Mucolipidoses Overview: Past, Present, and Future

Khan, Shaukat; Tomatsu, Saori C

doi:10.3390/ijms21186812

Cited by 28 publications

(24 citation statements)

References 117 publications

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“…Also, Khan and Tomatsu stated that these disorders share characteristic bone deformities. In addition, several lysosomal glycosidases and sulfatases enzymes are deficient in ML lysosomes and are involved in a step by step degradation of GAGs [ 48 ]. During the study period, 47 mucolipidosis cases were diagnosed.…”

Section: Discussionmentioning

confidence: 99%

Mucopolysaccharidoses diagnosis in the era of enzyme replacement therapy in Egypt

Fateen

Abdallah

Nazim

et al. 2021

Heliyon

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Background Undegraded glycosaminoglycans (GAGs) induced by deficiency of enzymes are the primary cause of mucopolyscchardoses. Mucopolysacchardoses (MPS) are a group of rare lysosomal storage diseases (LSD). The quantification of a specific enzymatic activity is needed for accurate diagnosis. The objectives of this work were: first, to continue the study of mucopolysacchardoses disease in Egypt after the start of using the enzyme replacement therapy (ERT). Second, to define the commonest types among our population after 18 years experience with the disease. Third, to compare the different MPS types’ distribution, diagnosed after the start of the ERT, to identify the impact of using ERT on the number and type of diagnosed patients. Method Urinary GAGs were measured for all referred cases followed by two-dimensional electrophoretic separation for cases with high levels of GAGs; the specific enzyme activity was assayed for each type depending on the abnormal electrophoretic pattern obtained. Clinically suspected cases of Morquio syndrome were directly subjected to measuring the specific enzyme. Results Out of 1448 suspected cases, 622 (42.9%) MPS patients were diagnosed revealing the following distribution: MPS I (172, 27.7%), MPS II (57, 9.1%), MPS III [(177, 28.5%: 134 type B and 43 types A, C or D)], MPS IVA (124, 19.9%), MPS VI (90, 14.5%) and MPS VII (2, 0.3%). MPS III was the most commonly diagnosed type followed by MPS I and MPS IVA. MPS IVA represented the most common type receiving treatment, followed by MPS I, MPS II and MPS VI. Conclusion The presence of treatment encouraged the affected families and physicians to seek diagnosis. MPS III was the commonest type among our studied group after 7 years of diagnosis, while MPS IVA was the commonest type receiving treatment.

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Section: Discussionmentioning

confidence: 99%

Mucopolysaccharidoses diagnosis in the era of enzyme replacement therapy in Egypt

Fateen

Abdallah

Nazim

et al. 2021

Heliyon

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“…In MLII and III, an absent or reduced GlcNAc-1-phosphotransferase activity results in global mis-sorting of lysosomal enzymes and subsequent secretion into the extracellular compartment. Consecutively, partially degraded macromolecules (i.e., glycosaminoglycans, phospholipids, cholesterol) accumulate in the lysosomes impairing cellular function [4].…”

Section: Introductionmentioning

confidence: 99%

“…The estimated incidence of MLII and III globally ranges from 0.22 to 2.70 per 100,000 live births [5]. No curative therapy is yet available [4].…”

Section: Introductionmentioning

confidence: 99%

“…The overlapping progressive symptoms comprise craniofacial dysmorphism (i.e., flat face, shallow orbits, depressed nasal bridge, macroglossia), a short neck, respiratory insufficiency and upper airway obstruction, sleep apnoea, cardiac dysfunction, skeletal deformities (e.g., growth impairment, spine and chest deformity), and neurocognitive delay. Radiological features are subsumed as dysostosis multiplex [4][5][6]8,9]. For patients with MPS, these symptoms are known to be associated with a high risk of morbidity and mortality when undergoing general anaesthesia [10].…”

Section: Introductionmentioning

confidence: 99%

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Anaesthesia-Relevant Disease Manifestations and Perianaesthetic Complications in Patients with Mucolipidosis—A Retrospective Analysis of 44 Anaesthetic Cases in 12 Patients

Ammer

Muschol

Santer

et al. 2022

JCM

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Mucolipidosis (ML) type II, intermediate, and III are lysosomal storage disorders with progressive multiorgan manifestations predisposing patients to a high risk of perioperative morbidity. The aims of the study were to systematically assess disease manifestations relevant to anaesthesia as well as anaesthesia-related complications. This retrospective study includes ML patients who underwent anaesthesia in two centres between 2008 and 2022. We reviewed patients’ demographics, medical history, disease manifestations, as well as procedure- and outcome-related data. A total of 12 patients (7 MLII, 2 ML intermediate, 3 MLIII) underwent 44 anaesthesia procedures (per patient: median 3, range 1–11). The median age was 3.3 years (range 0.1–19.1). At least one complication occurred in 27.3% of the anaesthesia procedures. The vast majority of complications (94%) occurred in children with MLII and ML intermediate. A predicted difficult airway was found in 100% and 80% of the MLII and ML intermediate patients, respectively. Accordingly, most complications (59%) occurred during the induction of anaesthesia. Altogether, respiratory complications were the most frequent (18%), followed by difficult airway management (14%). The risk for anaesthesia-related complications is alarmingly high in patients with ML, particularly in those with MLII and ML intermediate. Multidisciplinary risk–benefit analysis and thoughtful anaesthesia planning are crucial in these patients.

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“…Disruption of M6P biogenesis or its sorting results in the mistargeting of most lysosomal enzymes 8 . Mutations in GNPT cause two distinct lysosome storage diseases (LSDs) 8,9 .…”

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confidence: 99%

GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway

Zhang

Yang

et al. 2022

Nat Commun

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The mannose-6-phosphate (M6P) biosynthetic pathway for lysosome biogenesis has been studied for decades and is considered a well-understood topic. However, whether this pathway is regulated remains an open question. In a genome-wide CRISPR/Cas9 knockout screen, we discover TMEM251 as the first regulator of the M6P modification. Deleting TMEM251 causes mistargeting of most lysosomal enzymes due to their loss of M6P modification and accumulation of numerous undigested materials. We further demonstrate that TMEM251 localizes to the Golgi and is required for the cleavage and activity of GNPT, the enzyme that catalyzes M6P modification. In zebrafish, TMEM251 deletion leads to severe developmental defects including heart edema and skeletal dysplasia, which phenocopies Mucolipidosis Type II. Our discovery provides a mechanism for the newly discovered human disease caused by TMEM251 mutations. We name TMEM251 as GNPTAB cleavage and activity factor (GCAF) and its related disease as Mucolipidosis Type V.

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Mucolipidoses Overview: Past, Present, and Future

Cited by 28 publications

References 117 publications

Mucopolysaccharidoses diagnosis in the era of enzyme replacement therapy in Egypt

Mucopolysaccharidoses diagnosis in the era of enzyme replacement therapy in Egypt

Anaesthesia-Relevant Disease Manifestations and Perianaesthetic Complications in Patients with Mucolipidosis—A Retrospective Analysis of 44 Anaesthetic Cases in 12 Patients

GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway

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