Child Neurology: Exaggerated dermal melanocytosis in a hypotonic infant

Armstrong‐Javors, Amy; Chu, Catherine J.

doi:10.1212/wnl.0000000000000912

Cited by 12 publications

(4 citation statements)

References 10 publications

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“…[ 3 ] Death occurs by 3–4 years of age, most commonly from aspiration pneumonia or cardiac problems. [ 4 ]…”

Section: Discussionmentioning

confidence: 99%

“…There are 54 reported cases of extensive Mongolian spots with various IEM, in which 25 cases are associated with Hurler syndrome, 17 with GM1 gangliosidosis, 9 with Hunter syndrome, 2 with α-mannosidosis, and 1 with Niemann–Pick disease. [ 4 ] Of these 25 cases of Hurler syndrome, 19 have been reported in a single study by Gonzalez et al . [ 8 ] However, in recent years, reporting of extensive Mongolian spots with GM1 gangliosidosis is more frequent in comparison to Hurler syndrome.…”

Section: Discussionmentioning

confidence: 99%

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Extensive Mongolian spots in a hypotonic infant with GM1 gangliosidosis

Ranjan

Patra

2018

J Pediatr Neurosci

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“…[ 3 ] Death occurs by 3–4 years of age, most commonly from aspiration pneumonia or cardiac problems. [ 4 ]…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Extensive Mongolian spots in a hypotonic infant with GM1 gangliosidosis

Ranjan

Patra

2018

J Pediatr Neurosci

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“…GM1 gangliosidosis is an autosomal recessive storage disorder, which occurs in 1 per 100,000 to 200,000 newborns [1]. It is caused by a deficiency of beta-galactosidase (GLB1), a lysosomal hydrolase that may be defective with respect to keratan sulfate in Morquio B disease (MBD) or to gangliosides, lactosylceramide, asialofetuin, and oligosaccharides carrying terminal beta-linked galactose and keratan sulfate in GM1-gangliosidosis [2].…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis of Undiagnosed Juvenile GM1-Gangliosidosis by Microarray and Exome Sequencing

Bouhouche

Tibar

Kriouale

et al. 2018

Case Reports in Genetics

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GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder due to mutations in the lysosomal acid 3-galactosidase gene, GLB1. It is usually classified into three forms, infantile, juvenile, or adult, based on age at onset and severity of central nervous system involvement. Because of their broad clinical spectrum and their similarity to many other aetiologies, including inherited neurodegenerative and metabolic diseases, it is often difficult to diagnose such diseases. Recently, whole exome sequencing (WES) has become increasingly used when a strong hypothesis cannot be formulated based on the clinical phenotype. Here, we present three patients belonging to a consanguineous Moroccan family with a GM1-gangliosidosis with unusual clinical onset and atypical radiological presentation that had eluded diagnosis for over a decade. To identify the disease-causing mutation, we performed a whole exome sequencing and a chromosomal microarray genotyping in order to reduce the number of genetic variants to be interpreted, by focusing the data analysis only on the linked loci. The already known pathogenic missense mutation c.601G>A in GLB1 (p.R201C) was found at homozygous state in the proband V.1 and at heterozygous state in his father IV.1. The mutation was validated by Sanger sequencing and segregated in all the family members according to a recessive mode of inheritance. Outside of the linked loci, we found the EXOSC8 p.Ser272Thr mutation at heterozygous state in all the patients and their mother IV.2. This mutation was reported to cause pontocerebellar hypoplasia type 1C and could act as a modifying factor that exacerbates the brain atrophy of patients. Our study identified the first GLB1 mutation in North Africa in patients with unexpected brain-MRI outcomes extending the clinical spectrum of the GM1-gangliosidosis.

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“…The inflammation seems to play an important role in pathogenesis of the disease and its neurological manifestations [ 4 ]. GM1 gangliosidosis is estimated to occur in 1 per 100,000 to 200,000 newborns [ 5 ]. Until now, different types of GM1-gangliosidosis have been described.…”

Section: Introductionmentioning

confidence: 99%

Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene

et al. 2017

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BackgroundType II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3–4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types.Case presentationHere, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from “Lurs” ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance.ConclusionsOur study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients.

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Child Neurology: Exaggerated dermal melanocytosis in a hypotonic infant

Cited by 12 publications

References 10 publications

Extensive Mongolian spots in a hypotonic infant with GM1 gangliosidosis

Extensive Mongolian spots in a hypotonic infant with GM1 gangliosidosis

Genetic Analysis of Undiagnosed Juvenile GM1-Gangliosidosis by Microarray and Exome Sequencing

Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene

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