GM1 Gangliosidosis, Late Infantile Onset Dystonia, and T2 Hypointensity in the Globus Pallidus and Substantia Nigra

Vieira, José Pedro; Conceição, Carla; Scortenschi, Ecaterina

doi:10.1016/j.pediatrneurol.2013.02.003

Cited by 15 publications

(12 citation statements)

References 4 publications

(10 reference statements)

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“…CNS: Hypomyelination is the most common finding . Additionally, T1‐hyperintense and T2‐hypointese signals within the thalami and mild T2‐hyperintense signals in the caudate nucleus and putamen are consistently seen . In juvenile‐onset GM1 gangliosidosis, progressive cerebral atrophy with secondary ventriculomegaly has been reported.…”

Section: Glossarymentioning

confidence: 99%

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Wagner

Poretti

Benson

et al. 2016

Journal of Neuroimaging

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Genetic skeletal disorders (GSDs) are a heterogeneous group characterized by an intrinsic abnormality in growth and (re-)modeling of cartilage and bone. A large subgroup of GSDs has additional involvement of other structures/organs beside the skeleton, such as the central nervous system (CNS). CNS abnormalities have an important role in long-term prognosis of children with GSDs and should consequently not be missed. Sensitive and specific identification of CNS lesions while evaluating a child with a GSD requires a detailed knowledge of the possible associated CNS abnormalities. Here, we provide a pattern-recognition approach for neuroimaging findings in GSDs guided by the obvious skeletal manifestations of GSD. In particular, we summarize which CNS findings should be ruled out with each GSD. The diseases (n = 180) are classified based on the skeletal involvement (1. abnormal metaphysis or epiphysis, 2. abnormal size/number of bones, 3. abnormal shape of bones and joints, and 4. abnormal dynamic or structural changes). For each disease, skeletal involvement was defined in accordance with Online Mendelian Inheritance in Man. Morphological CNS involvement has been described based on extensive literature search. Selected examples will be shown based on prevalence of the diseases and significance of the CNS involvement. CNS involvement is common in GSDs. A wide spectrum of morphological abnormalities is associated with GSDs. Early diagnosis of CNS involvement is important in the management of children with GSDs. This pattern-recognition approach aims to assist and guide physicians in the diagnostic work-up of CNS involvement in children with GSDs and their management.

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Section: Glossarymentioning

confidence: 99%

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Wagner

Poretti

Benson

et al. 2016

Journal of Neuroimaging

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“…Repeat scans over the years showed susceptibility effects from progressive paramagnetic iron deposition. This has been uncommonly reported in the literature . Distribution of the deposition is typically in a “wish bone” pattern with the medial and lateral parts of globus pallidi forming the forked ends and the extension to the anterior SN and red nucleus forming the stem of the wish bone.…”

Section: Case Reportmentioning

confidence: 91%

“…). In GM1 gangliosidosis, this deposition is owing to iron overload resulting from a defect in intralysosomal recycling …”

Section: Case Reportmentioning

confidence: 99%

Chronic GM1 Gangliosidosis with Characteristic “Wish Bone Sign” on Brain MRI. Another Type of Neurodegeneration with Brain Iron Accumulation?

