Screening of Inherited Metabolic Disorders in Infants with Infantile Spasms

Liu, Xiaoming; Li, Rui; Chen, Shengzhi; Sang, Yan; Chen, Jiao

doi:10.1007/s12013-014-0404-8

Cited by 14 publications

(13 citation statements)

References 12 publications

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“…All four children with findings suggestive of neurometabolic disorders on initial MRI, but who had not been previously diagnosed with a metabolic condition, were found to have metabolic diagnoses on further testing, underscoring the importance of targeted evaluation in this subgroup. Although a recent study from China reported a higher rate (22%) of inborn errors of metabolism in infants with newly diagnosed spasms, neuroimaging was abnormal in 62% of reported cases, and their cohort included disorders which are diagnosed by routine newborn screening in the United States, such as phenylketonuria and biotin deficiency.…”

Section: Discussionmentioning

confidence: 99%

How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium

et al. 2015

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SUMMARYObjective: To prospectively evaluate the etiology of new-onset infantile spasms and evaluate the yield of genetic and metabolic investigations in those without obvious cause after initial clinical evaluation and magnetic resonance imaging (MRI). Methods: Twenty-one U.S. pediatric epilepsy centers prospectively enrolled infants with newly diagnosed West syndrome in a central database. Etiology and investigations performed within 3 months of diagnosis were documented. Results: From June 2012 to June 2014, a total of 251 infants were enrolled (53% male). A cause was identified in 161 (64.4%) of 250 cases (genetic,14.4%; genetic-structural, 10.0%; structural-congenital, 10.8%; structural-acquired, 22.4%; metabolic, 4.8%; and infectious, 2.0%). An obvious cause was found after initial clinical assessment (history and physical examination) and/or MRI in 138 of 161, whereas further genetic and metabolic studies were revealing in another 23 cases. Of 112 subjects without an obvious cause after initial evaluation and MRI, 81 (72.3%) had undergone genetic testing, which showed a causal abnormality in 23.5% and a variant of unknown significance in 14.8%. Although metabolic studies were done in the majority (serum, 79.5%; urine, 69.6%; and cerebrospinal fluid [CSF], 38.4%), these revealed an etiology in only five cases (4.5%). No correlation was found between type of health insurance (public vs. private) and either genetic or metabolic testing. Significance: Clinical evaluation and MRI provide a specific diagnosis in 55% of children presenting with West syndrome. We propose that a cost-effective workup for those without obvious cause after initial clinical evaluation and MRI includes an array comparative genomic hybridization (aCGH) followed by an epilepsy gene panel if the microarray is not definitive, serum lactate, serum amino acids, and urine organic acids.

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Section: Discussionmentioning

confidence: 99%

How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium

et al. 2015

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“…DiGeorge syndrome with chromosomal 22q21.2 deletion; methylmalonic acidaemia) a radial micro‐columnar pattern is seen in a generalized distribution throughout all lobes of the cortex in both hemispheres, rather than confined to a focal zone, interpreted as a generalized delay or arrest in cortical maturation . The incidence of epilepsy in early infancy in these generalized genetic and metabolic disorders is many times higher than age‐matched controls; seizure types vary from severe infantile epilepsies such as infantile spasms, to myoclonic epilepsy, to focal and generalized seizures .…”

Section: Focal Cortical Dysplasia Type Imentioning

confidence: 99%

Review: The international consensus classification of Focal Cortical Dysplasia – a critical update 2018

Najm

Sarnat

Blümcke

2018

Neuropathology Appl Neurobio

169

153

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The Diagnostic Methods commission of the International League against Epilepsy (ILAE) released a first international consensus classification of Focal Cortical Dysplasia (FCD) in 2011. Since that time, this FCD classification has been widely used in clinical diagnosis and research (more than 740 papers cited in Pubmed between 1/1/2012 and 7/1/2017). Herein, we review the new data that will inform and revise the FCD classification. Many recent papers described moleculargenetic characteristics in FCD type II including multiple mutations in the mTOR pathway. In addition, the electro-clinico-imaging phenotype and surgical outcomes of FCD type II (in particular type IIb) were further defined and validated. These results pave the way for the design of an integrated clinico-pathological and genetic classification system, as recently recommended by the WHO for the classification of malignant brain tumours.On the other hand, little new information was acquired on FCD types I and III. Focal cortical dysplasia type I subtypes are still lacking a comprehensive description of clinical phenotypes, reproducible imaging characteristics, and specific molecular/genetic biomarkers. Associated FCD III subtypes also became rare in published literature. Despite temporal lobe epilepsy being the most common focal epilepsy in adults, we have not identified neurophysiological, imaging, histopathological and/or genetic biomarkers to reliably classify FCD III with or without hippocampal sclerosis. In respect of pathogenesis, FCD adjacent to a non-developmental, postnatally acquired lesion is difficult to explain and perhaps does not exist. This update may help foster shared efforts towards a better understanding of FCD, potential future updates of classification and novel targeted treatments.

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“…Approximately 90% of patients develop GA-I in early childhood, and the remaining 10% of patients show mild symptoms or no symptoms (3). In recent years, GA-I in the Chinese population has gained increasing interest (4–7). However, a large number of children do not receive a timely diagnosis and proper treatment clinically.…”

Section: Introductionmentioning

confidence: 99%

Clinical and laboratory analysis of late-onset glutaric aciduria type I (GA-I) in Uighur: A report of two cases

Zhang

Luo

2016

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate the clinical, biochemical and genetic mutation characteristics of two cases of late-onset glutaric aciduria type I (GA-I) in Uighur. The clinical data and glutaryl-CoA dehydrogenase (GCDH) genetic test results of two cases of late-onset GA-I in Uighur were collected and analyzed, and reviewed with relevant literature. One patient with late-onset GA-I primarily exhibited clinical intermittent headache, while the other patient was asymptomatic. The urinary organic acid analysis detected a large number of glutaric acid and 3-hydroxy glutaric acid, 3-hydroxy-propionic acid. One patient exhibited white matter degeneration in cranial magnetic resonance imaging (MRI) and the other patient showed no abnormality. The two patients both exhibited c. 1204C >T, p.R402W, heterozygous mutation, and c. 532G >A, p.G178R, heterozygous mutation. Besides central nervous system infectious diseases, patients with clinical headache, cranial MRI-suggested bilateral temporal lobe arachnoid cyst and abnormal signals in the basal ganglia should be highly suspected as late-onset GA-I. Early diagnosis and correct treatment are key to improve its prognosis.

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Screening of Inherited Metabolic Disorders in Infants with Infantile Spasms

Cited by 14 publications

References 12 publications

How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium

How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium

Review: The international consensus classification of Focal Cortical Dysplasia – a critical update 2018

Clinical and laboratory analysis of late-onset glutaric aciduria type I (GA-I) in Uighur: A report of two cases

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