Considering the advances made on mucopolysaccharidosis type I after the consensus study published by a group of experts in Argentina in 2008, recommendations about genetic testing, cardiological ...follow-up, airway care, hearing impairment detection, spinal and neurological conditions, as well as current treatments, were reviewed. Emphasis was placed on the need for early diagnosis and treatment, as well as an interdisciplinary follow-up.
There are currently two available enzyme replacement therapies for Fabry disease and little information regarding efficacy and safety of switching therapies. Between 2009 and 2012 there was a ...worldwide shortage of agalsidase beta and patients on that enzyme were switched to agalsidase alfa. This retrospective observational study assessed a 2-year period of efficacy and safety in a population of Fabry patients, in Argentina (30 patients) and Venezuela (3 patients), who switched therapies from algasidase beta to agalsidase alfa. Thirty-three patients completed 24-months follow-up after the switch (age 32.4 ± 2.0, range 10.0-55.9 years; male: female 23:10). Measures of renal function such as estimated glomerular filtration rate remained almost unchanged in 31 patients without end stage renal disease over the 2 years after switching and urine protein excretion continued stable. Cardiac functional parameters: left ventricular mass index, interventricular septum, left ventricular posterior wall showed no significant change from baseline in the 33 patients. Quality of life, pain and disease severity scores were mostly unchanged after 24-months and agalsidase alfa was generally well tolerated. Our findings showed there is no significant change in the efficacy measured through the renal or cardiac function, quality of life, pain, disease severity scoring and safety for at least 2 years after switching from agalsidase beta to agalsidase alfa.
Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders, leading to the progressive accumulation of glycosaminoglycans (GAGs) and the subsequent compromising of tissues and organ ...malfunction. Although incurable, most types of MPS can be treated with enzyme replacement therapy (ERT), an approach that has had positive effects on the natural clinical evolution and which impact has been extensively investigated. Unfortunately, to date, there is relatively little data regarding the effects of ERT interruption, especially in Latin America, where such interruption may be frequent due to a variety of issues (for instance, difficulties involving logistics, reimbursement and/or payment withdrawal).
A group of medical professionals from Latin America with experience in Genetics, Pediatrics and Neurology held an Advisory Board Meeting in the city of São Paulo, in October 2018, to discuss the issue of ERT interruptions in the region and recommendations to health care professionals on how to deal with these interruptions and better assess the therapeutic effects of ERT.
Recommendations provided by the experts may support physicians in dealing with the most common reasons for ERT interruptions in Latin America. Most importantly, recommendations for data collection at specific timepoints (at baseline, throughout the treatment and during the interruption period of ERT and after its resumption) can significantly improve the collection of real world evidence on the effects of ERT and its interruptions, supporting health care professionals and policy makers in the decision making regarding the provision of these therapies for MPS patients.
•Positive impact of ERT is reported in MPS patients, but the effects of its interruption is overlooked.•In Latin America, ERT interruption is not infrequent. A systematic evaluation the worsening of MPS progression is vital.•The proposed structured data collection would help to evaluate patients and generate real word data.•We encourage studies and experts discussions for a better understand the value of ERT for MPS patients in Latin America.
Epilepsy in mucopolysaccharidosis disorders Scarpa, Maurizio; Lourenço, Charles Marques; Amartino, Hernán
Molecular genetics and metabolism,
December 2017, 2017-12-00, 20171201, Letnik:
122
Journal Article
Recenzirano
Odprti dostop
The mucopolysaccharidosis (MPS) disorders are caused by deficiencies of specific lysosomal enzymes involved in the catabolism of glycosaminoglycans (GAGs). The resulting GAG accumulation in cells and ...tissues throughout the body leads to progressive multi-organ dysfunction. MPS patients present with several somatic manifestations, including short stature, musculoskeletal abnormalities, and cardiorespiratory dysfunction, and several primary and secondary neurological signs and symptoms. Epileptic seizures are neurological signs of MPS thought to develop due to accumulation of GAGs in the brain, triggering alterations in neuronal connectivity and signaling, and release of inflammatory mediators. The amount of literature on the prevalence, pathophysiology, clinical features, and management of epileptic seizures in patients with MPS is limited. This review discusses current knowledge on this topic, as well as two case examples, presented and discussed during a closed meeting on MPS and the brain among an international group of experts with extensive experience in managing and treating MPS.
The mucopolysaccharidosis (MPS) disorders are ultra-rare lysosomal storage disorders associated with progressive accumulation of glycosaminoglycans (GAGs) in cells and tissues throughout the body. ...Clinical manifestations and progression rates vary widely across and within the different types of MPS. Neurological symptoms occur frequently, and may result directly from brain damage caused by infiltration of GAGs, or develop secondary to somatic manifestations such as spinal cord compression, hydrocephalus, and peripheral nerve entrapment. Management of secondary neurological manifestations often requires surgical correction of the underlying somatic cause. The present review discusses the surgical management of neurological disease in patients with MPS, including diagnostic imaging. Background information is derived from presentations and discussions during a meeting on the brain in MPS, attended by an international group of experts (April 28–30, 2016, Stockholm, Sweden), and additional literature searches.
