ABSTRACT
Objective@#To study the clinical and laboratory diagnosis and follow-up of 4-hydroxy butyrate aciduria in children.@*Methods@#From June 2012 to July 2017, 9 cases in Tianjin Children′s Hospital were analyzed.According to their clinical features, multidimensional analysis was performed by using head magnetic resonance imaging (MRI), urine gas chromatography-mass spectrometry (GC/MS) semi-quantitative testing and gene mutation analysis of ALDH5A1.@*Results@#The onset age of the 9 cases was less than 1 year old, and all had psychomotor retardation, in which 4 cases with epileptic seizures, 1 case with consciousness disturbance and 1 case with involuntary movement.All the cases underwent head MRI and 4 cases showed bilateral symmetry pallidal lesions, including 1 case with symmetry abnormality of the midbrain cerebral peduncle, 1 case with encephalomalacia in left temporal cortex and 4 cases with widening of the ventricle and extracerebral space.By the urine GC/MS semi-quantitative testing, all 9 the cases showed increasing 4-hydroxy butyric acid and by the ALDH5A1 gene mutation analysis, all 9 the cases were detected with gene mutation (3 cases belonging to c. 1568C>T homozygous mutation, 1 case belonging to c. 839T>G homozygous mutation and the other 5 cases belonging to compound heterozygous mutation, which included c. 691G>A, c.1568C>T; c.1383_2delA, c.1568C>T; c.527G>A, c.691G>A; c.904G>A, c.1022C>A; c.398_399delA, c.638G>T). Nine cases were given symptomatic treatment, and 4 cases with epileptic seizures were given antiepileptic drugs.During the follow-up of the above 9 cases, 1 case died of status epilepticus, 1 case had been under control for 5 years, and 2 cases were effectively treated.Psychomotor retardation was improved in varying degrees in 8 cases.Involuntary movement disappeared in 1 case while 2 cases still showed increasing 4-hydroxy butyric acid by means of urine GC/MS semi-quantitative testing.@*Conclusions@#Most of 4-hydroxy butyrate aciduria occurs within 1 year old, with psychomotor development as the first manifestation, which can be associated with epilepsy.The head MRI is characte-rized by a symmetrical Globus pallid abnormal signal.Urine GC/MS shows an increase in 4-hydroxy butyrate, which is the basis for biochemical diagnosis of the disease.Its accumulation in the body mainly damages the central nervous system.ALDH5A1 is a disease-causing gene, in which c. 1568C>T site has a high mutation frequency, and it is speculated that this site may be a hot spot mutation in Chinese children.Patients with epilepsy may die from status epilepticus and may be used as a clinical indicator to judge the severity of the disease.There is no specific treatment, and the patients combined with epilepsy can be treated with anti-epileptic drugs.Valproic acid should be avoided as it can aggravate the condition.
ABSTRACT
Objective To study the clinical and laboratory diagnosis and follow-up of 4-hydroxy butyrate aciduria in children.Methods From June 2012 to July 2017,9 cases in Tianjin Children's Hospital were analyzed.According to their clinical features,multidimensional analysis was pedormed by using head magnetic resonance imaging (MRI),urine gas chromatography-mass spectrometry (GC/MS) semi-quantitative testing and gene mutation analysis of ALDH5A1.Results The onset age of the 9 cases was less than 1 year old,and all had psychomotor retardation,in which 4 cases with epileptic seizures,1 case with consciousness disturbance and 1 case with involuntary movement.All the cases underwent head MRI and 4 cases showed bilateral symmetry pallidal lesions,including 1 case with symmetry abnormality of the midbrain cerebral peduncle,1 case with encephalomalacia in left temporal cortex and 4 cases with widening of the ventricle and extracerebral space.By the urine GC/MS semi-quantitative testing,all 9 the cases showed increasing 4-hydroxy butyric acid and by the ALDH5A1 gene mutation analysis,all 9 the cases were detected with gene mutation (3 cases belonging to c.1568C ＞ T homozygous mutation,1 case belonging to c.839T ＞ G homozygous mutation and the other 5 cases belonging to compound heterozygous mutation,which included c.691G ＞ A,c.1568C ＞T;c.1383_2delA,c.1568C ＞ T;c.527G ＞ A,c.691G ＞ A;c.904G ＞ A,c.1022C ＞ A;c.398_399delA,c.638G ＞ T).Nine cases were given symptomatic treatment,and 4 cases with epileptic seizures were given antiepileptic drugs.During the follow-up of the above 9 cases,1 case died of status epilepticus,1 case had been under control for 5 years,and 2 cases were effectively treated.Psychomotor retardation was improved in varying degrees in 8 cases.Involuntarymovement disappeared in 1 case while 2 cases still showed increasing 4-hydroxy butyric acid by means of urine GC/MS semi-quantitative testing.Conclusions Most of 4-hydroxy butyrate aciduria occurs within 1 year old,with psychomotor development as the first manifestation,which can be associated with epilepsy.The head MRI is characterized by a symmetrical Globus pallid abnormal signal.Urine GC/MS shows an increase in 4-hydroxy butyrate,which is the basis for biochemical diagnosis of the disease.Its accumulation in the body mainly damages the central nervous system.ALDH5A1 is a disease-causing gene,in which c.1568C ＞ T site has a high mutation frequency,and it is speculated that this site may be a hot spot mutation in Chinese children.Patients with epilepsy may die from status epilepticus and may be used as a clinical indicator to judge the severity of the disease.There is no specific treatment,and the patients combined with epilepsy can be treated with anti-epileptic drugs.Valproic acid should be avoided as it can aggravate the condition.
ABSTRACT
<p><b>OBJECTIVE</b>To detect potential mutation in a Chinese family affected with succinic semialdehyde dehydrogenase deficiency.</p><p><b>METHODS</b>Genomic DNA was extracted from the peripheral blood samples of the proband, her family members and 100 healthy controls. All exons and flanking intronic regions of the ALDH5A1 gene were amplified by PCR and subjected to direct sequencing.</p><p><b>RESULTS</b>The proband was found to have compound heterozygous mutations of the ALDH5A1 gene, namely c.398_399delAA (p.N134X) and c.638G>T (p.R213L), for which her parents were both heterozygous carriers. The same mutations were not found among the 100 healthy controls.</p><p><b>CONCLUSION</b>The novel mutations of the ALDH5A1 gene probably underlie the pathogenesis of the disease in the infant, which also enriched the mutation spectrum of the ALDH5A1 gene.</p>