scholarly journals Mucopolysaccharidosis Type I in Children, a Forgotten Diagnosis Responsible for Undiagnosed Musculoskeletal Complaints: Report of Two Cases

2019 ◽  
Vol 62 (4) ◽  
pp. 161-165
Author(s):  
Soheila Hoseinzadeh Moghadam ◽  
Masood Ghahvechi ◽  
Fatemeh Mozafari ◽  
Fatemeh Sayarifard ◽  
Mahdieh-Sadat Mousavi ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Type I ◽  
Musculoskeletal Complaints ◽  
Lysosomal Storage ◽  
Multiple Systems ◽  
Enzyme Replacement ◽  
Presenting Symptoms ◽  
Key Factor ◽  
Delays In Diagnosis ◽  
Clinical Conditions

Mucopolysaccharidoses (MPS) are a subgroup of lysosomal storage disorders. The underlying mechanism of MPS disorders are deficiency in specific enzymes which leads to accumulation of partially degraded glycosaminoglycans (GAGs) in various tissues. A wide variety of manifestations are reported but musculoskeletal complaints are common among them. In milder forms of MPS, musculoskeletal complaints are presenting symptoms. Delays in diagnosis due to unspecific and mild symptoms is common. Misdiagnosis of MPS as juvenile idiopathic arthritis and other inflammatory arthritis disorders is frequent. Early diagnosis and treatment prevents irreversible cellular damages and is a key factor in efficacy of enzyme replacement therapy. In this study we described two MPS patients with musculoskeletal complaints who were not diagnosed for a period of time. Although musculoskeletal manifestation are common in a variety of clinical conditions, their presence at low ages or co-occurrence of other manifestations (such as cardiac, respiratory, neurologic, etc.) in multiple systems should prompt evaluation of patients for MPS and other metabolic disorders. The rheumatologists’ awareness on MPS should be promoted to achieve timely diagnosis and subsequent early treatment.

scholarly journals REDUCED DOSING REGIMEN OF ENZYME REPLACEMENT THERAPY IN ADULT PATIENTS WITH TYPE I GAUCHER DISEASE: PRELIMINARY RESULTS

2019 ◽  
Vol 64 (3) ◽  
pp. 331-341 ◽  
Author(s):  
R. V. Ponomarev ◽  
K. A. Lukina ◽  
E. P. Sysoeva ◽  
R. B. Chavynchak ◽  
A. A. Solovyeva ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gaucher Disease ◽  
Lysosomal Storage Diseases ◽  
Adult Patients ◽  
Type I ◽  
Treatment Goals ◽  
Lysosomal Storage ◽  
Current Standard ◽  
Enzyme Replacement

Introduction. Gaucher disease (GD) belongs to the group of lysosomal storage diseases. Enzyme replacement therapy (ERT) is considered to be the current standard in GD treatment. No reduced ERT regimen has thus far been developed. Aim. To develop an optimal reduced ERT regimen for adult patients with type I GD, which is scientifically and economically viable.Materials and methods. The study included 100 adult patients with type I GD who achieved treatment goals following at least two years of the standard ERT regimen. Patients were prescribed a reduced ERT regimen, which consisted in increasing the interval between the infusions of the recombinant enzyme up to 4 weeks, at a dose of 15–20 units/kg of body weight. The efficacy of the reduced ERT regimen was assessed once every 12 months according to main GD parameters. The follow-up period in the study ranged from 12 to 36 months.Results. The patients with type I GD who achieved treatment goals following the standard ERT regimen and were then prescribed a reduced ERT regimen retained a stable therapeutic effect of the initial treatment according to all parameters: no clinically significant differences found in haemoglobin and platelet levels, spleen size and specific infiltration of femur bone marrow.Conclusion. An increase in the intervals between infusions of the recombinant glucocerebrosidase up to 4 weeks for 12, 24 and 36 months did not lead to worsening of the laboratory and instrumental parameters associated with GD. 

scholarly journals Gaucher Disease Type I: A Case Report

2020 ◽  
Vol 47 (3) ◽  
pp. 22-25
Author(s):  
D. Nikolova ◽  
A. Yordanov ◽  
V. Damyanova ◽  
A. Yavorova ◽  
A. Radinov
Keyword(s):  
Gaucher Disease ◽  
Clinical Symptoms ◽  
Systemic Disease ◽  
Disease Type ◽  
Type I ◽  
Lysosomal Storage ◽  
Laboratory Findings ◽  
Enzyme Replacement ◽  
Targeted Analysis ◽  
Laboratory Test Results

