A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients-A Qualitative and Quantitative Approach.

Chitotriosidase is an enzyme produced and secreted in large amounts by activated macrophages, especially macrophages loaded with phagocytozed glycosphingolipid in Gaucher disease. Macrophages phagocytose decayed blood cells that contain a lot of sphingolipid-rich cell membranes. In Gaucher disease, due to a deficit in beta-glucocerebrosidase activity, the phagocytozed substrate glucocerebroside cannot undergo further catabolism.

Prevalence rates of mucopolysaccharidoses in Poland.

The aim of this study was to determine the prevalence rates of mucopolysaccharidoses in Poland and to compare them with other European countries. A retrospective epidemiological survey covering the period between 1970 and 2010 was implemented. Multiple ascertainment sources were used to identify affected patients.

A case report of 'variant' biochemical phenotype of Niemann-Pick C disease and a discussion of therapeutic options.

Niemann-Pick disease type C is a rare hereditary disorder caused by mutation-disrupted metabolism of cholesterol and low-density lipoprotein (LDL). In most patients, symptoms begin in childhood with severe clinical progression. We present a patient with heterozygote mutations 3001A>G and 3019C>G with late onset of the disease and positive response to treatment with miglustat.

Gastrointestinal phenotype of fabry disease in a patient with pseudoobstruction syndrome.

Fabry disease is a rare, X-linked inborn error of glycosphingolipid metabolism caused by a deficiency of the lysosomal enzyme α-galactosidase A. Progressive deposition of GL-3 starts early in life, presumably as early as in fetal life. Chronic burning or provoked attacks of excruciating pain in hands and feet in Fabry disease are common in most children as well as GI-symptoms.

Mucopolysaccharidosis type II in females and response to enzyme replacement therapy.

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase (IDS). Two affected girls with moderate and severe forms of MPS II with normal karyotypes and increased urinary dermatan sulphate and heparin sulphate excretion and marked deficiencies of IDS activity are reported. Molecular studies showed that case 1 has a heterozygous mutation c.

Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia.

Mucopolysaccharidosis VI (MPS VI) is a rare autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB). Over 130 ARSB gene mutations have been identified thus far and most mutations are unique to individual families. We aimed to analyze the spectrum of mutations in the ARSB gene responsible for the disorder in Poland, Belarus and Baltic States.

Gaucher's disease in Lithuania: its diagnosis and treatment.

Gaucher's disease is a lysosomal storage disease caused by the lack of beta-glucocerebrosidase enzyme, leading to the accumulation of glucocerebroside. Gaucher's disease is the most frequent type of sphingolipidosis as well as the most frequent lysosomal disease. Clinically, two forms of Gaucher's disease are defined: nonneuronopathic form, so-called type 1, characterized by hepatosplenomegaly, thrombocytopenia, anemia, and osteopenia, and neuronopathic form, known as types 2 and 3, which are also characterized by hepatosplenomegaly, hematological and bone changes; however, involvement of the central nervous system dominates in the clinical picture.

Gaucher disease due to saposin C deficiency, previously described as non-neuronopathic form--no positive effects after 2-years of miglustat therapy.

Gaucher disease occurs mainly as a result of a deficiency of the lysosomal enzyme beta-glucocerebrosidase activity. A rare variant form of Gaucher disease is known in which saposin C required for glucosylceramide degradation is deficient. In an earlier paper we described the first cases of two siblings with the non-neuronopathic form of Gaucher disease caused by saposin C deficiency [Tylki-Szymańska et al.

Improvement in the range of joint motion in seven patients with mucopolysaccharidosis type II during experimental gene expression-targeted isoflavone therapy (GET IT).

Mucopolysaccharidosis type II (MPS II, Hunter disease) is an X chromosome-linked inherited metabolic disease caused by mutations resulting in deficiency of activity of iduronate-2-sulfatase (IDS) and accumulation of undegraded glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate. Previous experiments with cell cultures and studies on animal model of MPS II suggested that gene expression-targeted isoflavone therapy (GET IT), based on genistein-mediated reduction of efficiency of GAG synthesis, might be a suitable therapy for this disease. In this report, we demonstrate efficacy of GET IT in connective tissue elasticity, particularly in improving the range of joint motion in seven patients with MPS II after 26 weeks of treatment with an isoflavone extract at the dose corresponding to 5 mg/kg/day of genistein.

