, cats with clinical signs of feline leishmaniosis (such as skin lesions, weight loss and/or enlarged lymph nodes) and that exhibit hematological and biochemical changes, such as low platelet counts and hyperproteinemia with hypoalbuminemia, should be tested for Leishmania spp. infection.
| S-EPMC10321720 | biostudies-literature
Project description:Alpha mannosidosis is an ultrarare pathology with variable phenotypic manifestations, characterized by the deficiency of lysosomal alpha mannosidase which causes accumulation of neutral oligosaccharides. Until recently, the hematopoietic stem cell transplantation was the only clinical feasible therapeutic option. Only in 2018, the European Medicines Agency's committee approved the recombinant enzyme velmanase alfa for long-term treatment of non-neurological manifestations in mild and moderate forms of alpha-mannosidosis. In this study, the very early biochemical effects of enzyme replacement therapy in in a 7-month-old patient with alpha-mannosidosis were described. Velmanase alpha was administered as supporting therapy awaiting for hematopoietic stem cell transplantation, the treatment chosen for the patient because of the early onset form. The results showed that the enzyme replacement therapy was able to reduce the content of three different mannosyl-oligosaccharides monitored by tandem mass spectrometry after 2?months of treatment. In particular, the mean relative changes from baseline values were -67% in urine and -53% in serum at the latest observation. The study also showed that the enzymatic activity detected in serum 1?week after the first infusion was four times higher than the normal values and constant in the following points of observation. These findings led us to assume that velmanase alfa might be biologically active in this young patient.
| S-EPMC7463052 | biostudies-literature
Project description:Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual disability. It occurs in approximately 1 of 500,000 live births. The children are often born apparently normal, and their condition worsens progressively. Some children are born with ankle equinus or develop hydrocephalus in the first year of life. Main features are immune deficiency (manifested by recurrent infections, especially in the first decade of life), skeletal abnormalities (mild-to-moderate dysostosis multiplex, scoliosis and deformation of the sternum), hearing impairment (moderate-to-severe sensorineural hearing loss), gradual impairment of mental functions and speech, and often, periods of psychosis. Associated motor function disturbances include muscular weakness, joint abnormalities and ataxia. The facial trait include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, and prognathism. Slight strabismus is common. The clinical variability is significant, representing a continuum in severity. The disorder is caused by lysosomal alpha-mannosidase deficiency. Alpha-mannosidosis is inherited in an autosomal recessive fashion and is caused by mutations in the MAN2B1 gene located on chromosome 19 (19 p13.2-q12). Diagnosis is made by measuring acid alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed by genetic testing. Elevated urinary secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic. Differential diagnoses are mainly the other lysosomal storage diseases like the mucopolysaccharidoses. Genetic counseling should be given to explain the nature of the disease and to detect carriers. Antenatal diagnosis is possible, based on both biochemical and genetic methods. The management should be pro-active, preventing complications and treating manifestations. Infections must be treated frequently. Otolaryngological treatment of fluid in the middle ear is often required and use of hearing aids is invariably required. Early educational intervention for development of social skills is needed and physiotherapy is important to improve bodily function. Orthopedic surgery may be necessary. The long-term prognosis is poor. There is an insidiously slow progression of neuromuscular and skeletal deterioration over several decades, making most patients wheel-chair dependent. No patients manage to be completely socially independent. Many patients are over 50 years of age.
| S-EPMC2515294 | biostudies-literature
Project description:Analysis of the neutral urinary oligosaccharides in bovine, feline and human mannosidosis by thin-layer and gel-permeation chromatography has shown that the patterns of stored oligosaccharides in the three species are different. In bovine and feline mannosidosis the most abundant urinary oligosaccharide is also the most abundant in the tissues of each species. The predominant oligosaccharides were purified by a combination of gel-filtration, ion-exchange and thin-layer chromatography and shown to contain only mannose and N-acetylglucosamine by g.l.c. and g.l.c.--mass spectrometry. The probable composition and size of each oligosaccharide were predicted from its chromatographic properties, sugar composition and the known structure of asparagine-linked oligosaccharides. The bovine and feline oligosaccharides belonged to a homologous series of general composition Mann (GlcNAc)2, whereas the human oligosaccharides belong to a different series, MannGlcNAc. These structures suggest that lysosomal endohexosaminidase is not present in bovine and feline tissues. The predominant feline storage product, Man3(GlcNAc)2, was the expected storage product from the catabolism of complex asparagine-linked glycans. In contrast, the predominant bovine oligosaccharide, Man2(GlcNAc)2, probably lacks one of the alpha-linked mannose residues in the core region. A similar situation occurs in human mannosidosis. It is predicted that in these species either that the residual mutant alpha-D-mannosidase retains activity towards one of the core alpha-linked mannose residues or that another form of lysosomal alpha-D-mannosidase that is unaffected in these disorders occurs. It is concluded that the differences in storage products are due to differences in the catabolic pathways of glycoproteins among the species.