AbstractGaucher disease (GD) is a multi-systemic disease with a low population frequency. It is a lysosomal storage disorder (LSD) that causes accumulation of glucocerebroside in the so called Gaucher cells predominantly in areas like the spleen, liver and bone marrow. Type I GD (GDI) is the most common form and usually does not involve the brain and the spinal cord. The symptoms can range from mild to severe and may appear anytime from childhood to adulthood. Diagnostics can often be challenging and imposes looking at person’s medical history, symptoms, physical exam, and laboratory test results. We present a difficult to diagnose case of a 34-year-old woman admitted to the Clinic of Hematology, “Sv. I. Rilski” hospital with splenomegaly, normal laboratory findings and non-enlarged liver. She didn’t show focal neurological symptoms. A series of tests were assigned including genetic targeted analysis. The case is an example of a rare genetic disease with mild clinical symptoms. Diagnosis of Gaucher disease, type I was confirmed by measurement of a GBA enzyme activity and identification of mutations in the GBA gene inherited in an autosomal recessive manner. Thanks to the efforts of the clinical team, the assignment of adequate clinical and laboratory tests and their correct interpretation, the patient was subjected to enzyme replacement therapy (ERT). Although the diagnosis was settled relatively late (at 34 years of age), the correct therapy slowed down the invalidation and improved the quality of life of the patient.

scholarly journals Differences in MPS I and MPS II Disease Manifestations

2021 ◽  
Vol 22 (15) ◽  
pp. 7888
Author(s):  
Christiane S. Hampe ◽  
Brianna D. Yund ◽  
Paul J. Orchard ◽  
Troy C. Lund ◽  
Jacob Wesley ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Treatment Options ◽  
Neurological Involvement ◽  
Type I ◽  
Ionic Balance ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Corneal Clouding ◽  
Mps I

Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.

scholarly journals From Symptoms and Signs to Diagnosis in a Rare Disease, Type I Gaucher Disease

2018 ◽  
Vol 15 (1) ◽  
pp. 69-76
Author(s):  
Mihaela Ghinea ◽  
Sabina Ciocodei ◽  
Gabriela Butoi ◽  
Geandan Memet ◽  
Andreea Stoica ◽  
...  
Keyword(s):  
Laboratory Testing ◽  
Gaucher Disease ◽  
Storage Disease ◽  
Disease Type ◽  
Genetic Mutations ◽  
Type I ◽  
Lysosomal Storage ◽  
Specific Enzyme ◽  
Enzyme Replacement ◽  
Symptoms And Signs

AbstractGaucher disease is the most frequent lysosomal storage disease, caused by the deficiency of an enzyme called β-glucocerebrosidase. Three types of Gaucher disease are described. Type I Gaucher disease benefits from lifelong enzyme replacement therapy with imiglucerase.Herein, we present the case of a 34-year-old female patient, a commercial worker, who was admitted to our Department of Haematology in the Emergency Clinical Hospital of Constanta in order to investigate the aetiology of a persistent splenomegaly. Clinical examination and laboratory testing evidenced the following: splenomegaly, hepatomegaly, anaemia, leukopenia and neutropenia, thrombocytopenia, and a myelogram showing Gaucher cells. In this context, the suspicion of Gaucher disease was raised and the investigations were further completed through specific enzyme testing and genetic testing. The low values of lysosomal enzymes, coupled with the detection of two specific genetic mutations confirmed the diagnosis of Gaucher disease.In January 2017, treatment with 2400U of imiglucerase in intravenous perfusion every two weeks was begun.

scholarly journals Ophthalmological Findings in Mucopolysaccharidoses

2019 ◽  
Vol 8 (9) ◽  
pp. 1467 ◽  
Author(s):  
Shizuka Tomatsu ◽  
Susanne Pitz ◽  
Ulrike Hampel
Keyword(s):  
Focal Point ◽  
Childhood Mortality ◽  
Research Progress ◽  
Type I ◽  
Lysosomal Storage ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Ocular Manifestations ◽  
Corneal Clouding ◽  
Low Incidence

