Clinical features of mannosidosis

Autio, S.

doi:10.1016/s0022-3476(75)80503-8

Cited by 17 publications

(27 citation statements)

References 4 publications

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“…Similarly in hepatocytes derived from a child with α-mannosidosis (Gordon et al 1980), mitochondria were abnormal with respect to their size and shape, however, their internal structure was not changed. In contrast to our results on fibroblasts and Gordon et al (1980) on hepatocytes, two other studies did not report any mitochondrial changes at ultrastructure level in α-mannosidosis patients either on hepatocytes or brain tissue obtained at autopsy (Desnick et al 1976;Autio et al 1982). Unfortunately, mutation types were not described in these patients.…”

Section: Discussioncontrasting

confidence: 99%

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Ultrastructural and functional abnormalities of mitochondria in cultivated fibroblasts from α-mannosidosis patients

et al. 2009

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α-Mannosidosis is a lysosomal storage disorder caused by α-mannosidase deficiency. Clinical course of the disease ranges from severe infantile to milder juvenile type and includes mental retardation, skeletal deformities, coarse facies, hepatomegaly and hearing loss. The aim of the study was to analyse mitochondrial ultrastructure and function in cultivated fibroblasts from three patients with α-mannosidosis. All patients were homozygous for the c.2248C>T mutation in the MAN2B1 gene encoding lysosomal α-mannosidase. The mutation results in incorrect protein folding and severe decrease of α-mannosidase activity. The misfolded protein is retained by the control system of endoplasmic reticulum (ER). In analysed fibroblasts, we observed dilated ER, higher amount of aberrant mitochondria and reduced mitochondrial mass compared to controls. Respiratory chain complex IV, cytochrome c oxidase (COX), activity and the ratio between COX and citrate synthase (control enzyme) were significantly increased in comparison to controls (P < 0.05). Furthermore, the activity at least from one of other respiratory chain complexes was increased in each studied cell line. Mitochondrial membrane potential as well as reactive oxygen species production were comparable with controls. Based on our results, we hypothesize more profound effect of swelled and damaged mitochondria and ER dilatation on tissues with higher energy demand than fibroblasts have.

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Section: Discussioncontrasting

confidence: 99%

“…Many patients suffer from neuromotor disabilities and ataxia. Neurocognitive defects have been described in all α-mannosidosis children, but the age of onset, severity and progression of the disease are variable, unpredictable (Autio et al 1982;Noll et al 1989;Grewal et al 2004) and may further deteriorate with age (Shapiro et al 1995).…”

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confidence: 99%

Ultrastructural and functional abnormalities of mitochondria in cultivated fibroblasts from α-mannosidosis patients

et al. 2009

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“…A continuum of clinical severity is observed between type I (infantile onset), with symptoms usually occurring before the age of 12 months with progressive deterioration and death between 3 and 12 years of age, and type II (juvenile onset) with milder symptoms and normal life expectancy. 1,4,5 Enzyme replacement therapy is currently not available for a-mannosidosis as it is for other lysosomal storage disorders like Gaucher disease type I and Fabry's disease. 6,7 Bone marrow transplantation (BMT) has been shown to lead to stabilization of neurological function in some lysosomal storage diseases such as mucopolysaccharidosis type I-H (M. Hurler).…”

Section: Discussionmentioning

confidence: 99%

T-cell-depleted peripheral blood stem cell transplantation for α-mannosidosis

Albert

Schuster

Peters

et al. 2003

Bone Marrow Transplant

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Section: Introductionmentioning

confidence: 99%

“…Many patients develop neuromotor disabilities and ataxia (Autio et al, 1982), as well as hearing impairments that affect receptive language abilities (Noll et al, 1989). Neurocognitive defects have been described in all children with ␣-mannosidosis, but severity, age of onset, and progression are variable and unpredictable (Autio et al, 1982). Visuomotor integration and other neurocognitive domains are affected (Noll et al, 1989;Grewal et al, 2004) and may further deteriorate with age (Shapiro et al, 1995;Grewal et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Neurocognitive and Psychotiform Behavioral Alterations and Enhanced Hippocampal Long-Term Potentiation in Transgenic Mice Displaying Neuropathological Features of Human α-Mannosidosis

D’Hooge¹,

Lüllmann‐Rauch²,

Beckers³

et al. 2005

J. Neurosci.

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Mice with ␣-mannosidase gene inactivation provide an experimental model for ␣-mannosidosis, a lysosomal storage disease with severe neuropsychological and psychopathological complications. Neurohistological alterations in these mice were similar to those in patients and included vacuolations and axonal spheroids in the CNS and peripheral nervous system. Vacuolation was most prominent and evenly distributed in neuronal perikarya of the hippocampal CA2 and CA3 regions, whereas CA1 and dentate gyrus were weakly or not affected. Field potential recordings from CA1 region in hippocampal slices showed enhanced theta burst-induced long-term potentiation (LTP) in ␣-mannosidase-deficient mice. Longitudinal assessment in age-matched ␣-mannosidase-deficient and wild-type littermates, using an extended test battery, demonstrated a neurocognitive and psychotiform profile that may relate to the psychopathological alterations in clinical ␣-mannosidosis. Brainstem auditory-evoked potentials and basic neuromotor abilities were not impaired and did not deteriorate with age. Exploratory and conflict tests revealed consistent decreases in exploratory activity and emotional blunting in the knock-out group. ␣-Mannosidosis mice were also impaired in aversively motivated learning and acquisition of signal-shock associations. Acquisition and reversal learning in the water maze task, passive avoidance learning in the step-through procedure, as well as emotional response conditioning in an operant procedure were all impaired. Acquisition or shaping of an appetitive instrumental conditioning task was unchanged. Appetitive odor discrimination learning was only marginally impaired during shaping, whereas both the discrimination and reversal subtasks were normal. We propose that prominent storage and enhanced LTP in hippocampus have contributed to these specific behavioral alterations in ␣-mannosidase-deficient mice.

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Clinical features of mannosidosis

Cited by 17 publications

References 4 publications

Ultrastructural and functional abnormalities of mitochondria in cultivated fibroblasts from α-mannosidosis patients

Ultrastructural and functional abnormalities of mitochondria in cultivated fibroblasts from α-mannosidosis patients

T-cell-depleted peripheral blood stem cell transplantation for α-mannosidosis

Neurocognitive and Psychotiform Behavioral Alterations and Enhanced Hippocampal Long-Term Potentiation in Transgenic Mice Displaying Neuropathological Features of Human α-Mannosidosis

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