Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two brothers with oligosymptomatic mucopolysaccharidosis VII were observed from age 11 8/12 to 16 years, and 15 1/2 to 19 years, respectively. Asymptomatic thoracic kyphosis and mild scoliosis were the prominent clinical features. Herniae, hepatosplenomegaly, corneal clouding and shortness of stature were absent. Both had Alder type granulations in polymorphonuclear leukocytes and to a lesser degree in monocytes. Ultrastructural analysis of blood leukocytes revealed polymorphous inclusions of probably more than one class of organic substances. Radiological signs were mild, confined to the spine and consisted of irregularities of upper and lower vertebral plates, of vertebral flattening and some osteophytic changes. Both patients excreted excessive amounts of acid mucopolysaccharides in urine and also globoside. Cultured skin fibroblasts of both patients contained metachromatic granules, had only approx. 10% of normal beta-glucuronidase activity and degraded sulfated mucopolysaccharides at a slower than normal rate. Sera of the patients had none or minimal beta-glucuronidase activity, the mother's serum had subnormal and the father's serum low-normal activity. The older brother is the oldest known case of mucopolysaccharidosis VII. As this hereditary disorder may take a remarkably mild clinical course, beta-glucuronidase-deficient juveniles may exist undetected in the general population.
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PMID:Unusually mild course of beta-glucuronidase deficiency in two brothers (mucopolysaccharidosis VII). 10 85

The mucopolysaccharidosis represent a broad spectrum of disorders due to the deficiency of one of a group of enzymes which degrade three classes of mucopolysaccharides: heparan sulfate, dermatan-sulfate and keratan sulfate. The general phenotype includes coarse facies, corneal clouding, hepatosplenomegaly, joint stiffness, hernias, dysostosis multiplex, mucopolysaccharides excretion in the urine and metachromatic staining in peripheral leukocytes and bone marrow. Various components of the MPS phenotype are also found in the mucolipidoses, glycoprotein storage diseases. Detailed clinical and radiologic evaluation and identification of the type of MPS excreted in the urine help to narrow the diagnosis possibilities. Definitive diagnosis requires assay of specific enzymes in various tissues such as cultured skin fibroblasts. For the moment there are 14 types of known mucopolysaccharidoses, including several subtypes. They are classified into Hurler's syndrome (MPS I-H); Scheie's syndrome (MPS I-S); Hurler-Scheie's syndrome (MPS I-H/S); Hunter's syndrome A, B (MPS II-A, B); Sanfilippo's syndrome A,B,C,D (MPS II-A,B,C,D); Morquio's syndrome A,B,C (MSP IV-A,B,C); Maroteaux-Lamy's syndrome (MPS VI) and Sly's syndrome MPS VII). The mucopolysaccharidosis incidence is around 0.04-0.3% of the newborn and they are 1.5% of all congenital disorders. All mucopolysaccharidosis are autosomal recessive disorders, except for Hunter's syndrome that is X-linked and recessive. Patient suffering of MPS, usually, don't show clinical sign from their birth in fact they develop later their characteristics. The average surviving of this patients is around 20-30 years old, and the exitus is due to cardiac failure or to infections to the gastrointestinal tract or to instability of atlantoaxial joint.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mucopolysaccharidosis. A case report of Morquio's type-A disease (MPS IV-A)]. 129 76

We report on a 20-year-old male with a beta-glucuronidase (GUSB) deficiency mucopolysaccharidosis. He had pectus carinatum, gross thoracic kyphoscoliosis, and hip dysplasia, a picture which became conspicuous after age 4 years. Hepatosplenomegaly, herniae, corneal clouding, and neurological abnormalities were absent. Although he had Alder-type granulations in his polymorphonuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. Electron microscopic examination of skin and gingival biopsies, leukocytes, and cultured skin fibroblasts showed numerous single membrane-limited vacuoles either empty or filled with fibrillogranular material; this last tissue did not contain metachromatic granules. Radiographs demonstrated a distinct spondyloepiphyseal dysplasia in which the most striking changes were confined to the thoracic spine (flattening and collapse in T7, T8 and T10 vertebral bodies) and to the femoral capital epiphyses (irregularities and fragmentation). The activity of GUSB in the patient's serum, leukocytes, and fibroblasts was severely decreased; the GUSB activity in the serum and leukocytes from the parents and 2 asymptomatic sibs was subnormal. Immunoblot analysis showed very low levels of cross-reactive material towards anti-GUSB antiserum in the patient's leukocyte and fibroblast extracts. This patient was more severely affected in his skeleton than other described patients with an oligosymptomatic chronic form. This case broadens the clinical and biochemical picture associated with GUSB deficiency and may represent a new variant of the disease.
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PMID:Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a chronic variant with an oligosymptomatic severe skeletal dysplasia. 145 83

