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Jürgen W. Spranger - One of the best experts on this subject based on the ideXlab platform.

  • Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTA) in a patient with Mucolipidosis II induces changes in the size and cellular distribution of GNPTG.
    Human Mutation, 2006
    Co-Authors: Stephan Tiede, Jürgen W. Spranger, Michael Cantz, Thomas Braulke
    Abstract:

    Mucolipidosis type II (ML II; I-cell disease) and Mucolipidosis III (ML III; pseudo Hurler polydystrophy) are autosomal recessively inherited disorders caused by a defective N-acetylglucosamine 1-phosphotransferase (phosphotransferase). The formation of mannose 6-phosphate markers in soluble lysosomal enzymes is impeded leading to their increased excretion into the serum, to cellular deficiency of multiple hydrolases, and lysosomal storage of non-digested material. Phosphotransferase deficiency is caused by mutations in GNPTA and GNPTG encoding phosphotransferase subunits. Here we report on an adolescent with progressive joint contractions and other signs of Mucolipidosis II who survived to the age of 14 years. Impaired trafficking of lysosomal enzymes cathepsin D and -hexosaminidase in metabolically labeled fibroblasts was documented. Mutations in the GNPTG gene and alterations in the GNPTG mRNA level were not detected. A different electrophoretic mobility of the 97 kDa GNPTG dimer suggested posttranslational modification abrogating the compartmentalization of GNPTG in the Golgi apparatus. A nucleotide substitution in the GNPTA gene (c.3707A>T) was identified altering the predicted C-terminal transmembrane anchor of the phosphotransferase subunit. The data demonstrate that defective GNPTA not only impairs lysosomal enzyme targeting but also the availability of intact GNPTG required for phosphotransferase activity and assembly of subunits. © 2006 Wiley-Liss, Inc.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as Pacman dysplasia.
    American journal of medical genetics. Part A, 2005
    Co-Authors: Robert A. Saul, Harold A. Taylor, Virginia K. Proud, Jules G. Leroy, Jürgen W. Spranger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports. © 2005 Wiley-Liss, Inc.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as pacman dysplasia. Discussion
    American Journal of Medical Genetics, 2005
    Co-Authors: Robert A. Saul, Jürgen W. Spranger, Harold A. Taylor, Ralph S. Lachman, Virginia K. Proud, Jules G. Leroy, William R. Wilcox, David L. Rimoin, David A. Wenger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports.

Harold A. Taylor - One of the best experts on this subject based on the ideXlab platform.

  • Mucolipidosis III (pseudo Hurler polydystrophy): cytological and ultrastructural observations of cultured fibroblast cells
    Clinical Genetics, 2008
    Co-Authors: Harold A. Taylor, George H. Thomas, Carol S. Miller, Thaddeus E. Kelly, D. Siggers
    Abstract:

    Cultured fibroblast cells from four patients with Mucolipidosis III (pseudo-Hurler polydystrophy) were examined by phase contrast, dark-field and electron microscopy. Both phase and dark-field microscopy revealed striking abnormalities in three of these patients which were indistinguishable from those seen in Mucolipidosis II (I-cell disease). While electron microscopy indicated that the structural alterations found in both Mucolipidosis II and III may he due to an increased storage of material within the cytoplasm, clear differences in the ultrastructural morphology were detectable between the two disorders.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as Pacman dysplasia.
    American journal of medical genetics. Part A, 2005
    Co-Authors: Robert A. Saul, Harold A. Taylor, Virginia K. Proud, Jules G. Leroy, Jürgen W. Spranger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports. © 2005 Wiley-Liss, Inc.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as pacman dysplasia. Discussion
    American Journal of Medical Genetics, 2005
    Co-Authors: Robert A. Saul, Jürgen W. Spranger, Harold A. Taylor, Ralph S. Lachman, Virginia K. Proud, Jules G. Leroy, William R. Wilcox, David L. Rimoin, David A. Wenger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports.

Robert A. Saul - One of the best experts on this subject based on the ideXlab platform.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as Pacman dysplasia.
    American journal of medical genetics. Part A, 2005
    Co-Authors: Robert A. Saul, Harold A. Taylor, Virginia K. Proud, Jules G. Leroy, Jürgen W. Spranger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports. © 2005 Wiley-Liss, Inc.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as pacman dysplasia. Discussion
    American Journal of Medical Genetics, 2005
    Co-Authors: Robert A. Saul, Jürgen W. Spranger, Harold A. Taylor, Ralph S. Lachman, Virginia K. Proud, Jules G. Leroy, William R. Wilcox, David L. Rimoin, David A. Wenger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports.

Raphael Schiffmann - One of the best experts on this subject based on the ideXlab platform.

