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Mucolipidosis II and III/ (I-cell disease and pseudo-Hurler polydystrophy) N-acetyl-glucosaminyl-l-phosphotransferase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Mucolipidosis II and III reflect multiple deficiencies of many lysosomal hydrolases that require post-translational processing to form the recognition site that permits their cellular uptake. The fundamental defect is in N-acetylglucosaminyl-l-phosphotransferase (GlcNAc phosphotransferase) (Figure 83.2) [1]. The lysosomal enzyme substrates for this enzyme are glycoproteins containing reactive mannose molecules, and in the reaction a GlcNAc phosphate is linked to the mannose; a subsequent phosphodiesterase reaction cleaves off the GlcNAc, leaving the mannose phosphate recognition site. Patients with I-cell disease, or mucolipidosis II, have complete deficiency of this enzyme, while patients with mucolipidosis III have varying amounts of residual activity of the enzyme. Variable patterns of clinical phenotype in mucolipidosis III reflect the considerable variation in enzyme activity as well as its effect on so very many lysosomal enzymes. The extent of the phenotypic variability has doubtless not yet been defined. Leroy and colleagues [2, 3] gave the disease its name I-cell disease, the I indicating inclusions.
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Differential diagnosis: stippling may be a feature of many disorders, which include chondrodysplasia punctata (p. 272); warfarin embryopathy (p. 294); fetal exposure to hydantoin and alcohol; trisomy 18 (p. 586); trisomy 21. CHILD syndrome: an acronym for Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects, a very rare condition which shows unilateral involvement with joint contractures, limb hypoplasia and a wide range of organ malformations (cardiac, genitourinary, endocrine, cerebral); Zellweger syndrome (p. 301); mucolipidosis type 2 (I-cell disease) (p. 381); GM gangliosidosis type 1 – findings are similar to I-cell disease and it is also a storage disorder; Cornelia de Lange syndrome (p. 454); Sjogren syndrome; multiple sulphatase deficiency, a recessive condition caused by mutations in the sulphatase-modifying factor-1 gene (SUMF1), responsible for the activation of all the sulphatase enzymes in the cell. Smith-Lemli-Opitz syndrome – caused by a defect in the enzyme 3 beta-hydroxysterol-delta 7-reductase; this converts 7-dehydrocholesterol to cholesterol (gene DHCR7). This more complex syndrome has characteristic facial traits (bitemporal narrowing, ptosis, broad nasal bridge, short nasal root, anteverted nares, micrognathia), cleft palate, brain anomalies (microcephaly, agenesis of the corpus callo-sum, holoprosencephaly), and anomalies of genital, cardiovascular and gastrointestinal systems. Skeletal anomalies include rhizomelia, postaxial polydactyly, syndactyly of second and third toes and short, proximally placed thumbs.
Current and emerging pharmacotherapy for Gaucher disease in pediatric populations
Published in Expert Opinion on Pharmacotherapy, 2021
Richard Sam, Emory Ryan, Emily Daykin, Ellen Sidransky
In 1964, Christian de Duve first suggested that lysosomal storage diseases might be treated by enzyme replacement. Dr. Roscoe O. Brady, having discovered that deficient GCase led to the development of GD, first proposed a strategy to replace the missing enzyme by supplementing deficient enzyme [70,71]. The proof-of-concept of ERT was initially established in vitro in the monogenic disorder I-cell disease [72]. However, implementing ERTs for patients with GD1 required the production of purified, concentrated enzyme from human origins. Over three decades, the development of ERTs focused on assessing the efficacy of placenta-derived GCase, alglucerase, and then finally recombinant GCase, or imiglucerase. The recombinant protein, generated using Chinese hamster ovary (CHO) cells in the mid-1990s, continues to serve as the most widely used GCase in clinics globally. Several other forms of the recombinant enzyme, including taliglucerase and velaglucerase alpha, which are produced in plant cells and human fibrosarcoma lines, respectively, subsequently received approval and are used to treat GD [73,74] (Table 2). The enzyme preparations are all administered intravenously. Some patients receive infusions at clinics, hospitals, or at home through either self-administration or administration by visiting nurses.
Prevalence of colour vision deficiency in the Republic of Ireland schoolchildren and associated socio-demographic factors
Published in Clinical and Experimental Optometry, 2021
Síofra Harrington, Peter A Davison, Veronica O'dwyer
There is a higher prevalence of recessive diseases,21 such as galactosaemia, Hurlers syndrome and I‐cell disease in the Irish Traveller community, due to social isolation and consanguineous marriages.21 As per the 2016 Irish census, 1.5 per cent of 5–14‐year‐old children were Traveller; however, the de facto number is likely to be larger; Irish Travellers are White Irish, yet, as per the 2016 Irish census, one had to declare as White Irish or Irish Traveller. Furthermore, there is evidence of greater undercoverage of the Traveller population in the Irish census when compared to the settled community.22