We studied two cases of beta-glucuronidase deficiency. One patient's disease was present at birth and the other patient's disease appeared in early childhood. The symptoms observed in both patients, although of differing severity, included peculiar facies, cloudy cornea, hepatosplenomegaly, hernia, kyphosis, recurrent infections, short stature, and developmental delay, as well as increased excretion of urinary chondroitin sulfate A/C and decreased levels of beta-glucuronidase activity. We reviewed all of the reported cases and examined the biochemical and clinical heterogeneity observed in this disorder.
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PMID:Beta-glucuronidase deficiency. A heterogeneous mucopolysaccharidosis. 315 9

The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases resulting from the partial catabolism of several glycosaminoglycans (GAGs). Depending on the particular enzyme deficient in activity, the MPS syndromes are defined into groups MPS I through VII, with several subgroups for a total of 10 disorders. In humans, clinical features include dysostosis multiplex, hepatosplenomegaly, hypertelorism, macroglossia, hypoplastic and irregularly shaped teeth, hyperplastic lips and gingiva, facial dysmorphia, corneal clouding, and mental retardation. MPS I (alpha-L-iduronidase deficiency) and VI (arylsulfatase B deficiency) have been described in cats, MPS VII (beta-glucuronidase deficiency) in dogs. Biochemically, these syndromes appear the same as their human counterparts and have similar clinical characteristics. All are inherited as autosomal recessive traits. The purpose of this study was to analyze the craniofacial aspects of these diseases in the animal models and compare these data with descriptions of the human syndromes. A total of 28 live animals were examined. Thirty-one skulls prepared from postmortem specimens were measured directly and radiographed. Controls were closely related family members of the same sex and similar age without the disease, clinically or biochemically. The data indicated that, as in the human syndromes, each is distinct, and the skull bones most severely affected are those of endochondral origin.
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PMID:Craniofacial abnormalities in animal models of mucopolysaccharidoses I, VI, and VII. 800 22

The mucopolysaccharidoses are a group of lysosomal storage diseases caused by deficiency of an enzyme required for the normal degradation of glycosaminoglycans. Patients with mucopolysaccharidosis typically have widespread lysosomal storage, skeletal and central nervous system disease, and hepatosplenomegaly. Some patients with mucopolysaccharidosis may benefit from enzyme replacement therapy or bone marrow transplantation. Animal models of mucopolysaccharidosis have proven valuable for the evaluation of the effectiveness of potential treatments for patients with lysosomal storage disease. A murine model of MPS VII (Sly syndrome) has proven particularly useful because of its well-defined genetics and its well-characterized clinical, pathologic, and biochemical alterations, which resemble those seen in patients with mucopolysaccharidosis. Correction of these alterations forms the basis for evaluation of the effectiveness of novel treatments. A wide range of therapies have been tested using this model, including enzyme replacement therapy, bone marrow, stem cell, and neural progenitor cell transplantation, and a variety of viral-mediated gene therapies. The inferences drawn from these therapeutic studies using the murine MPS VII model are likely generalizable to other lysosomal storage diseases.
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PMID:Murine mucopolysaccharidosis VIL: impact of therapies on the phenotype, clinical course, and pathology in a model of a lysosomal storage disease. 1177 44

Mucopolysaccharidosis type VII or Sly syndrome is an autosomal recessive disorder of glycosaminoglycan storage leading to variable clinical symptoms, such as hepatosplenomegaly, bone deformities, hearing loss, corneal opacities, mental retardation, and hydrops fetalis in affected individuals. The disease is caused by approximately 40 different mutations in the beta-glucuronidase gene. Detection of the most common mutation L176F by single-strand conformation polymorphism (SSCP) was not always successful. Although DNA sequencing followed by PCR amplification can easily detect this mutation, accessibility to a DNA sequencer or useful reagents in the sequencing procedure is not readily available in many countries. A PCR-based restriction fragment length polymorphism (RFLP) developed in this report would allow rapid and easier detection of this mutation for screening new patients or neonates of heterozygous parents. Analysis of intragenic polymorphic sites in the L176F patients identified two distinct alleles; the predominant one probably originated in Spain.
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PMID:PCR-based restriction fragment length polymorphism and haplotype of the most common mutation L176F in the beta-glucuronidase gene. 1739 95

