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Revista Medica de Chile Mar 2003We report a female newborn with type II mucolipidoses. This condition is characterized clinically by Hurler like features, progressive psychomotor retardation and death...
We report a female newborn with type II mucolipidoses. This condition is characterized clinically by Hurler like features, progressive psychomotor retardation and death during the first or second year of life. Most cases present during the first year of life, with poor weight gain and coarse facies features. The cause of this rare autosomal recessive hereditary disease is the deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase, required for the synthesis of mannose-6-phosphate, the ligand that allows the transport of acid hydrolases into lysosomes. The patient had clinical features commonly found in mucolipidosis II, including disproportionate dwarfism, retarded psychomotor development, coarse facies features, gibbous and restricted joint mobility. The diagnosis was proved by an extremely elevated activity of lysosomal enzymes in the serum, secondary to non-regulated secretion and subsequent intracellular depletion of these proteins. The child suffered recurrent pneumonia and died at 22 months of age.
Topics: Female; Glycosaminoglycans; Hexosaminidases; Humans; Infant, Newborn; Lysosomes; Mucolipidoses; Radiography; Spine
PubMed: 12790082
DOI: No ID Found -
Revista Medica de Chile Jul 2008We report a 7 year-old girl with mapuche ancestors, diagnosed as a cerebral palsy since infancy and on active rehabilitation. She acquired motor and cognitive skills at...
We report a 7 year-old girl with mapuche ancestors, diagnosed as a cerebral palsy since infancy and on active rehabilitation. She acquired motor and cognitive skills at 3 years of age. At 5 years of age, a slow neurological deterioration started, associated to visual impairment. Optic atrophy was added to the typical neurological exam of ataxic cerebral palsy and the diagnosis was re-considered. Neuroimaging showed a slow and progressive atrophy of intracerebral structures and ultramicroscopy revealed intracytoplasmatic inclusions in conjunctiva and skin, compatible with mucolipidoses type IV (ML-IV). ML-IV must be included in the differential diagnosis of cerebral palsy associated with loss of acquired skills and progressive visual impairment. Electron microscopy of skin or conjunctiva is a useful diagnostic test. Suspicion of ML-IV must not be restricted to Ashkenazi Jewish population.
Topics: Cerebral Palsy; Child; Chile; Diagnosis, Differential; Female; Humans; Indians, South American; Magnetic Resonance Spectroscopy; Mucolipidoses
PubMed: 18949166
DOI: No ID Found -
Journal of Inherited Metabolic Disease Apr 2008Modification of the carbohydrate chains of soluble lysosomal enzymes with mannose 6-phosphate residues is a prerequisite for their mannose 6-phosphate receptor-dependent... (Review)
Review
Modification of the carbohydrate chains of soluble lysosomal enzymes with mannose 6-phosphate residues is a prerequisite for their mannose 6-phosphate receptor-dependent transport to lysosomes. GlcNac-1-phosphotransferase localized in the Golgi apparatus represents a hexameric alpha(2)beta(2)gamma(2) subunit complex and plays a key role in the formation of the mannose 6-phosphate recognition marker. Defects in the GlcNac-1-phosphotransferase complex cause two diseases, mucolipidosis type II and III, which are characterized by missorting and cellular loss of lysosomal enzymes, and lysosomal accumulation of storage material. The recent identification of two genes, GNPTAB and GNPTG, encoding the three subunits of GlcNac-1-phosphotransferase leads to an improvement of both pre- and postnatal diagnosis of affected individuals, and permits the analysis of structural requirements for efficient formation of mannose 6-phosphate residues on lysosomal enzymes. The alpha/beta subunits precursor matures by proteolytic cleavage and contains the catalytic activity as well as the capability to recognize lysosomal enzymes. The role of the gamma-subunits for activity, stability and oligomerization of the GlcNac-1-phosphotransferase subunits is still unclear.
Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Lysosomes; Mucolipidoses; Mutation; Phenotype; Protein Conformation; Structure-Activity Relationship; Substrate Specificity; Transferases (Other Substituted Phosphate Groups)
PubMed: 18425436
DOI: 10.1007/s10545-008-0862-5 -
Laboratornoe Delo 1990
Review
Topics: Genetics, Medical; Humans; Mucolipidoses; Mucopolysaccharidoses
PubMed: 1705591
DOI: No ID Found -
European Journal of Cell Biology Jan 2010Lysosomal hydrolases catalyze the degradation of a variety of macromolecules including proteins, carbohydrates, nucleic acids and lipids. The biogenesis of lysosomes or... (Review)
Review
Lysosomal hydrolases catalyze the degradation of a variety of macromolecules including proteins, carbohydrates, nucleic acids and lipids. The biogenesis of lysosomes or lysosome-related organelles requires a continuous substitution of soluble acid hydrolases and lysosomal membrane proteins. The targeting of lysosomal hydrolases depends on mannose 6-phosphate residues (M6P) that are recognized by specific receptors mediating their transport to an endosomal/prelysosomal compartment. The key role in the formation of M6P residues plays the GlcNAc-1-phosphotransferase localized in the Golgi apparatus. Two genes have been identified recently encoding the type III alpha/beta-subunit precursor membrane protein and the soluble gamma-subunit of GlcNAc-1-phosphotransferase. Mutations in these genes result in two severe diseases, mucolipidosis type II (MLII) and III (MLIII), biochemically characterized by the missorting of multiple lysosomal hydrolases due to impaired formation of the M6P recognition marker, and general lysosomal dysfunction. This review gives an update on structural properties, localization and functions of the GlcNAc-1-phosphotransferase subunits and improvements of pre- and postnatal diagnosis of ML patients. Further, the generation of recombinant single-chain antibody fragments against M6P residues and of new mouse models of MLII and MLIII will have considerable impact to provide deeper insight into the cell biology of lysosomal dysfunctions and the pathomechanisms underlying these lysosomal disorders.
