Screening of inherited metabolic abnormalities in 56 children with intractable epilepsy

Abstract

Epilepsy is a common children's neural disease that is largely controlled by anti-epileptic drugs. Nevertheless, children experience repeated attacks that develop into intractable epilepsy (IE). The aim of the present study was to examine the inherited metabolic abnormalities in children with IE to provide early etiological and symptomatic treatment. Urine and blood samples of 56 children with IE served as the experimental group and 56 cases of children with IE, who were successfully treated served as the control group, and analyzed by gas chromatography-mass spectrometry and tandem mass spectrometry for the metabolic screening of amino, organic, and fatty acids. Urine routine, hepatic function, blood biochemistry, imageology of encephalon and brain stem-evoked potential (auditory and optical) were also examined. Of the 27 IE children confirmed as abnormal in urine and blood screening, there were 19 cases (70.3%) of hypoevolutism or retrogression of intelligence and motor function, 15 cases (55.5%) of brain stem-evoked potential and of encephalic computed tomography (CT) or magnetic resonance imaging (MRI) abnormality, 6 cases (22.2%) of abnormal family history and of abnormal blood biochemistry and blood gas analysis, and 5 cases (18.5%) with skin change and of abnormal hepatic function. Of the 27 cases, 11 cases (19.6%) were diagnosed with inherited metabolic diseases. Among the children in the control group, 3 cases showed abnormal urine test results, one of which had family history, one had hypoevolutism or retrogression of intelligence and motor function, one had brain stem-evoked potential and encephalic CT or MRI abnormality, while two of the 3 cases had inherited metabolic abnormalities. The correlation analysis revealed that abnormal urine test was significantly correlated with inherited metabolic abnormalities (P<0.05). Of the 56 IE patients, 25 cases (44.6%) were identified as abnormal under urine screening, and of the 25 cases, 6 cases had simple generalized seizure (24.0%), 5 cases had simple partial seizure (20.0%), 2 cases had multiple types of seizure (8.0%), and 12 cases had infantile spasms (48.0%). Six cases in the control group showed an abnormal urine test, with 3 cases of simple generalized seizure, 2 cases of simple partial seizure and 1 case of multiple types of seizure. The abnormal urine in infantile spasms was often the risk factor of IE. A total of 46 IE children underwent blood screening and 13 cases were diagnosed as abnormal. In conclusion, inherited metabolic abnormality was a common influential factor in the pathogenesis of IE, especially in infantile spasms. Screening of inborn metabolic abnormality in children with IE should be conducted as early as possible, to achieve early treatment and improve their prognosis.

Tandem Mass Spectrometry in Patients with Drug Resistant Epilepsy

“…In current study, four patients had abnormal elevated amino acids with age 1 to 5 years(67% of positive case), this is in contrast with the study by Liu et al 7 where 8% of his cases, respectively, had possible mitochondrial dysfunction.…”

“…These symptoms caused mostly by defective enzymes or transporters in metabolic pathways. Such defects lead to malfunctioning metabolism and accumulation of toxic intermediate metabolites 6. This agrees with Liu et al 7 study who applied metabolic screening to detect the blood and urinary metabolic components of 56 IE children, and 25 cases were confirmed with 12 types of abnormalities, (76%) confirmed with backward or regressive intelligent movement; cases (55.5%) with skull imaging abnormalities, (24.2%) with blood biochemistry and blood gas analysis abnormalities, including the increase of blood ammonia, and blood lactic acid and (18.5%) with skin change.…”

Epilepsy in selected neurometabolic diseases

“…Morfologia napadów padaczkowych jest różnorodna, najczęściej występują napady miokloniczne, ogniskowe z wtórnym uogólnieniem, uogólnione toniczno-kloniczne, kloniczne, toniczne, napady zgięciowe [11][12]. W badaniach laboratoryjnych stwierdza się [9][10][11][12][13]…”

“…[29,30]. W deficycie kofaktora molibdenowego w badaniach laboratoryjnych występuje obniżony poziom kwasu moczowego we krwi i w moczu, dodatni wynik badania sulfitestu (na obecność siarczynów w moczu), hipoksantyna w moczu, podwyższony poziom ksantyny, hipoksantyny, tauryny i S-sulfocysteiny [1][2][3]13]. W deficycie kofaktora molibdenowego typu1 (mutacja w genie MOCS1) istnienie możliwość leczenia cyklicznym monofosforanempiranopteryny (80-160 μg/kg/d) [29][30].…”

“…Do chwili obecnej opisano ponad 200 pacjentów z rozpoznaniem MTHFR [35][36]. Choroba prowadzi do podwyższonego stężenia homocysteiny, homocystynurii, obniżonego metioniny w osoczu [13]. Niski poziom metioniny powoduje niedobór S-adenozylometioniny [35][36].…”