A 6 month-old infant presenting with severe mitral regurgitation was found to have hepatosplenomegaly, corneal clouding, and Alder-Reilly granules in the leucocytes. Extremely low levels of beta glucuronidase confirmed the diagnosis of Sly disease (Mucopolysaccharidosis VII). This is the first case of MPS VII reported from India.
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PMID:Sly Disease: Mucopolysaccharidosis Type VII. 1894 60

Mucopolysaccharidosis VII (MPS VII; Sly syndrome) is an autosomal recessive disorder caused by a deficiency of beta-glucuronidase (GUS, EC 3.2.1.31; GUSB). GUS is required to degrade glycosaminoglycans (GAGs), including heparan sulfate (HS), dermatan sulfate (DS), and chondroitin-4,6-sulfate (CS). Accumulation of undegraded GAGs in lysosomes of affected tissues leads to mental retardation, short stature, hepatosplenomegaly, bone dysplasia, and hydrops fetalis. We summarize information on the 49 unique, disease-causing mutations determined so far in the GUS gene, including nine novel mutations (eight missense and one splice-site). This heterogeneity in GUS gene mutations contributes to the extensive clinical variability among patients with MPS VII. One pseudodeficiency allele, one polymorphism causing an amino acid change, and one silent variant in the coding region are also described. Among the 103 analyzed mutant alleles, missense mutations accounted for 78.6%; nonsense mutations, 12.6%; deletions, 5.8%; and splice-site mutations, 2.9%. Transitional mutations at CpG dinucleotides made up 40.8% of all the described mutations. The five most frequent mutations (accounting for 44/103 alleles) were exonic point mutations, p.L176F, p.R357X, p.P408S, p.P415L, and p.A619 V. Genotype/phenotype correlation was attempted by correlating the effects of certain missense mutations or enzyme activity and stability within phenotypes. These were in turn correlated with the location of the mutation in the tertiary structure of GUS. A total of seven murine, one feline, and one canine model of MPS VII have been characterized for phenotype and genotype.
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PMID:Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome). 1922 84

Chitotriosidase (ChT) is an enzyme that is selectively activated in tissue macrophage. This property of ChT makes it a potential marker for many disease process and prognostication. Present study has been carried out to know the significance of ChT as a screening marker in lysosomal storage disorders (LSDs) where tissue macrophage activation is commonly observed due to accumulation of substrate in various organs of the body. Study comprises of 20 healthy children in the age range of 10 days to 5 yrs and 56 children in the age range of 2.5 months to 13 yrs with regression of milestones, skeletal dysplasia, neuroregression and hepatosplenomegaly were selected for plasma ChT who had confirmed LSDs as carried out by specific lysosomal enzyme study from the leukocytes or fibroblasts. Plasma ChT was 55.21 +/- 20.81 nmol/ml/hr in twenty healthy age matched controls. Plasma ChT level was 42.88 to 79.78 nmol/ml/hr in thirteen of 56 (23.21%) children with LSDs like Morquio-B, Pompe, Metachromatic leucodystrophy (MLD), Sandhoff and Niemann-Pick disease type C (NPD-C). While in 43 (76.78%) children it was in the range of 213.74 to 23,511.40 nmol/ml/hr. who had LSDs like Morquio-B, Sly syndrome, MLD, GM2 Gangliosidosis, NPD-A/B and Gaucher disease (GD). Marked elevated ChT (4,000 to 23,511 nmol/ml/hr) was observed in all cases of GD (n=7) and NDP-A/B. It can be concluded from the present study that moderately raised activity of ChT can be utilized as a positive predictive test for certain LSD's. Those with marked elevated ChT have confirmed GD or NPD-A/B making it a strong screening marker for this group of diseases.
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PMID:Plasma chitotriosidase activity in children with lysosomal storage disorders. 1993 66


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