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At least 19 recordsLinked to original sources
PubMed1996

[Mucopolysaccharidoses from the view point of mucopolysaccharidoses families--10 years' experiences of the "Austrian Society for Mucopolysaccharidoses"].

The mucopolysaccharidoses (MPS) are rare inborn errors of metabolism. They are caused by defects in enzymes which are necessary for the degradation of mucopolysaccharides. An effective causal treatment is not available as yet. Nevertheless, it is the duty of the doctor, both from the medical and human aspect to assist MPS patients and their families physically and psychologically over many years. This task needs much empathy, working morale and knowledge of these diseases on the part of the medical adviser involved, but also demonstrates the limitations of active medical treatment. Since 10 years the "Austrian Society for Mucopolysaccharidoses" has tried to fill the gap between the MPS families' need for help and the still discouraging current medical treatment prospectives.

Adaptation, Psychological↗
PubMedDate not supplied

Mucopolysaccharidoses and the eye.

The mucopolysaccharidoses (MPSs) are a group of disorders caused by inherited defects in lysosomal enzymes resulting in widespread intra- and extra-cellular accumulation of glycosaminoglycans. They have been subdivided according to enzyme defect and systemic manifestations and include MPS IH (Hurler), MPS IS (Scheie), MPS IH/S (Hurler/Sheie), MPS II (Hunter), MPS III (Sanfilippo), MPS IV (Morquio), MPS VI (Maroteaux-Lamy), MPS VII (Sly) and MPS IX (Natowicz). The mucopolysaccharidoses have a spectrum of systemic manifestations, including airway and respiratory compromise, skeletal deformities, intellectual and neurological impairment, cardiac abnormalities, and gastrointestinal problems. Ocular manifestations are common in the mucopolysaccharidoses and may result in significant visual impairment. Corneal opacification of varying severity is frequently seen, as well as retinopathy, optic nerve swelling and atrophy, ocular hypertension, and glaucoma. New treatment modalities for the systemic manifestations of the mucopolysaccharidoses include bone marrow transplant and enzyme replacement therapy, and have resulted in an improved prognosis in many cases. This article reviews the systemic and ocular manifestations of the mucopolysaccharidoses, as well as new treatment options, and discusses the ophthalmic management of mucopolysaccharidosis patients.

Eye Diseases↗
PubMed1976

The mucopolysaccharidoses: inborn errors of glycosaminoglycan catabolism.

The mucopolysaccharidoses are genetic disorders of glycosaminoglycan metabolism. Patients with these diseases accumulate within the lysosomes of most tissues excessive amounts of dermatan and/or heparan sulfates, or of keratan sulfate. The clinical consequences of such glycosaminoglycan storage range from skeletal abnormalities to cardiovascular problems, and to motor and mental retardation. In all mucopolysaccharidoses, except Morquio disease, an excessive accumulation of sulfate-labeled glycosaminoglycans has been demonstrated in fibroblasts cultured from the patient's skin. It was subsequently shown that this was due to the deficiency of specific proteins which were named "corrective factors", because their addition to the culture medium effected a normalization of the impaired glycosaminoglycan catabolism in the respective mucopolysaccharidosis fibroblasts. The investigation of the function of the corrective factors, and other studies, led to the identification of the enzymatic defect in each of the mucopolysaccharidoses. Seven lysosomal enzyme deficiencies are now recognized among this group of disorders. A classification of the diseases, according to the mutant gene products, reveals that there is considerable phenotypic variation not only between diseases, but also within several disease types. With the availability of the appropriate enzyme assays, the previous difficulties in diagnosing these disorders have now been overcome. Methods are also available for the prenatal diagnosis, and the detection of heterozygous individuals, in most of the mucopolysaccharidoses. Although correction of the metabolic defect through enzyme replacement has been achieved in tissue culture, many problems remain to be solved before such therapy may become applicable in the patients themselves.

Glycosaminoglycans↗
PubMed1992

Attempted enzyme replacement using human amnion membrane implantations in mucopolysaccharidoses.

