PURPOSE: This study was performed to analyse urine gamma-hydroxybutyric acid(GHB) in children with seizures, and to investigate the pattern of seizures and neurologic abnormalities in children related with gamma-hydroxybutyric aciduria. METHODS: We reviewed retrospectively medical records of children who admitted to our hospital with seizures between August 1. 2001 and February 28. 2003. We compared urine GHB levels with controls, and also analyzed the clinical features of patients who showed increased urine GHB. RESULTS: The mean urine GHB was 1.7+/-1.6 mmol/mol cr in febrile seizures, 1.8+/-2.5 mmol/mol cr in non-febrile seizures, and 1.8+/-2.0 mmol/mol cr in controls. Compared with control group, there was no significant difference in urine GHB levels(P>0.05). In 8 of 64 children with seizures, GHB levels increased above 2 standard deviation of normal controls. The types of seizure in children who showed increased urine GHB were generalized tonic clonic seizure in 3 patients, complex partial seizure in 2 patients, febrile seizure in 2 patients, and benign Rolandic epilepsy in 1 patient. 3 patients showed neurologic abnormalities, 4 patients showed electroencephalographic abnormalities, and 2 patients of 6 patients who performed brain imaging study showed brain imaging abnormalities. CONCLUSION: Children with gamma-hydroxybutyric aciduria should be suspected succinic semialdehyde dehydrogenase deficiency as a cause of underlying disease.
Child* ; Epilepsy* ; Epilepsy, Rolandic ; Humans ; Medical Records ; Neuroimaging ; Retrospective Studies ; Seizures* ; Seizures, Febrile ; Succinate-Semialdehyde Dehydrogenase

OBJECTIVE: To explore the genetic basis for a child with succinate semialdehyde dehydrogenase deficiency. METHODS: Peripheral blood samples of the proband and his parents were collected and subjected to Sanger sequencing. High-throughput sequencing was used to verify the gene variants. Bioinformatic software was used to analyze the pathogenicity of the variant sites. RESULTS: Sanger sequencing showed that the proband carried a homozygous c.1529C>T (p.S510F) variant of the ALDH5A1 gene, for which his mother was a carrier. The same variant was not detected in his father. However, high-throughput sequencing revealed that the child and his father both had a deletion of ALDH5A1 gene fragment (chr6: 24 403 265-24 566 986). CONCLUSION The c.1529C>T variant of the ALDH5A1 gene and deletion of ALDH5A1 gene fragment probably underlay the disease in the child. High-throughput sequencing can detect site variation as well as deletion of gene fragment, which has enabled genetic diagnosis and counseling for the family.
Amino Acid Metabolism, Inborn Errors/genetics* ; Child ; Developmental Disabilities ; Humans ; Infant ; Mutation ; Succinate-Semialdehyde Dehydrogenase/genetics*

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder. This paper reports three cases of SSADH deficiency in infants. The infants developed the symptoms including developmental delay, intellectual disability, hypotonia, hyporeflexia and seizures. The electroencephalogram (EEG) showed background slowing and focal spike discharges in all of 3 patients. Head magnetic resonance imaging (MRI) demonstrated abnormalities in 2 patients, including basal ganglia damage and increased T2-weighted signal in bilateral cerebral peduncles. Urinary organic acid analysis with gas chromatography-mass spectrometry (GC-MS) revealed increased levels of 4-hydroxybutyrate (GHB) in 3 patients. SSADH deficiency was definitely diagnosed based on the clinical manifestations and the results of urinary organic acid analysis in the 3 children. It was concluded that early urine organic acid analysis is essential for children presenting with mental retardation, neuropsychiatric disturbance or epilepsy of unknown etiology.
Amino Acid Metabolism, Inborn Errors ; diagnosis ; therapy ; Developmental Disabilities ; Diagnosis, Differential ; Female ; Humans ; Infant ; Succinate-Semialdehyde Dehydrogenase ; deficiency

Aldehyde Oxidoreductases ; deficiency ; Child, Preschool ; Female ; Humans ; Metabolism, Inborn Errors ; diagnosis ; enzymology ; metabolism ; Succinate-Semialdehyde Dehydrogenase ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo detect potential mutation in ALDH5A1 gene for a family affected with succinic semialdehyde dehydrogenase deficiency diagnosed by clinical inspection and urine screening.

METHODSPolymerase chain reaction and direct DNA sequencing were carried out for the affected child and her parents. Suspected ALDH5A1 gene mutations were verified in 100 healthy controls to exclude polymorphisms.

RESULTSThe child was found to have carried 2 heterozygous missense mutations in the coding region of ALDH5A1 gene, namely c.527G>A and c.691G>A, for which her mother and father were respectively heterozygotes. The same mutations were not detected in 100 healthy controls. The child was also found to have carried two previously described polymorphisms including a heterozygous c.545C>T(derived from her father) and a homozygous c.538C>T(derived from her mother).

CONCLUSIONMissense mutations of c.527G>A and c.691G>A in the ALDH5A1 gene are responsible for the pathogenesis of the disease in this family.

Adult ; Amino Acid Metabolism, Inborn Errors ; enzymology ; ethnology ; genetics ; Amino Acid Sequence ; Animals ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Child, Preschool ; China ; ethnology ; Developmental Disabilities ; Female ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Polymorphism, Genetic ; Succinate-Semialdehyde Dehydrogenase ; deficiency ; genetics

OBJECTIVETo detect potential mutation in a Chinese family affected with succinic semialdehyde dehydrogenase deficiency.

METHODSGenomic 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.

RESULTSThe 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.

CONCLUSIONThe 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.

Amino Acid Metabolism, Inborn Errors ; ethnology ; genetics ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; methods ; Developmental Disabilities ; ethnology ; genetics ; Exons ; genetics ; Family Health ; Female ; Heterozygote ; Humans ; Infant ; Introns ; genetics ; Male ; Mutation ; Sequence Homology, Amino Acid ; Succinate-Semialdehyde Dehydrogenase ; deficiency ; genetics