Glucide metabolism disorders (excluding glycogen myopathies)

Klepper, Joerg

doi:10.1016/b978-0-444-59565-2.00036-8

Cited by 4 publications

(5 citation statements)

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“…Although G1D is still considered to be a rare disorder, estimates suggest that it accounts for approximately 1% of idiopathic generalized epilepsies and approximately 10% of early-onset absence epilepsies . On the basis of these estimates and the fact that milder phenotypes that consist of less severe symptoms are often not subject to genotyping, G1D is believed to be more common than current prevalence rates would indicate . Cerebrospinal fluid glucose levels are not always determined and may even be normal, limiting their diagnostic reliability.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Cerebrospinal fluid glucose levels are not always determined and may even be normal, limiting their diagnostic reliability. Thus, G1D diagnosis is likely to be dominated by ascertainment biases that result from phenotypic identification.…”

mentioning

confidence: 99%

“…5 On the basis of these estimates and the fact that milder phenotypes that consist of less severe symptoms are often not subject to genotyping, G1D is believed to be more common than current prevalence rates would indicate. 6,7 Cerebrospinal fluid glucose levels are not always determined and may even be normal, limiting their diagnostic reliability. Thus, G1D diagnosis is likely to be dominated by ascertainment biases that result from phenotypic identification.…”

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confidence: 99%

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Clinical Aspects of Glucose Transporter Type 1 Deficiency

Hao

Kelly

et al. 2017

JAMA Neurol

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IMPORTANCE Case reports regularly document unique or unusual aspects of glucose transporter type 1 deficiency (G1D). In contrast, population studies from which to draw global inferences are lacking. Twenty-five years after the earliest case reports, this deficiency still particularly affects treatment and prognostic counseling.OBJECTIVE To examine the most common features of G1D. DESIGN, SETTING, AND PARTICIPANTSIn this study, data were collected electronically from 181 patients with G1D through a web-based, worldwide patient registry from December 1, 2013, through December 1, 2016. The study used several statistical methods tailored to address the age at onset of various forms of G1D, associated manifestations, natural history, treatment efficacy, and diagnostic procedures. These factors were correlated in a predictive mathematical model designed to guide prognosis on the basis of clinical features present at diagnosis. RESULTS A total of 181 patients with G1D were included in the study (92 [50.8%] male and 89 female [49.2%]; median age, 9 years; age range, 0-65 years). As previously known, a relatively large variety of common phenotypes are characteristic of the G1D syndrome, including movement disorders, absence epilepsy (typical and atypical), and myoclonic and generalized epilepsies. The 3 main novel results are (1) the feasibility of effective dietary therapies (such as the modified Atkins diet) other than the ketogenic diet, (2) the relatively frequent occurrence (one-fourth of cases) of white matter magnetic resonance imaging abnormalities, and (3) the favorable effect of early diagnosis and treatment regardless of treatment modality and mutation type. In fact, the most important factor that determines outcome is age at diagnosis, as reflected in a predictive mathematical model. CONCLUSIONS AND RELEVANCEThe results reveal several changing notions in the approach to G1D syndrome diagnosis and treatment, such as the perceived absolute requirement for a ketogenic diet, the assumed lack of structural brain defects, and the potential existence of genotype-phenotype correlations, all of which are contested by the registry data.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Clinical Aspects of Glucose Transporter Type 1 Deficiency

Hao

Kelly

et al. 2017

JAMA Neurol

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“…Global deletion of Pank1 in addition to Pank2 results in reduced brain CoA in pups and transient hind limb dragging prior to death at about two weeks of age [ 13 ]. Pank2 knockout mice on a pantothenate deficient diet [ 15 ] or a low carbohydrate/high fat diet [ 16 ] exhibited movement disorders; however, it is not known whether brain CoA was altered or whether diet-induced perturbations in whole-body glucose homeostasis contributed to the neuromuscular phenotype of the animals [ 17 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice

et al. 2015

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BackgroundPantothenate kinase-associated neurodegeneration, PKAN, is an inherited disorder characterized by progressive impairment in motor coordination and caused by mutations in PANK2, a human gene that encodes one of four pantothenate kinase (PanK) isoforms. PanK initiates the synthesis of coenzyme A (CoA), an essential cofactor that plays a key role in energy metabolism and lipid synthesis. Most of the mutations in PANK2 reduce or abolish the activity of the enzyme. This evidence has led to the hypothesis that lower CoA might be the underlying cause of the neurodegeneration in PKAN patients; however, no mouse model of the disease is currently available to investigate the connection between neuronal CoA levels and neurodegeneration. Indeed, genetic and/or dietary manipulations aimed at reducing whole-body CoA synthesis have not produced a desirable PKAN model, and this has greatly hindered the discovery of a treatment for the disease.Objective, Methods, Results and ConclusionsCellular CoA levels are tightly regulated by a balance between synthesis and degradation. CoA degradation is catalyzed by two peroxisomal nudix hydrolases, Nudt7 and Nudt19. In this study we sought to reduce neuronal CoA in mice through the alternative approach of increasing Nudt7-mediated CoA degradation. This was achieved by combining the use of an adeno-associated virus-based expression system with the synapsin (Syn) promoter. We show that mice with neuronal overexpression of a cytosolic version of Nudt7 (scAAV9-Syn-Nudt7cyt) exhibit a significant decrease in brain CoA levels in conjunction with a reduction in motor coordination. These results strongly support the existence of a link between CoA levels and neuronal function and show that scAAV9-Syn-Nudt7cyt mice can be used to model PKAN.

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“…In the expectant mother, glucose is found at levels 25-30% higher than in the fetus, and it is transported to the fetus by concentration gradients and simple diffusion and through the action of transporters. In the fetus, the predominant transporter is GLUT-1, which has a high affinity for glucose and facilitates its passage through tissues [28].…”

Section: Maternal Provision Of Glucose To the Fetusmentioning

confidence: 99%

Neonatal Hypoglycemia

Barbosa¹,

Júnior²,

Lima³

2018

Selected Topics in Neonatal Care

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Hypoglycemia is the most frequent metabolic abnormality in the newborn, but no consensus exists on what level of blood glucose is able to protect the brain and influence the child's neural development and which is the best course of management in cases labeled as hypoglycemia. Early diagnosis, urgent treatment, and prevention of future episodes of hypoglycemia are the cornerstones of management, now supported by recent advances in molecular genetics and in our understanding of the pathophysiology of neonatal hypoglycemia, particularly the pathogenesis of congenital hyperinsulinemic hypoglycemia.

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Glucide metabolism disorders (excluding glycogen myopathies)

Cited by 4 publications

References 32 publications

Clinical Aspects of Glucose Transporter Type 1 Deficiency

Clinical Aspects of Glucose Transporter Type 1 Deficiency

Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice

Neonatal Hypoglycemia

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