1/17. In-utero diagnosis of mucopolysaccharidosis type VII in a fetus with an enlarged nuchal translucency.Mucopolysaccharidosis type VII was diagnosed prenatally during the first pregnancy of a Turkish consanguineous couple, following diagnostic work-up of an increased nuchal translucency detected by ultrasound at 13 weeks of gestation. Mucopolysaccharidosis type VII (MPS VII) or Sly syndrome is a rare autosomal recessive lysosomal storage disease, caused by the deficiency of the enzyme beta-glucuronidase. The most severe form of MPS VII manifests itself by non-immune fetal hydrops. Tests for the diagnosis of metabolic disorders, especially lysosomal diseases, are essential when the major causes of hydrops fetalis have been excluded. The presence of a beta-glucosidase deficiency, Gaucher's disease, in the infant of the patient's sister emphasizes the importance of a complete family history in consanguineous couples and the risk for several recessive diseases in some families.- - - - - - - - - - ranking = 1keywords = mucopolysaccharidosis (Clic here for more details about this article) |
2/17. Mutational analysis in longest known survivor of mucopolysaccharidosis type VII.mucopolysaccharidosis vii (MPS VII) is an autosomal recessive disorder caused by the deficiency of beta-glucuronidase leading to the intralysosomal storage of heparan, dermatan, and chondroitin sulfate. Here, we report the identification of two novel missense mutations K350N and R577L in a 37-year-old patient with beta-glucuronidase deficiency and a relatively mild MPS VII phenotype. Expression of the K350N mutation in baby hamster kidney cells has revealed residual enzymatic activity and normal transport of the enzyme to the lysosome. However, expression of the R577L or the double mutant K350N/R577L results in rapid degradation of the enzyme in early biosynthetic compartments and a total loss of enzymatic activity. We attribute the mild phenotype to the residual catalytic activity provided by the K350N mutant. At the time of her death at the age of 37 years, this patient was the longest known survivor with MPS VII.- - - - - - - - - - ranking = 1keywords = mucopolysaccharidosis (Clic here for more details about this article) |
3/17. Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a chronic variant with an oligosymptomatic severe skeletal dysplasia.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.- - - - - - - - - - ranking = 0.25keywords = mucopolysaccharidosis (Clic here for more details about this article) |
4/17. Craniovertebral instability with spinal cord compression in a 17-month-old boy with Sly syndrome (mucopolysaccharidosis type VII): a surgical dilemma.STUDY DESIGN: A case study with review of surgical technique in craniovertebral stabilization for young children with mucopolysaccharidosis. OBJECTIVES: To describe an interesting patient with a rare metabolic disorder and review surgical technique for craniovertebral instability in this rare patient population. SUMMARY OF BACKGROUND DATA: Craniovertebral instability has been reported in patients with mucopolysaccharidosis and poses a problem for spinal surgery because of the inherent metabolic disorder and age at presentation. We present the first case of craniovertebral instability and spinal cord compression occurring in Sly syndrome (mucopolysaccharidosis type VII) who is the youngest patient afflicted with this metabolic disorder to undergo craniovertebral stabilization. methods: A 17-month-old boy presented with inability to support his head, decreasing muscle strength in all extremities, distended abdomen, and shortness of breath. The patient was found to have a dilated cardiomyopathy, hepatosplenomegaly, abnormal hepatobiliary function, corneal clouding, and a questionable tracheal anomaly. genetic testing provided a diagnosis of Sly syndrome, mucopolysaccharidosis type VII. magnetic resonance imaging revealed focal stenosis with significant spinal cord compression at the craniovertebral junction. neurologic examination revealed normal muscle volume with strength 3/5 in all extremities and significant weakness in the neck muscles with instability at the craniovertebral junction. RESULTS: On a concerted preoperative medical clearance by pediatric intensive care, pediatric neuroanesthesia, pediatric cardiology, pediatric gastroenterology, and pediatric neurosurgery, the patient underwent occipital to C3 decompression and fusion with autogenous rib grafts. The patient was placed in a prefitted halo-vest after surgery and was neurologically intact. CONCLUSIONS: This case demonstrates the heterogeneity of cervical spine deformities among the mucopolysaccharidosis syndromes and confirms the propensity for deposition of glycosaminoglycans at the craniovertebral junction. Further studies should investigate the etiology for this propensity of glycosaminoglycan deposition at the craniovertebral junction. We think that this case demonstrates that, with appropriate preoperative planning, these patients can undergo successful posterior cervical arthrodesis despite their age or metabolic defects.- - - - - - - - - - ranking = 2.25keywords = mucopolysaccharidosis (Clic here for more details about this article) |
5/17. Collection of a mobilized peripheral blood apheresis product from a patient with mucopolysaccharidosis type VII and subsequent CD34 cell isolation.The effectiveness of bone marrow transplantation for lysosomal storage diseases like mucopolysaccharidosis type VII (MPSVII) suggests that a gene therapy strategy targeting autologous hematopoietic progenitor cells could be successful. Given the severe systemic manifestations of MPSVII including storage disease in the bone and bone marrow, it was unclear whether sufficient numbers of hematopoietic progenitor cells (CD34 ) could be mobilized into the peripheral circulation and subsequently purified from these patients. As reported here, G-CSF mobilization and apheresis were successful, providing a product of 4 x 10(10) nucleated cells containing 0.3% CD34 progenitors. CD34 cells were magnetically separated from the product to a final purity of 85% with a 64% yield. These results indicate that hematopoietic progenitors can safely be gathered from an MPSVII patient in numbers sufficient for the trial of clinical gene therapy applications.- - - - - - - - - - ranking = 1.25keywords = mucopolysaccharidosis (Clic here for more details about this article) |