Hajirnis

Udwadia-Hegde

2015

Movement Disord Clin Pract

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This 27-year-old female presented with delay in motor milestones noted in infancy followed by slowly progressive motor disability starting at around 3 to 4 years of age and by speech difficulties appearing shortly thereafter.She was born at term from nonconsanguineous healthy parents. Family history was negative. She started to walk late, at 2 years of age, with an unsteady gait. She developed normal speech until around 3 years of age, when she could speak approximately three-to four-word sentences, after which she was noted to have started regressing in her motor followed by language milestones, which started with a stammer. She progressed over the next few years from being ataxic for a while followed by development of marked generalized dystonia, which has slowly progressed since then, along with significant oromotor dystonia. Speech impairment worsened to the point of unintelligibility in the subsequent years. Cognitively, she remained well with no evidence of deterioration. No seizures were ever noted. Furthermore, no visual impairment was observed. Her subsequent clinical course over the years is characterized by progressive spastic-dystonic tetraparesis with anarthria with marked oromotor dystonia.Findings on general physical examination when first observed by us at 18 years of age were normal with no obvious dysmorphic features. Neurological examination revealed extrapyramidal signs with severe generalized dystonia and rigidity. Speech was severely impaired because of oromandibular dystonia. The remainder of her other systemic examination was unremarkable with no evidence of organomegaly. Fundoscopy revealed no abnormality.Workup for her over several years included routine blood tests, alpha-fetoprotein, vitamin E, copper, and ceruloplasmin titers, which were negative. Metabolic workup, including blood and urine chromatography of amino acids and urinary organic acids, as well as peroxisomal function tests, were unremarkable. Neurophysiology included visual and brainstem auditory evoked potentials, electromyography, and nerve conduction velocities, which were all normal.MRI done at 3.5 years of age was reported to show patchy hyperintense lesions in the para ventricular deep white matter (WM) along the posterior part of bodies of the lateral ventricles and occipital horns on both sides on T2-weighted images. Repeat MRI brain at 13 and 25 years, apart from showing the previous WM changes, also showed bilateral hypointensities of the globus pallidus (GP) on T1-weighted images with corresponding low signal intensity on gradient-echo T2-weighted images, which was consistent with susceptibility effects from paramagnetic iron deposition. The susceptibility-weighted images (SWIs) done on the last scan revealed progression of the iron deposition involving the GP and spreading to the anterior SN. However, specific signal-intensity abnormalities, such as the "eye-of-the-tiger" sign, was not observed in any of the scans.In view of the above-described findings, DNA sequence analysis of the PANK2 gene was sent in suspic...

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“…The type is denoted as infantile (I), juvenile (J), or adult (A). Reference number (1) [Ong et al, 2012], (2) [Steenweg et al, 2010], (3) , (4) [Erol et al, 2006], (5) [van der Voorn et al, 2005], (6) [Di Rocco et al, 2005], (7) [Lin et al, 2000], (8) [Al-Essa et al, 1999], (9) [Shen et al, 1998], (10) [Chen et al, 1998], (11) [Kobayashi and Takashima, 1994], (12) [De Grandis et al, 2009], (13) [Vieira et al, 2013], (14) [ Roze et al, 2005], (15) [Campdelacreu et al, 2002], (16) [Tanaka et al, 1995], (17) , (18) [Nardocci et al, 1993], (19) [Inui et al, 1990].…”

Section: Materials and Methods Patient Recruitment And Descriptionmentioning

confidence: 99%

“…Only two publications describe imaging in three Type II GM1 gangliosidosis patients. Hypointensity of the globus pallidus, hyperintensity of the putamen, and iron deposition were noted in both reports [De Grandis et al, 2009;Vieira et al, 2013], while atrophy was noted in one [De Grandis et al, 2009]. A third article described MRI findings, however, the type of GM1 gangliosidosis was difficult to classify, based on the description given [Muthane et al, 2004].…”

mentioning

confidence: 97%

MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis

Regier

Kwon

Johnston

et al. 2015

American J of Med Genetics Pt A

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Background GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in GLB1, encoding β-galactosidase. The range of severity is from type I infantile disease, lethal in early childhood, to type III adult onset, resulting in gradually progressive neurological symptoms in adulthood. The intermediate group of patients has been recently classified as having type II late infantile subtype with onset of symptoms at one to three years of age or type II juvenile subtype with symptom onset at 2-10 years. To characterize disease severity and progression, six Late infantile and nine juvenile patients were evaluated using magnetic resonance imaging (MRI), and MR spectroscopy (MRS). Since difficulties with ambulation (gross motor function) and speech (expressive language) are often the first reported symptoms in type II GM1, patients were also scored in these domains. Deterioration of expressive language and ambulation was more rapid in the late infantile patients. Fourteen MRI scans in six Late infantile patients identified progressive atrophy in the cerebrum and cerebellum. Twenty-six MRI scans in nine juvenile patients revealed greater variability in extent and progression of atrophy. Quantitative MRS demonstrated a deficit of N-acetylaspartate in both the late infantile and juvenile patients with greater in the late infantile patients. This correlates with clinical measures of ambulation and expressive language. The two subtypes of type II GM1 gangliosidosis have different clinical trajectories. MRI scoring, quantitative MRS and brain volume correlate with clinical disease progression and may serve as important minimally-invasive outcome measures for clinical trials.

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GM1 Gangliosidosis, Late Infantile Onset Dystonia, and T2 Hypointensity in the Globus Pallidus and Substantia Nigra

Abstract: GM1 gangliosidosis is a rare disease due to mutations in the GLB1 gene and

Cited by 15 publications

References 4 publications

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Chronic GM1 Gangliosidosis with Characteristic “Wish Bone Sign” on Brain MRI. Another Type of Neurodegeneration with Brain Iron Accumulation?

MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis

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