The I-Cell model: the molecular basis for abnormal lysosomal enzyme transport in mucolipidosis II and mucolipidosis III

Sly, William S.; Sundaram, Vasantha

doi:10.1016/b978-0-407-02312-3.50010-7

Cited by 2 publications

(2 citation statements)

References 80 publications

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“…These are characterised by disordered processing of multiple lysosomal degradative enzymes caused by the deficiency or abnormal function of UDP‐ N ‐acetylglucosamine : lysosomal enzyme N ‐acetylglucosaminyl‐1‐phosphotransferase, commonly termed UDP‐GlcNAc 1‐phosphotransferase (GlcNAc‐PT) 2,3 . The underlying defects result in deficient post‐translational modification of numerous enzymes, which depend on mannose phosphorylation for uptake and localisation by cells where substrate degradation occurs 4 . This in turn results in effective deficiencies of lysosomal degradative enzymes with concomitant intracellular accumulation of both partly degraded glycosaminoglycans and sphingolipids.…”

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confidence: 99%

The natural history and osteodystrophy of mucolipidosis types II and III

David-Vizcarra¹,

Briody

Ault

et al. 2010

J Paediatrics Child Health

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Aim To assess the natural history and impact of the secondary bone disease observed in patients with Mucolipidosis II and III. Methods Affected children and adults were ascertained from clinical genetics units around Australia and New Zealand and the National Lysosomal Diseases Research Unit in Adelaide. The study encompassed all patients ascertained between 1975 and 2005. Data focussing on biochemical parameters at diagnosis, and longitudinal radiographic findings were sought for each patient. Where feasible, patients underwent clinical review and examination. Examinations included skeletal survey, bone densitometry, and measurement of serum and urine markers of bone metabolism. Functional assessment was performed using the Pediatric Evaluation and Disability Inventory (PEDI). Results 25 patients with ML II and III were ascertained over a 30-year period. Serum calcium (median 2.35 mmol/L range 2.16–2.64) and phosphate (median 1.51 mmol/L range 1.17–1.72) were normal but five patients had mild elevation of alkaline phosphatase. Serum osteocalcin and urine deoxypyridinoline/creatinine were elevated. Two radiological patterns were observed (i) transient neonatal hyperparathyroidism in infants with ML II and (ii) progressive osteodystrophy in patients with ML II/III and ML III. Molecular Genetic analysis of mutations in the αβsubunit of the UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosaminyl-1-phosphotransferase gene in 9 subjects correlated with the phenotypic severity. Conclusion ML is characterised by a progressive bone and mineral disorder which we describe as the Osteodystrophy of Mucolipidosis. The clinical and radiographic features of this osteodystrophy are consistent with a syndrome of “Pseudohyperparathyroidism”. Much of the progressive skeletal and joint pathology is attributable to this bone disorder.

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confidence: 99%

The natural history and osteodystrophy of mucolipidosis types II and III

David-Vizcarra¹,

Briody

Ault

et al. 2010

J Paediatrics Child Health

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“…ML II is a progressive multi-organ disease, usually with prenatal clinical onset and fatal outcome within the first decade of life due to cardiopulmonary complications [ 5 ]. It is characterized by coarse facial features, short stature, hyperplastic gums, organomegaly, retarded psychomotor development and skeletal deformities, which may include shortened limbs, flexion contractures and talipes [ 6 , 7 ]. Secondary hyperparathyroidism is a recognized feature of ML II [ 1 , 7 , 8 , 9 , 10 , 11 ].…”

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confidence: 99%

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

Boruah

Monavari

Conlon

et al. 2022

JCM

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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.

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The I-Cell model: the molecular basis for abnormal lysosomal enzyme transport in mucolipidosis II and mucolipidosis III

Cited by 2 publications

References 80 publications

The natural history and osteodystrophy of mucolipidosis types II and III

The natural history and osteodystrophy of mucolipidosis types II and III

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

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