6/17. Coarctation of the thoraco-abdominal aorta associated with mucopolysaccharidosis VII in a child.Herein we describe a case of atypical coarctation of the thoraco-abdominal aorta associated with mucopolysaccharidosis vii in a 4-year-old girl. aortography showed diffuse narrowing of the descending aorta. An extra-anatomic bypass was constructed using an 8-mm Dacron graft (Meadox Medicals Inc, Oakland, NJ) between the proximal and distal portion of the descending aorta. Balloon angioplasty was necessary to treat stenoses in the infrarenal abdominal aorta. Two years postoperatively at age 6, aortography revealed no stenosis at the anastomotic sites or in the prosthesis, but the hypoplastic segment of the descending aorta between the anstomoses was completely occluded.- - - - - - - - - - ranking = 1.25keywords = mucopolysaccharidosis (Clic here for more details about this article) |
7/17. Recurrent fetal hydrops due to mucopolysaccharidoses type VII.hydrops fetalis is associated with a wide range of abnormalities. In about 20% of cases of non-immune fetal hydrops, no cause is found despite investigations including routine post-mortem examination and enzyme studies may be indicated to detect an underlying metabolic storage disease. Fetal hydrops due to mucopolysaccharidosis type VII is very rare and a prenatal diagnosis is not usually made. We report a case of mucopolysaccharidosis type VII presenting as recurrent fetal hydrops and review the clinico-pathological features of this disorder.- - - - - - - - - - ranking = 0.5keywords = mucopolysaccharidosis (Clic here for more details about this article) |
8/17. Low beta-glucuronidase activity in a healthy member of a family with mucopolysaccharidosis vii.A phenotypically normal mother of a mucopolysaccharidosis vii child, is reported with an unusually low beta-glucuronidase activity. Low enzyme activity was systemic (6-10% of controls) and residual beta-glucuronidase in leukocytes had an apparently normal Km value. [35S]sulphate incorporation and chase assays in fibroblasts gave values similar to control cells. A normal excretion pattern of glycosaminoglycan was found in this woman's urine. Low enzymatic activity can be related to a non-pathological 'pseudodeficiency' allele for beta-glucuronidase; this woman appears to be an apparent compound heterozygote for this allele and mucopolysaccharidosis vii. Her next pregnancy was monitored by chorionic villus sampling and a heterozygous fetus was suspected. These studies stress the need for complete enzyme investigations of obligate carriers for mucopolysaccharidoses in order to prevent difficulties at prenatal analysis.- - - - - - - - - - ranking = 1.5keywords = mucopolysaccharidosis (Clic here for more details about this article) |
9/17. Mutational studies in a patient with the hydrops fetalis form of mucopolysaccharidosis type VII.Four prior mutations have been reported in three patients with beta-glucuronidase deficiency mucopolysaccharidosis (MPS VII), none of whom had the severe, infantile, hydropic form of the disease. We identified two mutations in the first reported case of nonimmune hydropic MPS VII whose cultured fibroblasts had < 1% of residual activity. The first mutation was a C-->T transition at position 1061 of the cDNA in exon 6 that gave rise to an Ala-->Val substitution in codon 354 (A354V). The second was a C-->T transition at position 1831 in exon 12 that produced an Arg-->Trp substitution in codon 611 (R611W). Transient expression in COS-7 cells revealed that both mutant enzymes were synthesized as normal-size precursors in normal quantities, but both exhibited accelerated turnover. The expressed A354V enzyme had a t0.5 (half-life) of 33 hr (wild-type t0.5 > 60 hr) and a specific activity 35% of wild-type enzyme. The R611W enzyme had a t0.5 of 20 hr and no detectable catalytic activity. The t0.5 of enzyme produced on cotransfection with A354V and R611W was nearly identical to that of A354V alone. Mutant enzyme expressed in transfected murine MPS VII cells gave similar residual activities relative to the wild-type enzyme. In cos cells, the A354V monomers formed mixed tetramers with coexpressed rat monomers, but the product of R611W did not. The higher than expected activity, both in cos cells and in murine MPS VII cells expressing A354V, provides further evidence that overexpression can partially correct some beta-glucuronidase mutations, apparently by driving the folding reaction of monomers or the assembly into tetramers by mass action.- - - - - - - - - - ranking = 1.25keywords = mucopolysaccharidosis (Clic here for more details about this article) |
10/17. mucopolysaccharidosis vii: postmortem biochemical and pathological findings in a young adult with beta-glucuronidase deficiency.The postmortem biochemical and pathological findings in the first patient reported with mucopolysaccharidosis vii are described. Clinical, radiographic, and biochemical features of this 19-yr-old black man were initially reported in 1973 when, at age 2 1/2 yr his enzymatic defect, deficiency of beta-glucuronidase, was identified. The autopsy findings are now described with biochemical data further characterizing the enzyme deficiency and resultant glycosaminoglycan accumulation. He had dysostosis multiplex and extensive cardiovascular lesions including arterial stenosis, and marked fibrous thickening of the atrioventricular and aortic valves. Microscopic evidence of lysosomal storage was found in bone, cartilage, arteries and cardiac valves, liver, spleen, lymph nodes, eyes, adrenal, pituitary, and the central nervous system. In the brain, storage was localized to specific regions, primarily intraneuronal, and appeared ultrastructurally as delicate whorled filamentous accumulations in lysosomes. Similar filamentous storage also occurred in medial cells of the aorta. Multiple postmortem tissues contained only trace amounts of beta-glucuronidase and elevated glycosaminoglycans, predominantly chondroitin 4- and 6-sulfate.- - - - - - - - - - ranking = 0.25keywords = mucopolysaccharidosis (Clic here for more details about this article) |
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