  • Unique molecular signature in Mucolipidosis type IV microglia.
    Journal of neuroinflammation, 2019
    Co-Authors: Antony Cougnoux, Raphael Schiffmann, Rebecca A. Drummond, Mason Fellmeth, Fatemeh Navid, Amanda L. Collar, James R. Iben, Ashok B. Kulkarni, James Pickel, Christopher A. Wassif
    Abstract:

    Lysosomal storage diseases (LSD) are a large family of inherited disorders characterized by abnormal endolysosomal accumulation of cellular material due to catabolic enzyme and transporter deficiencies. Depending on the affected metabolic pathway, LSD manifest with somatic or central nervous system (CNS) signs and symptoms. Neuroinflammation is a hallmark feature of LSD with CNS involvement such as Mucolipidosis type IV, but not of others like Fabry disease. We investigated the properties of microglia from LSD with and without major CNS involvement in 2-month-old Mucolipidosis type IV (Mcoln1−/−) and Fabry disease (Glay/−) mice, respectively, by using a combination of flow cytometric, RNA sequencing, biochemical, in vitro and immunofluorescence analyses. We characterized microglia activation and transcriptome from Mucolipidosis type IV and Fabry disease mice to determine if impaired lysosomal function is sufficient to prime these brain-resident immune cells. Consistent with the neurological pathology observed in Mucolipidosis type IV, Mcoln1−/− microglia demonstrated an activation profile with a mixed neuroprotective/neurotoxic expression pattern similar to the one we previously observed in Niemann-Pick disease, type C1, another LSD with significant CNS involvement. In contrast, the Fabry disease microglia transcriptome revealed minimal alterations, consistent with the relative lack of CNS symptoms in this disease. The changes observed in Mcoln1−/− microglia showed significant overlap with alterations previously reported for other common neuroinflammatory disorders including Alzheimer’s, Parkinson’s, and Huntington’s diseases. Indeed, our comparison of microglia transcriptomes from Alzheimer’s disease, amyotrophic lateral sclerosis, Niemann-Pick disease, type C1 and Mucolipidosis type IV mouse models showed an enrichment in “disease-associated microglia” pattern among these diseases. The similarities in microglial transcriptomes and features of neuroinflammation and microglial activation in rare monogenic disorders where the primary metabolic disturbance is known may provide novel insights into the immunopathogenesis of other more common neuroinflammatory disorders. ClinicalTrials.gov, NCT01067742, registered on February 12, 2010

  • ARTICLE
    2015
    Co-Authors: Cheng-chang Chen, Raphael Schiffmann, Marco Keller, Martin Hess, Nicole Urban, Annette Wolfgardt, Michael Schaefer, Franz Bracher, Martin Biel, Christian Wahl-schott
    Abstract:

    A small molecule restores function to TRPML1 mutant isoforms responsible for Mucolipidosis type I

  • Noninvasive diagnosis and ophthalmic features of Mucolipidosis type IV.
    Ophthalmology, 2002
    Co-Authors: Janine A. Smith, Ehud Goldin, Chi-chao Chan, Raphael Schiffmann
    Abstract:

    Abstract Objective To comprehensively describe the ophthalmic characteristics of patients with Mucolipidosis type IV. Design Prospective natural history study. Participants Twenty-two patients with confirmed Mucolipidosis type IV. Methods or testing External and slit-lamp examination with dilated funduscopy, photography of corneal and retinal lesions, and exfoliative conjunctival cytology were performed. Main outcome measures Grading of corneal, optic nerve, retinal vasculature, and pigmentary abnormalities. Results All patients exhibited some degree of corneal epithelial haze, optic nerve pallor, retinal vascular attenuation, and retinal pigment epithelial changes. The associated ocular findings observed in decreasing order of frequency were strabismus, corneal erosion, cataract, corneal abnormalities, fundus abnormalities, and ptosis. The older patients were significantly more likely to demonstrate severe optic nerve pallor, retinal vascular attenuation, and corneal epithelial haze. Conjunctival cytologic studies showed characteristic lysosomal inclusions on light and electron microscopy. Conclusions Patients with Mucolipidosis type IV have characteristic ophthalmic features, most of which have a progressive course. Conjunctival cytologic studies help confirm the diagnosis of this disorder.

  • Mucolipidosis type IV Characteristic MRI findings
    Neurology, 1998
    Co-Authors: K. P. Frei, Nicholas J. Patronas, K. E. Crutchfield, Gheona Altarescu, Raphael Schiffmann
    Abstract:

    Objective: The objective of this study is to characterize the brain abnormalities on head MRI of patients with Mucolipidosis type IV. Background: Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology. Patients develop corneal clouding, retinal degeneration, spastic quadriparesis, and mental retardation. Patients with this disorder have not been studied systematically. Methods: We studied prospectively 15 consecutive patients with Mucolipidosis type IV using cranial MRI. Results: Fourteen patients with these typical clinical findings had a hypoplastic corpus callosum with absent rostrum and a dysplastic or absent splenium, signal abnormalities on T1-weighted head MRI images in the white matter, and increased ferritin deposition in the thalamus and basal ganglia. Atrophy of the cerebellum and cerebrum was observed in older patients, which may reflect disease progression. One patient with a mild clinical variant had a normal corpus callosum. Conclusion: Patients with Mucolipidosis type IV have characteristic cranial MRI findings that suggest that this disorder causes both developmental and neurodegenerative abnormalities.

Jules G. Leroy - One of the best experts on this subject based on the ideXlab platform.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as Pacman dysplasia.
    American journal of medical genetics. Part A, 2005
    Co-Authors: Robert A. Saul, Harold A. Taylor, Virginia K. Proud, Jules G. Leroy, Jürgen W. Spranger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports. © 2005 Wiley-Liss, Inc.

  • Prenatal Mucolipidosis type II (I-cell disease) can present as pacman dysplasia. Discussion
    American Journal of Medical Genetics, 2005
    Co-Authors: Robert A. Saul, Jürgen W. Spranger, Harold A. Taylor, Ralph S. Lachman, Virginia K. Proud, Jules G. Leroy, William R. Wilcox, David L. Rimoin, David A. Wenger
    Abstract:

    Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with Mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of Mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML-II) in other published reports.