Pompe disease is a rare, autosomal recessive disorder characterized by deficiency of lysosomal acid alpha-glucosidase and accumulation of lysosomal glycogen in many tissues. The variable clinical ...manifestations, broad phenotypic spectrum, and overlap of signs and symptoms with other neuromuscular diseases make diagnosis challenging. In the past, the diagnosis of Pompe disease was based on enzyme activity assay in skin fibroblasts or muscle tissue. In 2004, methods for measuring acid alpha-glucosidase activity in blood were published. To compare how diagnostic methods changed over time and whether they differed by geographic region and clinical phenotype, we examined diagnostic methods used for 1059 patients enrolled in the Pompe Registry in three onset categories (Group A: onset of signs/symptoms ≤12months of age with cardiomyopathy; Group B: onset ≤12months without cardiomyopathy and onset >1year to ≤12years; Group C: onset >12years). Enzyme activity-based assays were used more frequently than other diagnostic methods. Measuring acid alpha-glucosidase activity in blood (leukocytes, lymphocytes, or dried-blood spot) increased over time; use of muscle biopsy decreased. The increased use of blood-based assays for diagnosis may result in a more timely diagnosis in patients across the clinical spectrum of Pompe disease.
•Enzyme assays, DNA analysis and muscle biopsy were used for Pompe disease diagnosis.•Enzyme activity assays were used most often for diagnosing Pompe Registry patients.•Use of blood-based diagnostic assays increased and use of muscle biopsy decreased.•Increased use of blood-based assays may lead to more timely Pompe disease diagnosis.•Data from the Pompe Registry helps increase understanding of Pompe disease globally.
We discuss four cases of acid alpha-glucosidase deficiency (EC, 3.2.1.3/20) without evident symptoms of Pompe disease (OMIM No 232300) in individuals of Asian descent. In three cases, the deficiency ...was associated with homozygosity for the sequence variant c.1726G>A; 2065G>A in the acid alpha-glucosidase gene (GAA) translating into p.G576S; E689K. One of these cases was a patient with profound muscular atrophy, another had cardio-myopathy and the third had no symptoms. The fourth case, the mother of a child with Pompe disease, was compound heterozygote for the GAA sequence variants c.1726G>A; 2065G>A/c.2338G>A (p.W746X) and had no symptoms either. Further investigations revealed that c.1726A; 2065A is a common GAA allele in the Japanese and Chinese populations. Our limited study predicts that approximately 4% of individuals in these populations are homozygote c.1726A; 2065A. The height of this figure in contrast to the rarity of Pompe disease in Asian populations and the clinical history of the cases described in this paper virtually exclude that homozygosity for c.1726A; 2065A causes Pompe disease. As c.1726A; 2065A homozygotes have been observed with similarly low acid alpha-glucosidase activity as some patients with Pompe disease, we caution they may present as false positives in newborn screening programs especially in Asian populations.
Summary
Purpose: In children with symptomatic or idiopathic focal epilepsies, their disease may evolve into an epileptic encephalopathy related to continuous spike and wave during slow sleep (CSWS) ...or electrical status epilepticus during slow sleep (ESES). ESES syndrome implies serious risks of neuropsychologic impairment, and its treatment has frequently been disappointing. The aim of this study is to present our experience using sulthiame as add‐on treatment in 53 patients with ESES syndrome that was refractory to other antiepileptic drugs (AEDs).
Methods: Neurologic examinations, cerebral magnetic resonance imaging (MRI), and repeated prolonged sleep electroencephalography (EEG) studies were performed in all cases. Data about school achievements and or neuropsychological evaluations were obtained repeatedly during the follow‐up of 1.5–16 years. Sulthiame was added in doses ranging between 5 and 30 mg/kg/day.
Key Findings: Since add‐on of sulthiame, 10 of 28 patients in the symptomatic group became seizure free: 4 patients with normal EEG studies and 6 with residual spikes. Nine of 28 patients showed a significant reduction in number of seizures and presented spikes but no ESES on EEG. The other nine cases showed neither clinical nor EEG improvement. A striking result was that 3 of 11 children with unilateral polymicrogyria and ESES syndrome became seizure free, and in another six a significant improvement in frequency of seizures and in EEG abnormalities seemed to be related to the add‐on of sulthiame. Twenty‐one of the 25 patients in the idiopathic group became seizure free and without ESES in <3 months after add on of sulthiame. In two of the patients the changes were seen in a few days.
Significance: We understand that sulthiame may be effective as add‐on treatment in children with ESES syndrome.
Hunter syndrome (mucopolysaccharidosis II) is a rare X-linked lysosomal storage disease caused by deficiency of the enzyme iduronate-2-sulfatase. The condition is one of a group of disorders, the ...mucopolysaccharidoses, which all result in accumulation of glycosaminoglycans. Hunter syndrome is a chronic progressive disorder whose clinical manifestations vary widely in severity and involve multiple organs and tissues. In addition to developing somatic symptoms, patients having the neuronopathic form of the disease also display developmental delay and cognitive impairment in early childhood that progressively worsens and that is severely life-limiting. Patients are at risk of developing secondary neurological manifestations, including hydrocephalus, vision and hearing loss, carpal tunnel syndrome and spinal cord compression. Common findings from brain magnetic resonance imaging (MRI) scans and at autopsy include neurodegenerative changes in white matter, the corpus callosum and basal ganglia; enlargement of periventricular spaces; ventriculomegaly; closed cephaloceles; and tissue atrophy. Though at present there is no specific treatment for the neurodegenerative aspects of the disease, hydrocephalus, carpal tunnel syndrome and spinal cord compression can be managed surgically. Patients who have Hunter syndrome should receive coordinated care from a multidisciplinary team: in light of the extensive neurological symptoms of the disease, neurologists play an important role in the diagnosis and management of this condition.
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