Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysosomal storage disorders (LSD) are chronic progressive diseases that have a devastating impact on the patient and family. Most patients are clinically normal at birth but develop symptoms early in childhood. Despite no curative treatment, a number of therapeutic options are available to improve quality of life. To achieve this, there is a pressing need for newborn screening to identify affected individuals early, before the onset of severe irreversible pathology. We have developed a multiplexed immune-quantification assay of 11 different lysosomal proteins for the identification of individuals with an LSD and evaluated this assay in a retrospective study using blood-spots from; newborns subsequently diagnosed with an LSD (n=19, six different LSD), individuals sampled after diagnosis of an LSD (n=92, 11 different LSD), newborn controls (n=433), and adult controls (n=200). All patients with mucopolysaccharidosis type I (MPS I), MPS II, MPS IIIA, MPS VI, metachromatic leukodystrophy, Niemann-Pick disease type A/B, and multiple sulfatase deficiency could be identified by reduced enzyme levels compared to controls. All mucolipidosis type II/III patients were identified by the elevation of several lysosomal enzymes, above the control range. Most Fabry, Pompe, and Gaucher disease patients were identified from either single protein differences or profiles of multiple protein markers. Newborn screening for multiple LSD is achievable using multiplexed immune-quantification of a panel of lysosomal proteins. With further validation, this method could be readily incorporated into existing screening laboratories and will have a substantial impact on patient management and counseling of families.
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PMID:Newborn screening for lysosomal storage disorders. 1660 Jun 51

Lysosomal storage diseases (LSD) are inborn errors of metabolism secondary to lysosomal enzyme defects and are characterized by a progressive accumulation of nondigested macromolecules provoking cellular dysfunction and clinical manifestations. The diagnosis of these diseases can be confirmed easily in most cases by immuno-enzymatic techniques and molecular biology. Even though these enzymatic deficits result in an accumulation of pathological substrates, the underlying mechanisms responsible for the pathogenesis of the disease are not entirely known. Nevertheless, the distribution of the accumulated material determines the affected organs. More particularly in the central nervous system (CNS), neurons are often involved due to the accumulation of storage material and their incapacity of renewal. LSD can be responsible for mental retardation or for a neurodegenerative course in the central nervous system. The peripheral nervous system and the muscle can also be severely impaired. Hematopoietic stem cell transplantation was the first therapy, demonstrating efficacy especially on the neurological involvement of various LSD. Enzyme replacement therapy is now available for Gaucher disease, Fabry disease, mucopolysaccharidoses type I, type II, and type VI, and Pompe disease. Inhibition of the synthesis of the accumulated substrate by small molecules which also have the capacity to diffuse through the blood-brain barrier is another treatment option. New therapeutic strategies using the properties of molecular chaperones and of read-through molecules for nonsense mutations have been studied in vitro and hopefully will soon find clinical applications while intrathecal enzymes are currently studies in clinical trials for MPSII, MPS IIIA and MLD.
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PMID:Enzyme replacement therapy and substrate reduction therapy in lysosomal storage disorders with neurological expression. 2362 8