Misdiagnosis in mucopolysaccharidoses

Wiśniewska, Karolina; Wolski, Jakub; Gaffke, Lidia; Cyske, Zuzanna; Pierzynowska, Karolina; Węgrzyn, Grzegorz

doi:10.1007/s13353-022-00703-1

Cited by 19 publications

(22 citation statements)

References 99 publications

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“…Because of the lack of specific and efficient therapy, and due to severity of the disease, [1][2][3][4][5] it is crucial to make accurate diagnosis of Sanfilippo syndrome as early as possible to start to manage numerous problems relative early in patient's life. Although the biochemical and genetic diagnosis can be unequivocal by determining urinary/plasma HS levels, measuring activity of specific lysosomal enzyme (see Table 1) in leukocytes or fibroblasts, and identifying specific mutations, 2,7,15,62,63 the rarity of MPS III and variability of early symptoms make the proper diagnosis challenging. In fact, it is common that it takes a few or even several years to diagnose Sanfilippo disease.…”

Section: Importance Of Accurate Diagnosis and Diagnostic Problems In ...mentioning

confidence: 99%

“…Such a clinical picture of MPS III patients may cause misdiagnosis, especially at the early or middle stages of the disease. 7,64 The most often false suspicion is autism spectrum disorders (ASD), predominantly due to similarities of some symptoms of both diseases. 64,66 Another quite common diagnostic error is prediction of attention deficit/hyperactivity disorder (ADHD).…”

Section: Dovepressmentioning

confidence: 99%

“…69 In fact, a diagram for the diagnostic procedures towards MPS has been proposed recently. 7 However, Sanfilippo syndrome is a somewhat quaint type of this disease due to the extremely severe neurological component and relative mild somatic defects; thus, special care must be taken when suggesting a specific neurodegenerative disease in a child. Therefore, perhaps more precise recommendations might be suggested for diagnosis of MPS III, like testing urinary GAG levels (which is a quick and cheap assay) if any cognitive problems are observed in a child.…”

Section: Dovepressmentioning

confidence: 99%

“…[1][2][3][4] There are five subtypes of MPS III (A, B, C, D, and E), classified on the basis of the kind of mutated gene, and deficiency of specific enzyme (Table 1). [5][6][7] Four of these subtypes (A, B, C, and D) have been found in humans, while subtype E is currently known only from studies on an animal model, a mutant mice, constructed in the laboratory, with dysfunctional ARSG gene. [8][9][10] Therefore, although incompletely degraded HS is stored in each Sanfilippo disease subtype, every individual subtype is characterized by inhibition of decay of this GAG at specific stage of the process, being formally a separate metabolic disorder.…”

Section: Introduction -Brief Overview Of Sanfilippo Syndromementioning

confidence: 99%

“…All these diseases are inherited in an autosomal recessive manner, as residual activity of any enzyme involved in HS degradation at the level of 10-20% of the normal activity may ensure efficient decay process. [1][2][3][4][5][6][7] Because HS is present in virtually all tissues and organs, its storage affects majority of organs. Nevertheless, in Sanfilippo syndrome, symptoms occurring in visceral organs are milder than those in other types of MPS.…”

Section: Introduction -Brief Overview Of Sanfilippo Syndromementioning

confidence: 99%

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Sanfilippo Syndrome: Optimizing Care with a Multidisciplinary Approach

Cyske¹,

Anikiej-Wiczenbach²,

Wiśniewska³

et al. 2022

JMDH

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Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disease grouping five genetic disorders, four of them occurring in humans and one known to date only in a mouse model. In every subtype of MPS III (designed A, B, C, D or E), a lack or drastically decreased activity of an enzyme involved in the degradation of heparan sulfate (HS) (a compound from the group of glycosaminoglycans (GAGs)) arises from a genetic defect. This leads to primary accumulation of HS, and secondary storage of other compounds, combined with changes in expressions of hundreds of genes and many defects in organelles and various biochemical processes in the cell. As a result, dysfunctions of tissues and organs occur, leading to severe symptoms in patients. Although changes in somatic organs are considerable, the central nervous system is especially severely affected, and neurological, cognitive and behavioral disorders are the most significant changes, making the disease enormously burdensome for patients and their families. In the light of the current lack of any registered therapy for Sanfilippo syndrome (despite various attempts of many research groups to develop effective treatment, still no specific drug or procedure is available for MPS III), optimizing care with a multidisciplinary approach is crucial for managing this disease and making quality of patients' life passable. This includes efforts to make/organize (i) accurate diagnosis as early as possible (which is not easy due to various possible misdiagnosis events caused by similarity of MPS III symptoms to those of other diseases and variability of patients), (ii) optimized symptomatic treatment (which is challenging because of complexity of symptoms and often untypical responses of MPS III patients to various drugs), and (iii) psychological care (for both patients and family members and/or caregivers). In this review article, we focus on these approaches, summarizing and discussing them.