Amnion membrane implantation has been proposed as an approach to enzyme replacement in mucopolysaccharidoses. Human amnion membranes have been subcutaneously implanted in the abdominal wall in 19 patients with mucopolysaccharidoses (MPS I, II and III). A protocol was developed for the objective evaluation of experimental treatments of these patients. Systematic evaluation of the clinical status before and 6 months after amnion membrane implantation reveals no change in function except improvement in joint mobility. The sum of all joint movements showed improvement from baseline values to 6 months after implantation by ANOVA followed by post-hoc analysis (p less than 0.056). The only specific joint movements to significantly improve after 6 months were shoulder extension (p less than 0.01) and hip internal rotation (p less than 0.05). Serial measurements of the deficient lysosomal enzyme activity in serum and white blood cells did not increase in any patient after amnion membrane implantation. Urinary glycosaminoglycan excretion decreased transiently in 2 of 10 patients after implantation, but a second amnion membrane implantation did not result in any change. Biopsy of the implantation site in 10 patients 6 months after amnion membrane implantation revealed a foreign-body reaction with giant cell formation and fibrosis and no recognizable amnion membrane tissue. We conclude that human amnion membrane implantation is not an effective therapy in mucopolysaccharidoses.

Abdominal Muscles↗
PubMed2005

Cumulative incidence rates of the mucopolysaccharidoses in Germany.

In order to estimate the cumulative incidence rates of the mucopolysaccharidoses (MPS) in Germany, a retrospective epidemiological survey covering the period between 1980 and 1995 was implemented. Multiple ascertainment sources were used to identify affected patients. A prevalence of approximately 0.69 cases per 100,000 births was obtained for MPS I (Hurler phenotype). Within the study period, 4 patients with Hurler/Scheie phenotype and 7 cases with Scheie disease were detected. The cumulative incidence for MPS II (Hunter syndrome) was estimated as 0.64 cases per 100,000 births (1.3 cases per 100,000 male live births); that for MPS III (Sanfilippo syndrome types A, B and C) as 1.57 cases in 100,000 births; that for MPS IV A (Morquio syndrome) as 0.38 cases in 100,000; and that for MPS VI (Maroteaux-Lamy syndrome) as 0.23 cases per 100,000 births. Two cases of MPS IVB (beta-galactosidase deficiency) have been identified, but no patients with MPS VII or MPS IX. A relatively high number of patients with MPS IIIB, MPS IVA and MPS VI were of Turkish origin. The crude rate for all types of mucopolysaccharidoses is approximately 3.53 cases in 100,000 live births. The cumulative incidence pattern of MPS in Germany was compared with the corresponding rates among other industrial nations obtained from recent literature: the crude cumulative rates for all types of mucopolysaccharidoses (3.4-4.5 in 100,000 live births) were similar among all published populations; however, different frequencies of the various forms of MPS were observed.

Female↗
PubMed1986

Hepatic fibrosis in the mucopolysaccharidoses.

The mucopolysaccharidoses are a group of clinically progressive, heritable, lysosomal storage disorders. Many organ systems are affected due to widespread accumulation of incompletely degraded mucopolysaccharide. The novel finding of hepatic fibrosis in each of six cases of mucopolysaccharidosis examined at autopsy (including examples of Hurler syndrome, Hunter syndrome, and Sanfilippo syndrome) is described. In each instance, the liver was diffusely involved by fibrosis that outlined the lobules, and there was extensive hepatocyte and Kupffer cell vacuolization. The pattern of hepatic fibrosis is not explained by either cardiac failure or drug toxicity. It is hypothesized that the hepatic fibrosis is due to the abnormal accumulation of a hepatotoxic metabolite. The frequency and severity of liver disease in the mucopolysaccharidoses deserve further study. In particular, with the advent of bone marrow transplantation as therapy for some of the mucopolysaccharidoses, the question of whether cirrhosis develops in these patients and, if so, what its rate of progression is, should be addressed.

Adolescent↗
PubMed1978

An improved determination of total glycosaminoglycans in body fluids by formation of complexes with quinacrine: changes in amniotic fluid total glycosaminoglycans during normal pregnancies and in pregnancies at risk for mucopolysaccharidoses.