| S-EPMC1152438 | biostudies-other
Project description:CaseA 34-year-old woman was referred to our hospital with progressive movement disorders and neurodegeneration with brain iron accumulation and enlargement of the frontal diploe on the MRI. Metabolic testing revealed that she had α-mannosidosis (AMD), a lysosomal storage disorder.BackgroundAMD is a rare genetic disorder that causes α-mannosidase deficiency resulting in lysosomal accumulation of undigested oligosaccharides. The symptoms of AMD consist of facial and skeletal deformities combined with progressive psychiatric and neurological complaints, especially ataxia and mental retardation. Bilateral patellar dislocation and hearing impairment are frequent.DiscussionThe movement disorders we found in our patient have not been reported previously, but they are likely late symptoms of this progressive disorder. The iron deposits in the basal ganglia have also not been reported in AMD and are yet of unknown significance. Lysosomal storage disorders, such as AMD, should be considered in patients with progressive neurologic conditions and neurodegeneration with brain iron accumulation on MRI.
| S-EPMC3509898 | biostudies-literature
Project description:BackgroundDeficiency in the enzyme β-mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood-onset β-mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available.MethodsWe report 2-year outcomes following the first umbilical cord blood transplant in a 4-year-old boy with early childhood-onset disease.ResultsWe show restoration of leukocyte β-mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β-mannosidase activity and dramatic decrease in urine-free oligosaccharides were also observed. MRI of the brain remained stable. Neurocognitive evaluation revealed test point gains, although the magnitude of improvement was less than expected for age, causing lower IQ scores that represent a wider developmental gap between the patient and unaffected peers.ConclusionOur findings suggest that hematopoietic cell transplant can correct the biochemical defect in β-mannosidosis, although preservation of the neurocognitive trajectory may be a challenge.
| S-EPMC6625138 | biostudies-literature
Project description:β-mannosidosis is a rare autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of β-mannosidase. Clinical presentation includes intellectual deficits, hearing loss, and recurrent respiratory infections. This report describes the dental treatment and follow-up dental care of a child with β-mannosidosis. The patient presented to the dental clinic at the age of 6 years with a localized swelling of his lower posterior teeth. Sickle cell disease and physical and mental developmental delays were noted. Clinical examination revealed a flattened nasal bridge, large head, short neck, open bite, gingival overgrowth, macroglossia, enlarged pulp chambers, and poor oral hygiene. Surgical treatment under general anesthesia included extractions, pulp therapy, and restorations. Four years later, the child returned with generalized gingival inflammation and new carious lesions. Periodontal and restorative treatment was provided, and a preventive dental regimen was established. Mannosidosis cases require complex dental procedures, consultations, and prompt follow-up.
| S-EPMC8679027 | biostudies-literature
Project description:Alpha-mannosidosis (?-mannosidosis) is a rare lysosomal storage disorder with an autosomal recessive inheritance caused by mutations in the gene encoding for the lysosomal ?-d-mannosidase. So far, 155 variants from 191 patients have been identified and in part characterized at the biochemical level. Similarly to other lysosomal storage diseases, there is no relationship between genotype and phenotype in alpha-mannosidosis. Enzyme replacement therapy is at the moment the most effective therapy for lysosomal storage disease, including alpha-mannosidosis. In this review, the genetic of alpha-mannosidosis has been described together with the results so far obtained by two different therapeutic strategies: bone marrow transplantation and enzyme replacement therapy. The primary indication to offer hematopoietic stem cell transplantation in patients affected by alpha-mannosidosis is preservation of neurocognitive function and prevention of early death. The results obtained from a Phase I?II study and a Phase III study provide evidence of the positive clinical effect of the recombinant enzyme on patients with alpha-mannosidosis.
| S-EPMC5983820 | biostudies-literature
Project description:Pythiosis is frequently reported in dogs and horses inhabiting tropical, subtropical and temperate areas of the USA, but the disease is rare in domestic cats. The clinical presentation of feline pythiosis includes subcutaneous masses without ulcerated tissue and involvement of the intestinal tract. Here in we report an eight-week-old female unvaccinated stray kitten with an unusual extensive circular ulcerated lesion on her left flank. The lesion did not respond favorably to administration of systemic antibiotics. Clinical specimens submitted for culture demonstrated submerged fungal-like flat colonies later identified as Pythium insidiosum, a finding also confirmed by histopathology, serology, and DNA sequencing and thus, treated with itraconazole. Since no improvement was observed, Pythium-immunotherapy was initiated. The cat responded to the latter approach and in less than 10 days, the lesion had contracted around the edges and was crusting off to reveal healthy granulation tissue. Twenty-three days after immunotherapy was initiated the original wound had shrunken significantly to a small scabbed area. However, the cat acutely developed tachypnea, lung and intestinal complications and due to her rapid deterioration, humane euthanasia was elected. Unfortunately, necropsy was not conducted. The clinical presentation reported here suggests large ulcerative cutaneous lesions caused by P. insidiosum can also occur in domestic cats. Despite reports of unsuccessful treatment results of feline pythiosis using Pythium-immunotherapy, this report suggests this approach might be helpful in similar feline cases.
| S-EPMC6849338 | biostudies-literature