B-cell-specific accumulation of inclusion bodies loaded with HLA class II molecules in patients with mucolipidosis II (I-cell disease)

Yokoi, Ayano; Niida, Yo; Kuroda, Masashi; Imi-Hashida, Yoko; Toma, Tomoko; Yachie, Akihiro

doi:10.1038/s41390-018-0234-2

Cited by 2 publications

(4 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2007, Kawashima et al reported inclusion bodies in the lysosomes of ML II patient fibroblasts that included GM2 ganglioside, oligosaccharides, and various kinds of glycoconjugates having sialic acidα2-3galactose, galactoseβ1-4N-acetylglucosamine, and mannose residues [ 76 ]. In 2019, Yokoi et al reported inclusion bodies in the B cells of three unrelated ML II patients, which had an accumulation of HLA class II molecules [ 77 ]. In contrast, CD4+ T cells, CD8+ T cells, natural killer cells, monocytes, or neutrophils did not contain the inclusions.…”

Section: Diagnosis Of ML Ii/iii Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Mucolipidoses Overview: Past, Present, and Future

Khan

Tomatsu

2020

IJMS

View full text Add to dashboard Cite

Mucolipidosis II and III (ML II/III) are caused by a deficiency of uridine-diphosphate N-acetylglucosamine: lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. The process is performed by a sequential two-step process: first, GlcNAc-1-phosphotransferase catalyzes the transfer of GlcNAc-1-phosphate to the selected mannose residues on lysosomal enzymes in the cis-Golgi network. The second step removes GlcNAc from lysosomal enzymes by N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (uncovering enzyme) and exposes the mannose 6-phosphate (M6P) residues in the trans-Golgi network, in which the enzymes are targeted to the lysosomes by M6Preceptors. A deficiency of GlcNAc-1-phosphotransferase causes the hypersecretion of lysosomal enzymes out of cells, resulting in a shortage of multiple lysosomal enzymes within lysosomes. Due to a lack of GlcNAc-1-phosphotransferase, the accumulation of cholesterol, phospholipids, glycosaminoglycans (GAGs), and other undegraded substrates occurs in the lysosomes. Clinically, ML II and ML III exhibit quite similar manifestations to mucopolysaccharidoses (MPSs), including specific skeletal deformities known as dysostosis multiplex and gingival hyperplasia. The life expectancy is less than 10 years in the severe type, and there is no definitive treatment for this disease. In this review, we have described the updated diagnosis and therapy on ML II/III.

show abstract

Section: Diagnosis Of ML Ii/iii Patientsmentioning

confidence: 99%

“…These results suggest a potential role for N -acetylglucosamine-1-phosphotransferase in immune functions. Furthermore, the fact that only B cells contain the inclusions provides a novel diagnostic aid for the diagnosis of I-cell disease [ 77 ]. Lymphocytes include T cells, B cells, and NK cells.…”

Section: Diagnosis Of ML Ii/iii Patientsmentioning

confidence: 99%

Mucolipidoses Overview: Past, Present, and Future

Khan

Tomatsu

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Subsequently, newly synthesized lysosomal enzymes are secreted into the extracellular space rather than targeted to the lysosomes. Thus, affected lysosomes are secondarily deficient in most acid hydrolases; undigested junk materials accumulate within the lysosomes [ 1 , 2 ]. ML II was first described as inclusion-cell (I-cell) disease by Leroy and Demars in 1967 [ 3 ], because the fibroblasts derived from patients contain abundant ‘inclusions’ (now recognized as swollen lysosomes) within the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

“…ML II was first described as inclusion-cell (I-cell) disease by Leroy and Demars in 1967 [ 3 ], because the fibroblasts derived from patients contain abundant ‘inclusions’ (now recognized as swollen lysosomes) within the cytoplasm. These inclusions are observed not only in cultured skin fibroblasts, but also in a variety of other cell types in vivo, including peripheral blood lymphocytes [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Secondary Hyperparathyroidism in Children with Mucolipidosis Type II (I-Cell Disease): Irish Experience

Boruah

Monavari

Conlon

et al. 2022

JCM

View full text Add to dashboard Cite

Mucolipidosis type II (ML II) is an autosomal recessive lysosomal targeting disorder that may present with features of hyperparathyroidism. The aim of this study was to describe in detail the clinical cases of ML II presenting to a tertiary referral centre with biochemical and/or radiological features of hyperparathyroidism. There were twenty-three children diagnosed with ML II in the Republic of Ireland from July 1998 to July 2021 inclusive (a 23-year period). The approximate incidence of ML II in the Republic of Ireland is, therefore, 1 per 64,000 live births. Medical records were available and were reviewed for 21 of the 23 children. Five of these had been identified as having biochemical and/or radiological features of hyperparathyroidism. Of these five, three children were born to Irish Traveller parents and two to non-Traveller Irish parents. All five children had radiological features of hyperparathyroidism (on skeletal survey), with evidence of antenatal fractures in three cases and an acute fracture in one. Four children had biochemical features of secondary hyperparathyroidism. Three children received treatment with high dose Vitamin D supplements and two who had antenatal/acute fractures were managed with minimal handling. We observed resolution of secondary hyperparathyroidism in all cases irrespective of treatment. Four of five children with ML II and hyperparathyroidism died as a result of cardiorespiratory failure at ages ranging from 10 months to 7 years. Biochemical and/or radiological evidence of hyperparathyroidism is commonly identified at presentation of ML II. Further studies are needed to establish the pathophysiology and optimal management of hyperparathyroidism in this cohort. Recognition of this association may improve diagnostic accuracy and management, facilitate family counseling and is also important for natural history data.

show abstract

B-cell-specific accumulation of inclusion bodies loaded with HLA class II molecules in patients with mucolipidosis II (I-cell disease)

Cited by 2 publications

References 26 publications

Mucolipidoses Overview: Past, Present, and Future

Mucolipidoses Overview: Past, Present, and Future

Secondary Hyperparathyroidism in Children with Mucolipidosis Type II (I-Cell Disease): Irish Experience

Contact Info

Product

Resources

About