Acidic glycosaminoglycans form insoluble complexes with quinacrine and this has been exploited for their analysis in blood, urine and amniotic fluid. The method is specific for glycosaminoglycans including keratan sulphate and the samples do not have to be deproteinized. Values for normal urine, serum and amniotic fluid are presented. Urinary total glycosaminoglycans excreted by patients with mucopolysaccharidoses were also determined. The normal changes in amniotic fluid total glycosaminoglycans have been measured between 14 weeks' gestation and term, and values are given for amniotic fluid total glycosaminoglycans in several pregnancies at risk for mucopolysaccharidoses. It is suggested that this method is a potentially valuable analytical tool in the pre-natal diagnosis of mucopolysaccharidoses.

Amniotic Fluid↗
PubMed2003

Determination of monosaccharides and disaccharides in mucopolysaccharidoses patients by electrospray ionisation mass spectrometry.

The mucopolysaccharidoses are a group of lysosomal storage disorders characterised by the storage of glycosaminoglycans. With the exception of Hunters syndrome (MPS II), which is X-linked, they are autosomal recessively inherited resulting in a defect in any one of 10 lysosomal enzymes needed to catabolise glycosaminoglycans. The type and size of the glycosaminoglycans stored in lysosomes are determined by the particular enzyme deficiency. These glycosaminoglycan elevations are subsequently observed in tissue, circulation, and urine. A method has been developed for the derivatisation and quantification of sulfated N-acetylhexosamine-containing mono- and disaccharides from patient samples by electrospray ionisation tandem mass spectrometry. Urine from most mucopolysaccharidoses types had significant increases in di- and monosulfated N-acetylhexosamines (GalNAc4,6S, GalNAc6S, GalNAc4S, or GlcNAc6S) and monosulfated N-acetylhexosamine-uronic acid disaccharides (GalNAc6S-UA, GalNAc4S-UA, or GlcNAc6S-UA). Analysis of plasma and dried blood spots on filter paper collected from mucopolysaccharidoses patients showed elevations of total monosulfated N-acetylhexosamines but less than that seen in urine. Urine samples from bone marrow transplant recipients, mucopolysaccharidosis IVA and mucopolysaccharidosis VI patients, showed decreases in HexNAcS, HexNAcS(2)/GalNAc4,6S, and HexNAcS-UA post-transplant. This decrease correlated with clinical improvement to levels comparable with those identified in patients with less severe phenotypes. These metabolic markers therefore have potential applications in diagnosis, phenotype prediction and monitoring of current and future therapies, particularly for the mucopolysaccharidosis IIID, IVA, VI, and multiple sulfatase deficiency. This paper reports a sensitive and simple method for the measurement of sulfated N-acetylhexosamines and sulfated disaccharides shown to be elevated in some mucopolysaccharidosis and multiple sulfatase deficient patients.

Adolescent↗
PubMed2001

Evaluation of accumulated mucopolysaccharides in the brain of patients with mucopolysaccharidoses by (1)H-magnetic resonance spectroscopy before and after bone marrow transplantation.

In seven patients with mucopolysaccharidoses (1 Hurler, 1 Hurler-Scheie, 4 Hunter, 1 Sly), cranial (1)H-magnetic resonance spectroscopy was performed to evaluate the accumulation of mucopolysaccharides and biochemical changes in the CNS in vivo before and after bone marrow transplantation (BMT). In two of seven patients, (1)H-magnetic resonance spectroscopy was performed before and after BMT. Nuclear magnetic resonance spectra of dermatan sulfate and chondroitin sulfate-C and magnetic resonance spectroscopy of chondroitin sulfate-C and urine from patients with mucopolysaccharidoses showed resonance higher than the chemical shift of myoinositol in the brain (3.7 ppm). The resonance was considered to contain signals from mucopolysaccharide molecules. The resonance was measured as presumptive mucopolysaccharides (pMPS). In white matter lesions detected by magnetic resonance imaging, pMPS/creatine ratios and choline/creatine ratios were consistently higher than control ratios. In white matter without lesions, choline/creatine ratios were higher than control ratios. Patients with higher developmental quotient or intelligence quotient tended to show higher N:-acetylaspartate/creatine ratios and lower pMPS/creatine ratios in basal ganglia. After BMT, the pMPS/creatine ratio in white matter lesions of patient 3, with Hunter syndrome, was slightly decreased, but in none of the patients was the ratio ever below the control ratios, even 7 y after BMT. In white matter without lesions, the pMPS/creatine ratio in patient 3 was decreased to the control ratios after BMT, but although the choline/creatine ratios were gradually decreased, they remained higher than the control ratio, 2 y after BMT. These results suggest that evaluation of pMPS, choline, and N:-acetylaspartate by (1)H-magnetic resonance spectroscopy is an important technique that may provide useful biochemical information in vivo on the neurologic process and the efficacy of BMT in patients with mucopolysaccharidoses.

