Pitfalls in the prenatal diagnosis of mucolipidosis II alpha/beta: A case report

Alegra, Taciane; Koppe, Tiago; Acosta, Angelina Xavier; Sarno, Manoel; Burin, Maira Graeff; Kessler, Rejane Gus; Sperb‐Ludwig, Fernanda; Cury, Gabriela Kampf; Baldo, Guilherme; Matte, Úrsula da Silveira; Giugliani, Roberto; Schwartz, Ida Vanessa Döederlein

doi:10.1016/j.mgene.2014.03.003

Cited by 7 publications

(9 citation statements)

References 13 publications

(12 reference statements)

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“…19 We described the difficulties found in the prenatal diagnosis of a heterozygous individual, the brother of a patient in our cohort. 20 In one of the patients, with very mild phenotype suggesting ML III, the diagnosis was just Fig. 3 (A-C) ML type III gamma (41-year-old patient), joint contractures, elbows, shoulders, and hands; this patient has bilateral hip prosthesis.…”

Section: Discussionmentioning

confidence: 97%

Clinical Characterization of Mucolipidoses II and III: A Multicenter Study

et al. 2019

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Mucolipidoses (MLs) II and III are rare lysosomal diseases caused by deficiency of GlcNAc-1-phosphotransferase, and clinical manifestations are multisystemic. Clinical and demographic data from 1983 to 2013 were obtained retrospectively. Twenty-seven patients were included (ML II = 15, ML III α/beta = 9, ML III gamma = 3). The median age at diagnosis was 2.7 years. The predominant clinical presentations were skeletal symptoms. The ML II patients showed physical and cognitive impairment, while the ML III α/beta patients have more somatic abnormalities and usually were delayed in early development as compared with ML III gamma patients. This is the most comprehensive study exploring characteristics of Brazilian patients with MLs II and III.

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Section: Discussionmentioning

confidence: 97%

Clinical Characterization of Mucolipidoses II and III: A Multicenter Study

et al. 2019

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“…Skeletal radiographs reveal signs of dysostosis multiplex and chondrodysplasia. Prenatal manifestations can include bone dysplasia with shortened and curved bones and/or bone fractures (Aggarwal et al, ; Alegra et al, ; Costain et al, ; Heo et al, ; Yang et al, ; Yuksel, Kayserili, & Gungor, ). Patients present with a progressive psychomotor retardation.…”

Section: Diagnosis Of MLII Mliii Alpha/beta and Mliii Gammamentioning

confidence: 99%

“…The clinical diagnosis of MLII or MLIII can be confirmed by biochemical analysis of patient's material. Defects in GlcNAc‐1‐phosphotransferase result in missorting of lysosomal enzymes (Figure b), which can be easily detected by measurement of lysosomal enzyme activities in plasma, dried blood, and media from cultured fibroblasts or amniocytes (Alegra et al, ; Pohl et al, ; Sperb‐Ludwig et al, ; Steet et al, ; Tiede et al, ; Tiede, Storch, et al, ; Velho et al, ). Thereby, a 5‐ to 20‐fold increase in lysosomal enzyme activities is considered to be pathogenic.…”

Section: Diagnosis Of MLII Mliii Alpha/beta and Mliii Gammamentioning

confidence: 99%

The lysosomal storage disorders mucolipidosis type II, type III alpha/beta, and type III gamma: Update onGNPTABandGNPTGmutations

et al. 2019

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Mutations in the GNPTAB and GNPTG genes cause mucolipidosis (ML) type II, type III alpha/beta, and type III gamma, which are autosomal recessively inherited lysosomal storage disorders. GNPTAB and GNPTG encode the α/β‐precursor and the γ‐subunit of N‐acetylglucosamine (GlcNAc)‐1‐phosphotransferase, respectively, the key enzyme for the generation of mannose 6‐phosphate targeting signals on lysosomal enzymes. Defective GlcNAc‐1‐phosphotransferase results in missorting of lysosomal enzymes and accumulation of non‐degradable macromolecules in lysosomes, strongly impairing cellular function. MLII‐affected patients have coarse facial features, cessation of statural growth and neuromotor development, severe skeletal abnormalities, organomegaly, and cardiorespiratory insufficiency leading to death in early childhood. MLIII alpha/beta and MLIII gamma are attenuated forms of the disease. Since the identification of the GNPTAB and GNPTG genes, 564 individuals affected by MLII or MLIII have been described in the literature. In this report, we provide an overview on 258 and 50 mutations in GNPTAB and GNPTG, respectively, including 58 novel GNPTAB and seven novel GNPTG variants. Comprehensive functional studies of GNPTAB missense mutations did not only gain insights into the composition and function of the GlcNAc‐1‐phosphotransferase, but also helped to define genotype‐phenotype correlations to predict the clinical outcome in patients.

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“…To the best of our knowledge, only one case has been published on the prenatal diagnosis of ML II/III by means of molecular study [8]. In Korea, a prenatal test of ML II/III is legal, and this is the first case of prenatal investigation of ML II/III.…”

Section: Discussionmentioning

confidence: 99%

“…Of these, a mutation study of GNPTAB is important in terms of confirmation of disease and prediction of prognosis. In addition, a molecular analysis of GNPTAB is essential for prenatal diagnosis of ML II/III [8]. In the present study, we investigated GNPTAB mutations in five patients with ML II/III and successfully performed prenatal testing in two pregnant women.…”

Section: Introductionmentioning

confidence: 99%

Clinical, biochemical and molecular characterization of Korean patients with mucolipidosis II/III and successful prenatal diagnosis

Yang

Cho

Park

et al. 2017

Orphanet J Rare Dis

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Background: Mucolipidosis types II and III (ML II/III) are autosomal recessive disorders caused by a deficiency in the lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. We investigated the molecular genetic characteristics of the GNPTAB gene, which codes for the alpha/beta subunits of a phosphotransferase, in Korean ML II/III patients. We included prenatal tests and evaluated the spectrum of mutations in East Asian populations with ML II/III through a literature review. Methods: Seven patients from six families were enrolled in the study including two prenatal tests using chorionic villi samples. A diagnosis of ML II/III was made based on clinical findings and increases in serum lysosomal enzyme levels. PCR and direct sequencing were performed to identify GNPTAB mutations.

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Pitfalls in the prenatal diagnosis of mucolipidosis II alpha/beta: A case report

Cited by 7 publications

References 13 publications

Clinical Characterization of Mucolipidoses II and III: A Multicenter Study

Clinical Characterization of Mucolipidoses II and III: A Multicenter Study

The lysosomal storage disorders mucolipidosis type II, type III alpha/beta, and type III gamma: Update onGNPTABandGNPTGmutations

Clinical, biochemical and molecular characterization of Korean patients with mucolipidosis II/III and successful prenatal diagnosis

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