MRI and MRS in HMG-CoA lyase deficiency

Yalçınkaya, Cengiz; Di̇nçer, Alp; Gündüz, Erem; Fıçıcıoğlu, Can; Koçer, Naci; Aydın, Ahmet

doi:10.1016/s0887-8994(99)00013-2

Cited by 48 publications

(18 citation statements)

References 8 publications

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“…With increasing age, white matter changes (which most probably correspond to dys-and subsequent demyelination) become obvious. In some phenotypes the white matter lesions are dominantly periventricular or subcortical; in others lesions they may be found in both periventricular and subcortical, or in exclusively subcortical locations [33,34].…”

Section: -Hydroxy-3-methylglutaryl (Hmg)-coenzyme a Lyase Deficiencymentioning

confidence: 99%

Diffusion-weighted MR imaging in leukodystrophies

Patay

2005

Eur Radiol

105

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Leukodystrophies are genetically determined metabolic diseases, in which the underlying biochemical abnormality interferes with the normal build-up and/or maintenance of myelin, which leads to hypo-(or arrested) myelination, or dysmyelination with resultant demyelination. Although conventional magnetic resonance imaging has significantly contributed to recent progress in the diagnostic work-up of these diseases, diffusion-weighted imaging has the potential to further improve our understanding of underlying pathological processes and their dynamics through the assessment of normal and abnormal diffusion properties of cerebral white matter. Evaluation of conventional diffusionweighted and ADC map images allows the detection of major diffusion abnormalities and the identification of various edema types, of which the socalled myelin edema is particularly relevant to leukodystrophies. Depending on the nature of histopathological changes, stage and progression gradient of diseases, various diffusionweighted imaging patterns may be seen in leukodystrophies. Absent or low-grade myelin edema is found in mucopolysaccharidoses, GM gangliosidoses, Zellweger disease, adrenomyeloneuropathy, L-2-hydroxyglutaric aciduria, non-ketotic hyperglycinemia, classical phenylketonuria, Van der Knaap disease and the vanishing white matter, medium grade myelin edema in metachromatic leukodystrophy, X-linked adrenoleukodystrophy and HMG coenzyme lyase deficiency and high grade edema in Krabbe disease, Canavan disease, hyperhomocystinemias, maple syrup urine disease and leukodystrophy with brainstem and spinal cord involvement and high lactate.

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Section: -Hydroxy-3-methylglutaryl (Hmg)-coenzyme a Lyase Deficiencymentioning

confidence: 99%

Diffusion-weighted MR imaging in leukodystrophies

Patay

2005

Eur Radiol

105

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“…We further investigated the mechanisms underlying the IF hypophosphorylation induced by HMG, the major accumulating compound in HMG lyase deficiency, using the striatum that is mainly compromised in patients affected by this disorder (Sweetman and Wlliams 2001;van der Knaap et al 1998;Yalçinkaya et al 1999;Yýlmaz et al 2006).…”

Section: Resultsmentioning

confidence: 99%

“…Lethargy, coma, convulsions, metabolic acidosis, and hypoketotic hypoglycemia, accompanied by vomiting and mild liver alterations are common findings during episodes of metabolic decompensation (Gibson et al 1988). Generalized cerebral edema, structural abnormalities in the white matter (hypomyelinization) of cerebral cortex, and mainly in the basal ganglia are commonly observed on MRI (Yalçinkaya et al 1999;Yýlmaz et al 2006;Zafeiriou et al 2007).…”

mentioning

confidence: 99%

NMDA Receptors and Oxidative Stress Induced by the Major Metabolites Accumulating in HMG Lyase Deficiency Mediate Hypophosphorylation of Cytoskeletal Proteins in Brain From Adolescent Rats: Potential Mechanisms Contributing to the Neuropathology of This Disease

et al. 2015

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Neurological symptoms and cerebral abnormalities are commonly observed in patients with 3-hydroxy-3-methylglutaryl-CoA lyase (HMG lyase) deficiency, which is biochemically characterized by predominant tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), 3-methylglutaric (MGA), and 3-methylglutaconic (MGT) acids. Since the pathogenesis of this disease is poorly known, the present study evaluated the effects of these compounds on the cytoskeleton phosphorylating system in rat brain. HMG, MGA, and MGT caused hypophosphorylation of glial fibrillary acidic protein (GFAP) and of the neurofilament subunits NFL, NFM, and NFH. HMG-induced hypophosphorylation was mediated by inhibiting the cAMP-dependent protein kinase (PKA) on Ser55 residue of NFL and c-Jun kinase (JNK) by acting on KSP repeats of NFM and NFH subunits. We also evidenced that the subunit NR2B of NMDA receptor and Ca(2+) was involved in HMG-elicited hypophosphorylation of cytoskeletal proteins. Furthermore, the antioxidants L-NAME and TROLOX fully prevented both the hypophosphorylation and the inhibition of PKA and JNK caused by HMG, suggesting that oxidative damage may underlie these effects. These findings indicate that the main metabolites accumulating in HMG lyase deficiency provoke hypophosphorylation of cytoskeleton neural proteins with the involvement of NMDA receptors, Ca(2+), and reactive species. It is presumed that these alterations may contribute to the neuropathology of this disease.

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“…MRS allows noninvasive monitoring of the response to therapy. Decreases of NAA and elevations of myoinositol and choline in 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency (a deficiency of leucine metabolism), when combined with routine MRI findings of multiple coalescent white matter lesions of the periventricular white matter and arcuate fibers, may be a signature fingerprint for diagnosis of this disorder [45]. 1 H MRS has been used to study patients with urea cycle disorders [34,35].…”

Section: Amino Acid Disordersmentioning

confidence: 99%

Imaging of neurogenetic and neurometabolic disorders of childhood

Gropman

2004

Curr Neurol Neurosci Rep

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Magnetic resonance imaging (MRI) has emerged as a powerful tool in the study of normal and abnormal brain structure, function, and biochemistry. In particular, functional MRI has come into its own as a tool to study normal and abnormal brain functions such as learning, memory, and motor learning, as well as delineation of neurogenetic cognitive phenotypes. White matter microstructure can be studied using diffusion tensor imaging, which may allow abnormal white matter to be visualized prior to abnormalities on anatomic MRI. Magnetic resonance spectroscopy, a noninvasive method to study brain biochemistry, may allow for the delineation of regional metabolic changes as a result of disease progression and/or therapeutic intervention. With MRI techniques, one can investigate the relationship between structure, function, genes, and behavior. This report discusses the research applications of MRI to the study of neurogenetic disorders of childhood.

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MRI and MRS in HMG-CoA lyase deficiency

Cited by 48 publications

References 8 publications

Diffusion-weighted MR imaging in leukodystrophies

Diffusion-weighted MR imaging in leukodystrophies

NMDA Receptors and Oxidative Stress Induced by the Major Metabolites Accumulating in HMG Lyase Deficiency Mediate Hypophosphorylation of Cytoskeletal Proteins in Brain From Adolescent Rats: Potential Mechanisms Contributing to the Neuropathology of This Disease

Imaging of neurogenetic and neurometabolic disorders of childhood

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