Diagnosis and long-term follow-up of 4-hydroxy butyrate aciduria in 9 cases
10.3760/cma.j.issn.2095-428X.2019.20.010
- VernacularTitle: 4羟基丁酸尿症9例诊断及长期随访
- Author:
Wenxuan FAN
1
;
Jianbo SHU
2
;
Hong WANG
1
;
Yuqin ZHANG
1
Author Information
1. Department of Neurology, Tianjin Children′s Hospital, Tianjin 300134, China
2. Tianjin Pediatric Research Institute, Tianjin Children′s Hospital, Tianjin 300134, China
- Publication Type:Journal Article
- Keywords:
4-hydroxy butyrate aciduria;
Clinical feature;
Head magnetic resonance imaging;
Urine gas chromatography-mass spectrometry semi-quantitative testing;
ALDH5A1 gene mutation;
Follow-up
- From:
Chinese Journal of Applied Clinical Pediatrics
2019;34(20):1560-1564
- CountryChina
- Language:Chinese
-
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.