Topics: Animals; Disease; Health; Humans; Mannose; Mucolipidoses; Phosphorylation; Transferases (Other Substituted Phosphate Groups)
PubMed: 19945768
DOI: 10.1016/j.ejcb.2009.10.008 -
Human Genetics 1980Neuraminidase activity in cultured fibroblasts from patients either with various forms of sialidosis or with I-cell disease (ICD) or mucolipidosis (ML) III has been...
Neuraminidase activity in cultured fibroblasts from patients either with various forms of sialidosis or with I-cell disease (ICD) or mucolipidosis (ML) III has been determined by both a colorimetric and a fluorometric method. The former applied to frozen fibroblast pellets demonstrated a specific deficiency of neuraminidase in patients with the sialidoses. The enzyme was also deficient in I-cells, as were other lysosomal hydrolases. With the fluorogenic substrate these data could be confirmed and extended, and elementary kinetics of neuraminidase studied. In unfrozen freshly harvested fibroblasts, neuraminidase activity was severalfold that in frozen aliquots. A comparative and simultaneous study could not reveal substantial differences between the residual neuraminidase activity found in the various clinical forms of sialidosis. And, in fibroblasts from patients with ICD, also called ML II, the deficiency of this enzyme is quantitatively similar to that in the sialidoses, but the residual activity in ML III is three times higher. In both ML II and ML III the defect is probably secondary to the unknown metabolic error.
Topics: Cells, Cultured; Colorimetry; Fibroblasts; Fluorometry; Humans; Mucolipidoses; Neuraminidase
PubMed: 7372342
DOI: 10.1007/BF00287060 -
American Journal of Medical Genetics.... Sep 2003
Topics: Acetylglucosamine; Humans; Mucolipidoses; Phosphotransferases
PubMed: 12949982
DOI: 10.1002/ajmg.a.20290 -
Tanpakushitsu Kakusan Koso. Protein,... Apr 1988
Topics: Humans; Mucolipidoses
PubMed: 3270883
DOI: No ID Found -
Postgraduate Medical Journal Aug 1977The various disorders caused by heritable defects in complex carbohydrate catabolism comprise two groups: (A) The mucopolysaccharidoses, six main and several subtypes... (Review)
Review
The various disorders caused by heritable defects in complex carbohydrate catabolism comprise two groups: (A) The mucopolysaccharidoses, six main and several subtypes are described. (B) The mucolipidoses (oligosaccharidoses), at least nine types being recognized. Whilst most of these are now well defined by clinical and biochemical studies, much of the sequence of events from the intrinsic metabolic error to their clinical features remains obscure. Most are transmitted as autosomal recessive conditions, a mode of inheritance often, as with these disorders, associated with enzymic deficiencies. All patients display the Hurler phenotype, but this, as also the characteristic bone changes, varies widely in severity both within and between the specified types of disease. The radiological abnormalities--dysostosis multiplex--indicate the broad disease complex and are rarely type-specific; diagnostic precision needing knowledge of both clinical and biochemical examinations. In several types mental development is normal and bone changes are mild, so permitting confusion with other forms of bone dysplasia or disease.
Topics: Bone Diseases, Developmental; Diagnosis, Differential; Humans; Mucolipidoses; Mucopolysaccharidoses; Radiography
PubMed: 411121
DOI: 10.1136/pgmj.53.622.441 -
Journal of Biological Regulators and... 2020Mucolipidosis II and III are lysosomal storage diseases caused by pathogenetic mutations in GNPTAB and GNPTG genes which cause an impaired activity of the lysosomal...
Mucolipidosis II and III are lysosomal storage diseases caused by pathogenetic mutations in GNPTAB and GNPTG genes which cause an impaired activity of the lysosomal hydrolase N-acetylglucosamine- 1-phosphotransferase, a key enzyme in the synthesis of the mannose-6-phosphate targeting signals on lysosomal enzymes. Patients with MLII alpha/beta present coarse facial features, cessation of statural growth, important skeletal manifestations, impaired neuromotor development and cardiorespiratory involvement. All children appear to have cardiac involvement, but severe dilated cardiomyopathy is uncommon. In this report we describe the case of an 11-month-old girl who is affected by a MLII. Analysis of the GNPTAB gene identified at a heterozygous level the previously described gene variants c. 2693delA p(Lys898Serfs*13) and c. 2956C>T p(Arg986Cys). Her main clinical features were coarse face with gingival hypertrophy, dysostosis multiplex, recurrent respiratory infection and an early onset of dilated cardiomyopathy, an uncommon feature for MLII. To our knowledge, dilated cardiomyopathy has been previously described in literature in only two cases of MLII and in one patient affected by MLIII.
Topics: Cardiomyopathy, Dilated; Child; Female; Humans; Infant; Mucolipidoses; Mutation; Transferases (Other Substituted Phosphate Groups)
PubMed: 33000604
DOI: No ID Found