Abstract
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.
Highlights
Mucolipidosis type II (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’ within the cytoplasm
The diagnosis of ML II was based on clinical features and biochemical testing by detecting increased activity of alpha mannosidase and beta hexosaminidase in plasma
All five patients had been tested for hyperparathyroidism within the first few weeks of life and four had increased levels of parathyroid hormone (PTH)
Summary
Mucolipidosis type II (ML II) (OMIM #252500) or inclusion cell disease (I-cell disease) is a rare autosomal recessive lysosomal enzymetargeting disease due to deficiency of uridine diphosphate-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1phosphotransferase (GlcNac-1-phosphotransferase). This enzyme is involved in the first step of the mannose 6-phosphate signal, which allows specific targeting of lysosomal acid hydrolase from the trans-Golgi network to lysosomes. 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’ ( recognized as swollen lysosomes) within the cytoplasm. These inclusions are observed in cultured skin fibroblasts, and in a variety of other cell types in vivo, including peripheral blood lymphocytes [2]
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