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Objective:To summarize the clinical phenotype and genotype features of 2 children with adenosine deaminase 2 (ADA2) deficiency, and to review the related literature so as to enhance the understanding of this disease.Methods:The phenotype and genotype of 2 cases with ADA2 deficiency who visited the Affiliated Hospital of Qingdao University from March to December 2019 were analyzed.Literature was searched from foreign and domestic databases and studied to summarize clinical and gene mutation characteristics of children with ADA2 deficiency.Results:(1) ADA2 gene mutation was found in both children.One case was characterized by recurrent fever, livedo reticularis, polyarteritis nodosa and immunodeficiency.The mutation site c. 571delC(p.Q191Sfs*5)of the ADA2 gene detected in this case was a homozygous mutation, which was a new mutation point and not reported in China or abroad previously.The other case was characterized by recurrent fever, panniculitis, vasculitis with legs, and immunodeficiency.The mutation site c. 1358A>G(p.Y453C)was a homozygous mutation that was not reported in China previously.(2)There were 171 cases of children diagnosed with ADA2 deficiency in foreign countries, but only 5 cases (3 previously reported cases and 2 cases in this study) were detected in China.The main clinical phenotypes were recurrent fever(5/5 cases), livedo reticularis(4/5 cases), panniculitis(1/5 cases), cutaneous gangrene(1/5 cases), growth retardation(1/5 cases), cerebral infarction(3/5 cases), humoral immunodeficiency(4/5 cases), blood system involvement(3/5 cases), and myalgia(2/5 cases), elevated inflammatory markers(C-reactive protein, erythrocyte sedimentation rate)(5/5 cases). Conclusions:Children with ADA2 deficiency have various clinical phenotypes, and a good understanding of phenotypes can improve the level of clinical diagnosis and treatment.The mutation point of c. 571delC is a novel ADA2 gene mutation type, which further enriches the ADA2 gene spectrum.
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Objective The 3243A ＞ G mutation in mitochondrial DNA is a common cause of the classical mitochondrial diseases characterized by neuro-muscular disorders.This study reports a rare case with the main manifestations of mitochondrial disease in children of mitochondrial cardiomyopathy and respiratory muscle damage.Methods The clinical characteristics,diagnosis and treatment,biochemical,pathological and genetic features of a 10-year-old girl were studied.Results The girl was admitted because of heart failure and respiratory failure at the age of 10.Ragged red fibers in skeletal muscles had been noticed.On her mitochondrial gene,3243A ＞ G mutation,Leu tRNA (UUR),was detected.The mutation rate in the peripheral blood cells was 94％.After the treatment with a high dose of creatine phosphate sodium,coenzyme Q10 and L-carnitine with assisted ventilation,the patient improved rapidly.The child was followed up for 2 years without recurrence.Meanwhile the growth,development and daily life were normal.Conclusions Cardiac and respiratory muscle impairments that appeared at the same time as the first manifestations of the children's mitochondrial disease is not common,and it is rare to have cardiomyopathy based mitochondrial gene 3243A ＞ G mutation is seldom seen clinically.Skeletal muscle biopsy and genetic test is the key for accurate diagnosis.Improving mitochondrial metabolism and assisted ventilation appear to be helpful treatments.