The mucopolysaccharidoses (MPS) are a heterogenous group of lysosomal storage disorders caused by the accumulation of glycosaminoglycans (GAGs). The accrual of these compounds results in phenotypically varied syndromes that produce multi-organ impairment with widespread systemic effects. The low incidence of MPS (approximately 1/25,000 live births) in conjunction with the high childhood mortality rate had limited the availability of research into certain clinical features, especially ocular manifestations. As the recent successes of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) have greatly increased life expectancy in these patients, they have served as a focal point for the transition of research towards improvement of quality of life. Ophthalmological findings in MPS include corneal clouding, glaucoma, optic neuropathies, and retinopathies. While corneal clouding is the most common ocular feature of MPS (especially type I, IVA, and VI), its response to HSCT and ERT is minimal. This review discusses known eye issues in the MPS subtypes, diagnosis of these ocular diseases, current clinical and surgical management, noteworthy research progress, and ultimately presents a direction for future studies.

Evidence that glycosaminoglycan storage and collagen deposition in the cauda epididymidis does not impair sperm viability in the Mucopolysaccharidosis type I mouse model

2020 ◽  
Vol 32 (3) ◽  
pp. 304 ◽  
Author(s):  
Cinthia Castro do Nascimento ◽  
Odair Aguiar ◽  
Gustavo Monteiro Viana ◽  
Vânia D'Almeida
Keyword(s):  
Sperm Morphology ◽  
Reproductive Age ◽  
Morphologic Change ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Cauda Epididymidis ◽  
Mps I

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by a deficiency of the lysosomal hydrolase, α-L-iduronidase (IDUA). IDUA degrades heparan and dermatan sulfates, two types of glycosaminoglycan (GAG), important signalling and structural molecules of the extracellular matrix. Because many cell types store GAGs, MPS I has been investigated in human and animal models. Enzyme replacement therapy is available for MPS I patients and has improved their life expectancy, allowing them to achieve reproductive age. The aim of this study was to evaluate epididymal and sperm morphology and function in a murine model of MPS I. We used C57BL Idua+/+ and Idua−/− adult male mice (6 months old) to investigate epididymal morphology, sperm ultrastructure, GAG characterisation and mating competence. Epithelial GAG storage, especially in the cauda epididymidis, was seen in Idua−/− mice. Regardless of the morphologic change and GAG storage found in the cauda epididymis, sperm morphology and motility were normal, similar to wild types. In the interstitium, vacuolated cells were found in addition to deposits of GAGs. Mating was not impaired in Idua−/− males and litter sizes were similar between groups. At the time point of the disease evaluated, the deficiency in IDUA affected the morphology of the epididymis in male Idua−/− mice, whereas sperm appearance and motility and the male’s capacity to mate and impregnate females were preserved.

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

2019 ◽  
Vol 103 (3) ◽  
pp. 315-326 ◽  
Author(s):  
Aaron W Winter ◽  
Ali Salimi ◽  
Luis H Ospina ◽  
Jonathan C P Roos
Keyword(s):  
Gaucher Disease ◽  
Substrate Reduction Therapy ◽  
Type I ◽  
Lysosomal Storage ◽  
Ocular Abnormalities ◽  
Enzyme Replacement ◽  
Ocular Manifestations ◽  
Ophthalmic Manifestations ◽  
Increased Risk ◽  
Risk Of Malignancy

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme’s metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher’s can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 – present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

scholarly journals Echocardiographic features and behavior of cardiac structural abnormalities in mucopolysaccharidosis

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
S Saba ◽  
A Al Sergani ◽  
O Vriz ◽  
N Kholaif ◽  
K Ramzan ◽  
...  
Keyword(s):  
Severe Case ◽  
Marrow Transplant ◽  
Adult Patients ◽  
Type I ◽  
Lysosomal Storage ◽  
Adult Age ◽  
Enzyme Replacement ◽  
Funding Sources ◽  
Type Iv ◽  
Reduced Mobility

