22 research outputs found
Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls
Mucopolysaccharidosis II (MPS II), or Hunter syndrome, is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Affected patients suffer progressive damage to multiple organ systems and early mortality. Two thirds of patients also manifest cognitive impairment and developmental delays. MPS II can be extremely difficult to diagnose before irreversible organ and tissue damage has occurred because of an insidious onset and the overlap in signs and symptoms with common childhood complaints. This is particularly true of patients without cognitive impairment (attenuated phenotype). Although not curative, early treatment with enzyme replacement therapy before irreversible organ damage has occurred may result in the greatest clinical benefit. Here, the signs, symptoms, and surgical history that should trigger suspicion of MPS II are described, and the diagnostic process is reviewed with a focus on practical considerations and the avoidance of common diagnostic pitfalls. Once a diagnosis is made, multidisciplinary management with an extended team of pediatric specialists is essential and should involve the pediatrician or family practice physician as facilitator and medical home for the patient and family. Conclusion: Because routine newborn screening is not yet available for MPS II, the involvement and awareness of pediatricians, family practice physicians, and pediatric specialists is critical for early identification, diagnosis, and referral in order to help optimize patient outcomes
Neurologic Abnormalities in Mouse Models of the Lysosomal Storage Disorders Mucolipidosis II and Mucolipidosis III Îł
Mutation Analysis of 16 Mucolipidosis II and III Alpha/Beta Chinese Children Revealed Genotype-Phenotype Correlations
Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype–phenotype correlation
Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes
N-acetylglucosamine-1-phosphate transferase, alpha/beta and gamma subunits; N-acetylglucosamine-1- (GNPTAB, GNPTG)
GlcNAc-1-phosphotransferase catalyzes the transfer of a GlcNAc-1-phosphate
residue from UDP-GlcNAc to C6 positions of selected mannoses in highmannose-
type oligosaccharides of the hydrolases (Goldberg and Kornfeld
1981; Natowicz et al. 1982; Varki and Kornfeld 1983). At a biological level
this reaction is followed by the removal of the terminal GlcNAc by an
N-acetylglucosamine-1-phosphodiester α-N-acetyl-glucosaminidase, usually
referred to as “uncovering enzyme” (UCE; see Chap. 78; Article ID: 332135).
Sequential action of these two enzymes results in the formation of the
mannose-6-phosphate (Man-6-P) marker, a specific tag acquired by lysosomal
hydrolases that ensures recognition by M6P receptors and delivery to the
endosomal/lysosomal system (Braulke and Bonifacino 2009)
Vacuolization of mucolipidosis type II mouse exocrine gland cells represents accumulation of autolysosomes
Mucolipidosis II mice, as well as patients with this disorder, exhibit extensive vacuolization of their exocrine gland cells. We now demonstrate that the vacuoles are enlarged autolysosomes containing undigested cytoplasmic material that accumulate secondary
to deficient lysosomal degradative function. A model to explain this finding is proposed