Adolescent↗
PubMed1992

[Mucopolysaccharidoses. Genetics, clinical pathology, therapeutic regimes].

In recent years, several clinical and biochemical studies have been published contributing to better understanding of mucopolysaccharide storage diseases. Our purpose, therefore, is, to give an updated survey of this group of lysosomal diseases for diagnostic orientation to the pathologist. The present classification of mucopolysaccharidoses is based on a mixture of clinical symptoms, demonstration of enzyme defects, analysis of urinary excretion of glycosaminoglycans (mucopolysaccharides) and historical eponyms. A broad heterogeneity has been revealed: identical enzyme defects may lead to severe mental and physical deterioration and death during childhood or to mild forms with normal adult height, intelligence, and life expectancy. Conversely, identical phenotypes may result from mutations of different genes. Various types of mucopolysaccharidoses are mostly characterized by quantitative differences of main symptoms (coarse facial features, various skeletal abnormalities, hepatosplenomegaly, corneal clouding, mental retardation, and cardiac failure). Morphologically, storage material can be observed practically in all tissues by light and/or electron microscopy. Until recently, no more than palliative treatment could be offered. In the last decade, bone marrow transplantation has become available and may have beneficial effects in selected cases. The genes of several lysosomal enzymes have been identified, and comprehensive studies to introduce the gene into defective cells are currently undertaken. However, substantial efforts are still necessary until gene transfer will become available for patients with mucopolysaccharidoses.

Brain↗
PubMed1990

[Pathomorphology of mucopolysaccharidoses].

Mucopolysaccharidoses are autosomal recessive or X-linked hereditary lysosomal storage diseases occurring to one in 10,000 to 16,000 births. The definitive diagnosis is based on the biochemical verification of the enzyme defect in cultured fibroblasts of amniotic fluid cells, in amniotic fluid, in chorionic biopsies and by determination of the urinary excretion of glycosaminoglycans. Morphological studies are of utmost importance both for genetic counselling and enlightenment of the pathogenesis. In recent years, numerous reports appeared dealing with morphological changes in different types of mucopolysaccharidoses. Based on own studies in pre- and postnatal cases, the present paper gives an update review on light and electron microscopic peculiarities of the different types and subtypes of mucopolysaccharidoses according to the classification of MCKUSICK and NEUFELD (1983). Lysosomal storage is found in practically all organs. However, there are quantitative and qualitative differences which are responsible for variations in clinical symptomatology. The purpose of this paper is to describe these differences with particular emphasis on changes in various tissues, on the pathogenetic mechanism of the storage as well as on pre- and postnatal morphological diagnostics.

Brain↗
PubMed1989

Dimethylmethylene blue-based spectrophotometry of glycosaminoglycans in untreated urine: a rapid screening procedure for mucopolysaccharidoses.