Abstract Funding Acknowledgements Type of funding sources: None. Mucopolysaccharidosis (MPS) is a rare genetic lysosomal storage disorder with a wide variability of phenotype. A systematic descriptive study dealing with the echocardiographic (E) features of valvular involvement and their evolution over the time in adolescent and adult patients, whose number is growing up in adult echocardiographic laboratory, is lacking in the medical literature. Purpose To detect the E features of valvular involvement and their evolution in adolescent and adult patients. Method Study design: observational descriptive retrospective. Study group: 142 E studies in 17 adolescent and adult patients with diagnosis of MPS from 2001 until 2020. Mitral (M), aortic (A), tricuspid (T) valves (V) E features (thickness, mobility, calcification, and function), their evolution over the time and the behaviour with Enzyme replacement therapy (ERT) or bone marrow transplant (BMT) were assessed. Result 52% male, mean age 21 yrs ranges 16 to 48 yrs. 5% of the patient had MPS type I, 11% MPS type II, 29% MPS type IV, and 52% MPS type VI. 70% received ERT and 11% BMT. In the severe case all the valves were involved (panel A, B, C; white arrows point to valve leaflets; yellow arrows MV apparatus) the whole MV apparatus was involved since the earlier stage and in the latest stage the calcification was massive (panel C). The predominant valvular dysfunction was the regurgitation followed by mixed disorder while the most frequent severe lesion was the stenosis; the echocardiographic pattern differs from the classical hockey stick appearance of the early phase of rheumatic MV and the thickening is different from the myxomatous MV for the reduced mobility and the presence of calcification. The reduced mobility of the TV (panel C) also differs from the Loeffler syndrome because of the restriction of the leaflets and the association with thickening and calcification. Under treatment, the MV thickening was found to have a slow progression of less than 1 mm yearly in 61% cases. Conclusion Our results showed that all the valves are affected mainly the MV; the echocardiographic pattern of MPS, different from other valvular diseases of adolescent and adult age, can help in avoiding misdiagnose. Our observations also suggest that the cardiac involvement show slow rate of progression after the initiation of the therapy. Further studies are required to confirm our results. Type of valve % of valve thickness % of reduced mobility % calcification diffuse % valve lesion Mitral valve 88% 65% 47% 75% Aortic valve 76% 23% 41% 57% Tricuspid valve 82% 47% 17% 52% Abstract Figure. Echocardiographic features

Hallazgos oftalmológicos en enfermedad de Fabry: relación de su severidad en una familia mexicana

2019 ◽  
Vol 1 (1) ◽  
pp. 43-49
Author(s):  
Araceli Borja Borja ◽  
Gabriela Salas Pérez ◽  
Pablo Radillo Díaz
Keyword(s):  
Premature Mortality ◽  
Retinal Vessel ◽  
Multiple Organ ◽  
High Morbidity ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Non Invasive ◽  
High Incidence ◽  
Cornea Verticillata ◽  
Gla Gene

Introduction. Fabry disease (FD) is a lysosomal storage disorder associated with multiple organ dysfunction which eventually leads to high morbidity and premature mortality. Ophthalmologic findings in FD are very common and have been described extensively. We describe the ophthalmologic findings of a family diagnosed with FD at Hospital de Especialidades de Puebla and establish their relationship with other phenotypic findings. Cases Presentation. A renal, cardiac, audiological, neurological, and ophthalmologic evaluation was carried out. The disease was confirmed by GLA gene sequencing. The ophthalmologic assessment was focused on the changes described in the literature, as well as the search for other anomalies possibly related to the disease. All the patients had the c.260delA (P.Glu87Glyfs*34) mutation in the GLA gene. The main ophthalmologic finding in our patients was cornea verticillata (in 100 % of the female patients). Other ophthalmologic manifestations were dry eye, retinal vessel tortuosity, ametropia, chromatic vision disorders, ocular annexes, eyelids, and conjuntiva disorders. Conclusions. Most of the assessed patients showed ophthalmologic changes, consistent with the results described in the literature. A remarkable finding in the sample was the high incidence of changes in women, in whom one would not expect the disease to be as severe because they are heterozygous. Ophthalmologic abnormalities in FD require deeper evaluation to establish their possible use as markers of disease progression and/or enzyme replacement therapy initiation due to the benefit of the non-invasive nature of ophthalmologic evaluations.

RESPONSE TO ENZYME REPLACEMENT THERAPY IN PATIENTS WITH GAUCHER DISEASE TYPE I

2019 ◽  
Vol 22 (06) ◽  
pp. 103-117
Author(s):  
Mays Al-Tai ◽  
Deia Al-Asady ◽  
Rula Hamid
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gaucher Disease ◽  
Disease Type ◽  
Type I ◽  
Enzyme Replacement
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