Clinical And Genetic Features Of Pearson Syndrome:A Case Report And Literature Review

Objective Pearson syndrome(PS),also known as bone marrow-pancreas syndrome,is a rare sporadic syndrome caused by large-scale deletion or duplication of mitochondrial DNA(mtDNA).This paper aimed to explore the clinical and genetic characteristics of a pediatric patient with PS diagnosed by genetic analysis.Following that,systematic literature review was conducted to provide references for subsequent diagnostic and therapeutic study of this condition.Methods The clinical symptoms,signs and laboratory data of the patient were collected and analyzed.Meanwhile,genetic analysis was performed on the patients and their family members to explore the genetic etiology.By way of retrieving Pubmed,CNKI,Wanfang and VIP Database for Chinese Technical Periodicals and other medical literature databases,a systematic literature review was conducted on all reported PS cases from January 1979 to December 2018.Results The child was a 13-month-old male patient,who was referred to our clinic with the complaint of anemia,abnormal liver function and hyperlactacidemia discovered over 1 year.When aged 6 months,the baby underwent Whole Exome Sequencing(WES)analysis but no genetic cause was identified.Physical examination at referral revealed growth retardation of the body weight and length,many Mongolia spots in the dorsal skin and a palpable liver 3 cm below the right subcostal margin with medium texture.The spleen was not enlarged.On biochemistry analysis,the plasma levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bile acids(TBA),gamma-glutamyl transpeptidase(GGT)and lactic acid were all elevated.The count of red blood cells,platelets and hemoglobin were all decreased.Multiplex ligation-dependent probe amplification(MLPA)assay detected a large mtDNA deletion,and further high-throughput sequencing of mitochondrial genome revealed a mtDNA deletion of 4734 bp in size from nucleotide 11220 to 15953,which was not detected in his parents and elder brother.On a follow-up at the age of 14 months,he still had growth retardation and mild anemia,and the levels of ALT,AST,TBA,and lactic acid were still elevated.A total of 146 literatures on PS were collected,involving 98 PS patients,among whom 68 had intact clinical data while negative gender or racial difference.The mtDNA variants detected in the PS patients were all deletions ranging from 2.5kb to 9.2kb,with m.8483_m.13459del4977 as the most common variant,accounting for 14%(8/57)of all the mtDNA variants.Among the 68 patients with PS,98.53%(67/68)had anemia as the initial presentation,and 92%(46/50)exhibited characteristic vacuolization of hematopoietic precursors on examination of bone marrow smear.Chronic steatorrhea,malabsorption and growth retardation caused by pancreatic exocrine insufficiency were observed in 77.5%(31/40)of the patients.And 89.29%(25/28)of them had neurologic and muscular system impairment.In addition,other organs or systems could also be affected to varying degrees.According to the preliminary statistics,48.48%(32/66)of the patients died of various complications with poor prognosis.Conclusions Anemia,thrombocytopenia,hyperlactic acidemia,liver function damage and cholestasis were the prominent manifestations in the pediatric PS patient.The 4734 bp deletion in mtDNA was reported for the first time,constituting a genetic evidence for the definite diagnosis and genetic counseling of the affected family.The patient demonstrated stable condition when aged 14 months,but the long-term prognosis remained to be observed.As a result of literature review,mtDNA variants detected in the PS patients were all deletions of different size.Most PS patients had anemia as the initial presentation,and pancreatic exocrine dysfunction were rather common in such patients.Moreover,renal,muscular and neural impairment could occur.Due to the lack of specific treatment,PS patients usually had poor long-term prognosis.These findings enriched the variant spectrum of mtDNA,and were significant for the subsequent diagnosis and management of PS patients.