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Section: Importance Of Accurate Diagnosis and Diagnostic Problems In ...mentioning

confidence: 99%

Section: Dovepressmentioning

confidence: 99%

Section: Dovepressmentioning

confidence: 99%

Section: Introduction -Brief Overview Of Sanfilippo Syndromementioning

confidence: 99%

Section: Introduction -Brief Overview Of Sanfilippo Syndromementioning

confidence: 99%

See 3 more Smart Citations

Sanfilippo Syndrome: Optimizing Care with a Multidisciplinary Approach

Cyske¹,

Anikiej-Wiczenbach²,

Wiśniewska³

et al. 2022

JMDH

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Tubulin Cytoskeleton in Neurodegenerative Diseases–not Only Primary Tubulinopathies

et al. 2022

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Neurodegenerative diseases represent a large group of disorders characterized by gradual loss of neurons and functions of the central nervous systems. Their course is usually severe, leading to high morbidity and subsequent inability of patients to independent functioning. Vast majority of neurodegenerative diseases is currently untreatable, and only some symptomatic drugs are available which efficacy is usually very limited. To develop novel therapies for this group of diseases, it is crucial to understand their pathogenesis and to recognize factors which can influence the disease course. One of cellular structures which dysfunction appears to be relatively poorly understood in the light of neurodegenerative diseases is tubulin cytoskeleton. On the other hand, its changes, both structural and functional, can considerably influence cell physiology, leading to pathological processes occurring also in neurons. In this review, we summarize and discuss dysfunctions of tubulin cytoskeleton in various neurodegenerative diseases different than primary tubulinopathies (caused by mutations in genes encoding the components of the tubulin cytoskeleton), especially Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, prion diseases, and neuronopathic mucopolysaccharidoses. It is also proposed that correction of these disorders might attenuate the progress of specific diseases, thus, finding newly recognized molecular targets for potential drugs might become possible.

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Dysregulation of genes coding for proteins involved in metabolic processes in mucopolysaccharidoses, evidenced by a transcriptomic approach

Pierzynowska,

Deresz,

Węgrzyn

et al. 2023

Metab Brain Dis

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Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSD) caused by mutations in genes coding for enzymes responsible for degradation of glycosaminoglycans (GAGs). Most types of these severe disorders are characterized by neuronopathic phenotypes. Although lysosomal accumulation of GAGs is the primary metabolic defect in MPS, secondary alterations in biochemical processes are considerable and influence the course of the disease. Early hypothesis suggested that these secondary changes might be due to lysosomal storage-mediated impairment of activities of other enzymes, and subsequent accumulation of various compounds in cells. However, recent studies indicated that expression of hundreds of genes is changed in MPS cells. Therefore, we asked whether metabolic effects observed in MPS are caused primarily by GAG-mediated inhibition of specific biochemical reactions or appear as results of dysregulation of expression of genes coding for proteins involved in metabolic processes. Transcriptomic analyses of 11 types of MPS (using RNA isolated from patient-derived fibroblasts), performed in this study, showed that a battery of the above mentioned genes is dysregulated in MPS cells. Some biochemical pathways might be especially affected by changes in expression of many genes, including GAG metabolism and sphingolipid metabolism which is especially interesting as secondary accumulation of various sphingolipids is one of the best known additional (while significantly enhancing neuropathological effects) metabolic defects in MPS. We conclude that severe metabolic disturbances, observed in MPS cells, can partially arise from changes in the expression of many genes coding for proteins involved in metabolic processes.

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Misdiagnosis in mucopolysaccharidoses

Cited by 19 publications

References 99 publications

Sanfilippo Syndrome: Optimizing Care with a Multidisciplinary Approach

Sanfilippo Syndrome: Optimizing Care with a Multidisciplinary Approach

Tubulin Cytoskeleton in Neurodegenerative Diseases–not Only Primary Tubulinopathies

Dysregulation of genes coding for proteins involved in metabolic processes in mucopolysaccharidoses, evidenced by a transcriptomic approach

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