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Objective To compare the effect of routine ketogenic diet and every other day ketogenic diet on neurobehavioral damage induced by recurrent seizures in neonatal rats.Methods 48 postnatal day 8 (P8) SD rats were randomly divided into four groups with 12 in each group:the control group (CONT),the recurrent seizure group(RS+ND),recurrent seizure + routine ketogenic diet group(RS+KD) and recurrent seizure+ every other day ketogenic diet group(RS+KOD).The recurrent seizures model was induced by flurothyl at p9 and last for 8 days.After a day of fasting the postnatal 28 day rats were placed on either ordinary or ketogenic diet according to packet design.Plane righting experiment,cliff avoidance test and negative geotaxis test were used to assess the neurobehavioral performance at p35.Results (1) Plane righting experiment:the plane fighting time of RS+ ND group ((0.17±0.39) s) was significantly shorter than that of NS+ND group ((0.67 ±0.49) s) (P＜0.05) ; and the plane righting time of RS+KD group((0.58±0.52) s) was significantly longer than that of RS+ND group ((0.17±0.39) s) (P＜0.05).There was no statistical significance between RS+KOD group((0.17±0.39) s) and RS+ND group ((0.17±0.39) s) (P＞0.05).(2) Cliff avoidance test:the cliff avoidance time of RS+ND group ((12.58±4.83) s)was significantly longer than that of NS+ND group ((1.92±0.90) s),RS+KD group((3.33± 1.50)s) and RS+ KOD group (P＜0.05) ;and the cliff avoidance time of RS+KOD group((5.58± 1.93)s) was significant longer than that of RS+KD group ((3.33± 1.50) s) (P＜0.05).(3) Negative geotaxis test:the negative geotaxis time of RS+NDgroup((3.17±1.70)s) was significantly longer than that of NS+ND group((1.42±0.67) s) and RS+KD group ((1.42±0.52)s) (P＜0.05).There was no statistical significance between RS+KOD group and RS+ND group(P＞0.05).Conclusion The ketogenic diet can improve neurobehavioral damage caused by flurothyl-induced recurrent seizures in neonatal rats.The every other day KD group shows a weak intervention effect comparing with the routine KD group.
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Objective To investigate the intervention effect of ketogenic diet (KD) on neurobehavioral demages after flurothyl-induced recurrent neonatal seizures in rats and on the expression of ApoE.Methods Postnatal day 8 (P8) SD rats (quantity:48) were randomly divided into two groups:the non-seizure group (NS group,n =24) and the recurrent-seizure group (RS group,n =24).From P9,rats in RS group were subjected to recurrent seizures induced by volatile flurothyl 30 min each day for consecutive 8 days.While rats in NS group were placed into the container for an equal amount of time to their counterpart without exposuring to flurothyl.At P28,each group was divided into two groups again:non-seizure and normal diet group(NS + ND group,n =12),non-seizure and ketogenic diet group(NS + KD group,n =12),recurrent-seizure and normal diet group (RS + ND group,n =12),recurrent-seizure and ketogenic diet group(RS + KD group,n =12).At P42,neurodevelopmental indicators were monitored.ApoE protein levels in cerebral cortex were determined by western blot at P58.Results Neurodevelopmental indicators were analyzed at P42:in the plane righting experiment,the rats of group NS + ND (1.0 ±0.14) about the time of plane righting was significant different comparing with group RS + ND ((0.75 ±0.32) s) (P ＜ 0.05).There was no significant difference between group RS + KD and group RS + ND about the time of plane righting(P＞ 0.05).In the negative geotaxis reaction experiment,the rats of groups NS + KD and RS + ND((3.17 ± 0.58)s,(6.75 ± 0.75)s) about the time of negative geotaxis reaction were significant different comparing with group NS + ND ((1.58 ±0.52)s) (P＜0.05).Compared with group RS + ND,the group RS + KD in the time of negative geotaxis reaction was obviously shortened (P ＜ 0.05).In the cliff avoidance test,there were significant differences between group NS + ND、RS + KD ((5.75 ± 2.90) s,(9.50 ± 4.36) s) and group RS + ND ((14.00 ± 4.79) s) about the time of cliff avoidance (P ＜ 0.05).In western blot,the expression of ApoE in cerebral cortex in the RS + ND group (1.26 ± 0.30) was obviously increased compared with group NS + ND (0.78 ±0.12) (P＜0.05),and there had also significant difference between group RS + KD (0.89 ±0.10) and group RS + ND (P ＜ 0.05).Conclusion The neuroprotective effects of ketogenic diet on recurrent neonatal seizure-induced neurobehavioral demages may be associated with the reduction of ApoE in cerebral cortex.