[Diagnostic problems in a 17-year-old patient with gastrointestinal manifestations of Fabry disease].

Fabry disease is a rare X-linked recessive lysosomal storage disorder caused by deficiency of lysosomal enzyme alpha-galactosidase, which leads to accumulation of globotriasylceramides (GL-3) in visceral tissues and vascular endothelium, causing multi-organ failure. We presenta case of Fabry disease in a 17-year-old patient with mainly gastrointestinal manifestations, diagnosed 10 years after the manifestation of first symptoms. Significant and progressive weight loss with abdominal pain and vomiting, leading to cachexia, were observed in early childhood.

Gaucher disease diagnosed after bone marrow trephine biopsy - a report of two cases.

The hematologist is at the forefront of specialists to whom patients with Gaucher disease present because of cytopenia and hepatosplenomegaly. Usually, patients with such symptoms have undergone trephine biopsy. We present the cases of two patients in whom Gaucher disease was suspected because of the discovery of Gaucher cells in trephine biopsy, and subsequently confirmed via enzymatic and molecular investigations.

Substrate inhibition of lysosomal hydrolases: α-Galactosidase A and β-glucocerebrosidase.

Objective: We have investigated the kinetics of α-galactosidase A and β-glucocerebrosidase deficient in Fabry and Gaucher diseases, respectively.

Design And Methods: We have performed spectrofluorymetric measurements of the activity of enzymes using a derivative of 4-methylumbelliferone as a substrate and a human T-cell line as a source of enzymes.

Results: We have observed the substrate inhibition effect, which is related to temperature.

Two-year follow-up of Sanfilippo Disease patients treated with a genistein-rich isoflavone extract: assessment of effects on cognitive functions and general status of patients.

Background: Mucopolysaccharidoses (MPS) are inherited metabolic disorders caused by deficiencies in enzymes involved in degradation of glycosaminoglycans. MPS type III (Sanfilippo disease) is clinically characterized mainly by progressive and severe behavioral disturbances and cognitive dysfunction. Recent 1-year experimental treatment of 10 patients with a genistein (4', 5, 7-trihydroxyisoflavone)-rich extract resulted in improvement of tested parameters, including cognitive and behavioral functions.

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations.

Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported.

Efficacy of recombinant human alpha-L-iduronidase (laronidase) on restricted range of motion of upper extremities in mucopolysaccharidosis type I patients.

The aims of the study were to assess the effectiveness of enzyme replacement therapy (ERT) with laronidase on the range of motion (ROM) of upper extremities and influence on activities of daily living (ADLs) of patients with mucopolysaccharidosis type I (MPS I). The ROM of 17 patients with MPS I was followed from the first year of life until the introduction of ERT and after 52-208 weeks of treatment. In all patients (group 1, n = 10), passive ROM was assessed.

Anthropometric data of 14 patients with mucopolysaccharidosis I: retrospective analysis and efficacy of recombinant human alpha-L-iduronidase (laronidase).

Objectives: Our goal was to evaluate growth patterns in terms of body height, weight, head and chest circumference in patients with mucopolysaccharidosis type I (MPS I) without treatment and after enzyme replacement therapy (ERT) with alpha-l-iduronidase (laronidase).

Patients And Methods: Anthropometric features of 14 patients with MPS I were followed from birth until the introduction of ERT (group 1-1st year of life, group 2 3rd year of life), after 52-260 weeks of ERT and periodically during treatment. The data since birth until beginning of treatment was obtained by retrospective review of patients' charts.

Correlation between severity of mucopolysaccharidoses and combination of the residual enzyme activity and efficiency of glycosaminoglycan synthesis.

Aim: To develop a method for prediction of severity and clinical course of mucopolysaccharidoses (MPS), a group of inherited metabolic diseases.

