Clinical And Genetic Characteristics Of Mitochondrial Disease Caused By Nuclear Gene Mutation In 2 Cases

Objective:To retrospectively analyze the clinical data,laboratory tests and gene mutation results of two children with mitochondrial disease caused by nuclear gene mutation,aiming to improve the understanding of this type of disease,to achieve early diagnosis and guide clinical treatment.Methods: Two children with mitochondrial disease caused by nuclear mutations in our hospital were selected as subjects.The clinical manifestations,physical examination,laboratory examination,neurological imaging findings and whole exome sequencing results were retrospectively analyzed.Results: Case 1 was a 3-month-old baby girl with onset of neonatal period.The main clinical manifestations were yellow skin staining,abnormal blood coagulation function and mental retardation.Physical examination revealed small size,small head deformity,nystagmus,yellow skin staining,enlarged liver,unable to follow light,chasing sound,less limb activity,low muscle tone.Liver function suggested that alanine aminotransferase,total bilirubin and direct bilirubin were elevated,alpha-fetoprotein was elevated;hematuria metabolism was negative;gene detection showed DGUOK gene compound heterozygous mutation in proband,respectively c.396G> A mutation(parental origin),c.173T>C mutation(marental origin),and the child died at home at 5months.Case 2 was a 1-year-old girl with asthma,fever with lethargy,and status epilepticus as the main clinical manifestations.Physical examination showed shallow coma,showing nasal fan,shortness of breath,cyanosis of the lips,enlarged liver,low muscle tone;blood gas analysis indicated severe metabolic acidosis,hyperlactosis;negative hematuria metabolism screening;cranial MRI prompted bilateral brain Hemispheric white matter,pons symmetry abnormal signal and left basal ganglia abnormal signal.The results of the genetic test showed that the GFM1 gene c.688G>A homozygous mutation(the parents are heterozygous carriers),this variant has been reported in compound heterozygous mutations case,while it is homozygous in our case,the patient was hospitalized for acidosis several times after respiratory infection.Conclusion: The age of onset of mitochondrial disease related to nuclear gene mutation is relatively early.The hepatocerebral type of mitochondrial DNA depletion syndrome with jaundice,abnormal liver function and coagulopathy is early onset,rapid progress and poor prognosis.Both of these two cases of mitochondrial diseases caused by nuclear gene mutations and lacked typical clinical manifestations.Performing genetic testing as early as possible can help to confirm the diagnosis and provide a basis for further prenatal diagnosis.At the same time,we reported DGUOK genes c.G396 A and c.T173 C as novel mutations,and firstly reported the GFM1 gene c.688G>A homozygous mutation case.