Glycosaminoglycans (GAGs) are measured in urine to screen for mucopolysaccharidoses. Other assay procedures are only qualitative (spot tests), can give false-negative results (spot tests, turbidity tests), or are relatively laborious (uronic acid-carbazole test). The present spectrophotometric procedure, based on the color reaction with dimethylmethylene blue (DMB), can be performed directly on untimed urine samples without prior precipitation. Reference values were age dependent. We tested urines of 27 patients with various mucopolysaccharidoses and compared results by three other procedures (cetylpyridinium chloride turbidity tests at pH 4.8 and at pH 7.0, and the uronic acid-carbazole test). In the DMB assay, GAGs were increased in 26 of the 27 patients. The exception was a Morquio A patient, whose activity of the defective enzyme was higher than in classical Morquio patients. Uronic acid, measured in precipitated GAG by the carbazole test, was increased in 23 of the 25 patients so tested. In the turbidity test at pH 7.0, values were increased in 24 of the 27 patients. In contrast, with the citrate-buffered (pH 4.8) turbidity measurement, GAG content was increased in only 19 of the 27 patients. This rapid and easy DMB method is a reliable screening procedure for mucopolysaccharidoses and compares well with procedures used hitherto.

Adolescent↗
PubMed1995

[Mucopolysaccharidoses--current aspects of diagnosis and therapy].

The mucopolysaccharidoses, first described at the beginning of this century, are still subject of research. The accumulation of pathological metabolites and the underlying enzyme defects are now correlated to specific gene mutations. A comparison of genotype and phenotype of the individual forms of the mucopolysaccharidoses is the subject of ongoing studies. In many cases, symptomatic treatment was not able to increase the quality of life of patients suffering from mucopolysaccharidosis to a satisfactory degree. International working groups are, thus, currently trying to improve and standardize symptomatic therapies. A causal therapeutic approach was attempted by implanting different cells and tissues that are able to produce the missing enzymes. Bone-marrow transplantations were also performed, but both treatment approaches were not very effective and in some cases even proved fatal for the patients. An intensive international research effort focuses on enzyme-replacement therapy and gene therapy. Mucopolysaccharidoses are rare diseases, affecting only about one hundred patients in Austria. Nevertheless, Austria plays an active role in researching these metabolic disorders.

Adult↗
PubMed1999

Children with mucopolysaccharidoses--three cases report.

The mucopolysaccharidoses (MPS) are a group of inherited disorders of metabolism, with widespread, progressive involvement and derangement of many organs and tissues. Because of their disabling nature, frequent surgical intervention for the abnormality entailed is common, and is associated with a high degree of anesthetic risks perioperatively. One of the major hazards which we find clinically is airway difficulty. Multiple factors are present in the mucopolysaccharidoses to make airway management and trachael intubation potentially hazardous. Aside from generalized infiltration and thickening of the soft tissues, the oropharynx may be obstructed by a large tongue with tonsillar hypertrophy. Also, the friable mucosa covering the nasal and oral pharynx renders these structures easily to bleed and edematous. The neck is typically short and immobile, and the cervical spine and tempromandibular joint may have a limited range of movement. From our experience, we have learned not to overlook the propensity of airway difficulty. The uniqueness of their anatomy and extremely sensitive airway often result in failed intubation and bronchospasm even after successful intubation. Recently, in Mackay Memorial Hospital we have encountered in series three pediatric cases with mucopolysaccharidoses (one Hurler and two Hunter syndromes). In this report we would like to share our experiences and to discuss the anesthetic risks and management of the MPS patients.

Anesthesia↗
PubMed1988

The mucopolysaccharidoses and anaesthesia: a report of clinical experience.

Patients with the mucopolysaccharidoses show widespread, progressive involvement and derangement of many organs and tissues which can have profound implications for the anaesthetist. These disorders are uncommon and few anaesthetists care for these patients on a regular basis although individual patients often undergo multiple anaesthetics for procedures intended to improve their quality of life. There is a relative paucity of literature dealing with clinical anaesthetic experience with these patients. We report a retrospective review of the recent experience at the Children's Hospital of Eastern Ontario in Ottawa, Canada, administering 38 anaesthetics to nine patients with several of the mucopolysaccharidoses; specifically the Hunter, Hurler, Sanfilippo and Morquio syndromes. The establishment and maintenance of an adequate airway represents the most commonly encountered anaesthetic-related problem in these patients. We found an overall incidence of airway-related problems of 26 per cent. In patients with the Hurler or Hunter syndromes the incidence of airway-related problems was 53 per cent.

Age Factors↗