Methods: Various biochemical and clinical parameters (including estimation of the level of clinical severity, presence of specific mutations, residual enzyme activity, urinary glycosaminoglycan (GAG) excretion, storage of GAG in fibroblasts and efficiency of GAG synthesis) of patients suffering from MPS types II, IIIA and IIIB were determined. Correlations between genetic, biochemical and clinical parameters were tested.

Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients.

Background: Mucopolysaccharidoses (MPSs) are a group of severe metabolic disorders caused by deficiencies in enzymes involved in the degradation of glycosaminoglycans (GAGs)-long chains of sugar carbohydrates in cells that help build bone, cartilage, tendons, corneas, skin, and connective tissue. Although enzyme replacement therapy has become available for the treatment of some types of MPS, effective treatment of neurodegenerative forms of MPS has yet to be determined. Recently, genistein (4',5,7-trihydroxyisoflavone), a specific inhibitor of protein tyrosine kinase, has been found to inhibit GAG synthesis and to reduce GAG concentrations in cultures of fibroblasts of MPS patients.

[Fabry's disease: a clinical case and literature review].

Fabry's disease is a congenital disorder of glycosphingolipid metabolism with an X-linked recessive inheritance, presenting with typical symptoms of pain crises, acroparesthesias, cutaneous and mucosal angiokeratomas, hypohidrosis, heart and kidney lesions, and other symptoms, which are described below. From 2001, this disease is one of inborn errors of metabolism in which enzyme replacement therapy is applied very effectively. Two atypical forms of the disease were discovered, and the first surveys were done revealing that the incidence of Fabry's disease can be much more higher than it was considered before.

Abnormalities in the hair morphology of patients with some but not all types of mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) are a group of inherited, progressive, metabolic diseases, caused by the deficiency of one of the enzymes involved in the degradation of glycosaminoglycans (GAGs). The disease is usually fatal, with the life span of most untreated MPS patients being between one and two decades. In this report, on the basis of scanning electron microscopy (SEM) studies, we demonstrate that, besides the many other symptoms of MPS, there are characteristic abnormalities in the hair morphology of patients suffering from some types of this disease (MPS I, MPS II, MPS IIIA, MPS IIIB), but not from other types (MPS IVA, MPS IVB, MPS VI), where the changes are minor, if any.

Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) are inherited, severe, progressive, metabolic disorders caused by deficiencies in different enzymes involved in degradation of glycosaminoglycans (GAGs). Although enzyme replacement therapy (ERT) has recently been available for MPS type I, and clinical trials have been performed in ERT for MPS II and MPS VI, there is little chance that this kind of treatment may be effective for neurodegenerative forms of MPS (due to inefficient delivery of enzymes to central nervous system through the blood-brain barrier), hence currently there is no effective therapy available for them. Therefore, we aim to develop an alternative therapy for these diseases.

Serum hyaluronidase aberrations in metabolic and morphogenetic disorders.

Hyaluronidases are endo-glycosidases that degrade both hyaluronan (hyaluronic acid) (HA) and chondroitin sulfates. Deficiency of hyaluronidase activity has been predicted to result in a phenotype similar to that observed in mucopolysaccharidosis (MPS). In the present study, we surveyed a variety of patients with phenotypes similar to those observed in MPS, but without significant mucopolysacchariduria to determine if some are based on aberrations in serum hyaluronidase (Hyal-1) activity.

Changes in hair morphology of mucopolysaccharidosis I patients treated with recombinant human alpha-L-iduronidase (laronidase, Aldurazyme).

Mucopolysaccharidoses (MPS) are heritable, metabolic diseases caused by accumulation of mucopolysaccharides (glycosaminoglycans, GAGs) in lysosomes. This accumulation is due to a deficiency in one of several specific enzymes involved in the degradation of GAGs. MPS type I (MPS I) is caused by low or undetectable activity of alpha-L-iduronidase, an enzyme involved in removing the terminal iduronic acid residues from heparan and dermatan sulfate.