ABSTRACT
Objective@#To delineate the clinical and genetic features of two pedigrees affected with aromatic L-amino acid decarboxylase (AADC) deficiency.@*Methods@#The clinical features, family history and results of genetic testing of 2 patients with AADC deficiency were retrospectively analyzed.@*Results@#Both patients featured hypotension, developmental delay and oculogyric crisis during infancy.Genetic testing confirmed that they have respectively carried c. 714+ 4 (IVS6) A>T/c.175(exon2)G>A compound heterozygous variants and c. 714+ 4(IVS6)A>T homozygous variant.@*Conclusion@#The clinical manifestation of children with AADC deficiency may include hypotonia, developmental delay and paroxysmal oculogyric crisis. The combination of 3-O-methyldopa testing and variant analysis is not only very useful for early diagnosis, but also important for the evaluation of treatment effect and prognosis of the disease. Discovery of the novel variants has enriched the variant spectrum of AADC deficiency.
ABSTRACT
OBJECTIVE@#To delineate the clinical and genetic features of two pedigrees affected with aromatic L-amino acid decarboxylase (AADC) deficiency.@*METHODS@#The clinical features, family history and results of genetic testing of 2 patients with AADC deficiency were retrospectively analyzed.@*RESULTS@#Both patients featured hypotension, developmental delay and oculogyric crisis during infancy. Genetic testing confirmed that they have respectively carried c.714+ 4 (IVS6) A to T/c.175(exon2)G TO A compound heterozygous variants and c.714+ 4(IVS6)A to T homozygous variant.@*CONCLUSION@#The clinical manifestation of children with AADC deficiency may include hypotonia, developmental delay and paroxysmal oculogyric crisis. The combination of 3-O-methyldopa testing and variant analysis is not only very useful for early diagnosis, but also important for the evaluation of treatment effect and prognosis of the disease. Discovery of the novel variants has enriched the variant spectrum of AADC deficiency.
Subject(s)
Humans , Infant , Amino Acid Metabolism, Inborn Errors , Genetics , Aromatic-L-Amino-Acid Decarboxylases , Genetics , DNA Mutational Analysis , Genetic Testing , Pedigree , Retrospective StudiesABSTRACT
Objective To explore the change of endogenous glucocorticoids (GC) secretion after intracranial hemorrhage (ICH) of neonatal rats and the impact of Dexamethasone (DEX).Methods Ten-day-old Sprague-Dawley rat pups of both sexes were randomized into 11 groups:normal control group(CON group),sham operated group (SHAM group),ICH group(each of which was further subgrouped into 12 h group,24 h group and 72 h group according to execution time after the modeled operation),glucocorticoids receptor (GR) agonist intervene group (DEX group) and GR antagonist intervene group(RU486 group).The intracranial autologous blood injection model of ICH was employed.Neurological functional deficits was measured by neurological deficit score (NDS),the levels of cerebral homogenate GC were tested by the emission immunology method,and the pathologic change and the expression of GR in hippocampus CA1 were examined by using Nissl staining and immunofluorescence separately.Results (1) Seventy-two-hour after the modeled operation,NDS of rats in the ICH group reached (7.48 ± 2.19) scores.After intervened by DEX,NDS of rats in DEX group decreased to (3.15 ± 1.93) scores,significantly lower than in ICH group,the difference was significant (P ＜ 0.05).The necrotic neurons were found around the hematoma of rats in ICH group,while in DEX group,less necrotic neurons were found.(2)In ICH group,the GC level in cerebral homogenate climbed up to a peak of (1.359 1 ±0.308 5) μg/L at 12 h,and slowly went down.By the end of 72 h,the GC level was (0.951 0 ±0.036 1) μg/L,which was higher than those of the CON group[(0.621 3 ±0.039 3) μg/L],the difference was significant (P ＜ 0.05),while in the DEX group,the level of GC in cerebral homogenate showed no difference with statistics from CON group.(3)The mean integrated optical density (IOD) of GR in hippocampal CA1 of rats in the ICH group (1.282 4 ± 0.035 6) were much more smaller than those in the CON group (1.012 5 ± 0.027 3,P ＜ 0.05),which meant the down-regulated expression of GR.(4) No difference was found in the NDS,pathological change,GC level and GR expression between RU486 group and ICH group.DEX didn't effect the expression of GR.Conclusions ICH in neonatal rat disturbs the modulation of hypothalamus-pituitary-adrenal axis,with an increase in the GC level and less GR expression.Early application of exogenous GC helps protect the neurons.
ABSTRACT
Objective To explore the change of endogenous glucocorticoids (GC) secretion after intracranial hemorrhage (ICH) of neonatal rats and the impact of Dexamethasone (DEX).Methods Ten-day-old Sprague-Dawley rat pups of both sexes were randomized into 11 groups:normal control group(CON group),sham operated group (SHAM group),ICH group(each of which was further subgrouped into 12 h group,24 h group and 72 h group according to execution time after the modeled operation),glucocorticoids receptor (GR) agonist intervene group (DEX group) and GR antagonist intervene group(RU486 group).The intracranial autologous blood injection model of ICH was employed.Neurological functional deficits was measured by neurological deficit score (NDS),the levels of cerebral homogenate GC were tested by the emission immunology method,and the pathologic change and the expression of GR in hippocampus CA1 were examined by using Nissl staining and immunofluorescence separately.Results (1) Seventy-two-hour after the modeled operation,NDS of rats in the ICH group reached (7.48 ± 2.19) scores.After intervened by DEX,NDS of rats in DEX group decreased to (3.15 ± 1.93) scores,significantly lower than in ICH group,the difference was significant (P ＜ 0.05).The necrotic neurons were found around the hematoma of rats in ICH group,while in DEX group,less necrotic neurons were found.(2)In ICH group,the GC level in cerebral homogenate climbed up to a peak of (1.359 1 ±0.308 5) μg/L at 12 h,and slowly went down.By the end of 72 h,the GC level was (0.951 0 ±0.036 1) μg/L,which was higher than those of the CON group[(0.621 3 ±0.039 3) μg/L],the difference was significant (P ＜ 0.05),while in the DEX group,the level of GC in cerebral homogenate showed no difference with statistics from CON group.(3)The mean integrated optical density (IOD) of GR in hippocampal CA1 of rats in the ICH group (1.282 4 ± 0.035 6) were much more smaller than those in the CON group (1.012 5 ± 0.027 3,P ＜ 0.05),which meant the down-regulated expression of GR.(4) No difference was found in the NDS,pathological change,GC level and GR expression between RU486 group and ICH group.DEX didn't effect the expression of GR.Conclusions ICH in neonatal rat disturbs the modulation of hypothalamus-pituitary-adrenal axis,with an increase in the GC level and less GR expression.Early application of exogenous GC helps protect the neurons.