Case Report: Clinical and Genetic Characteristics of Pearson Syndrome in a Chinese Boy and 139 Patients

Abstract

Background: Pearson’s syndrome (PS) is a rare multi-system disorder caused by mitochondrial DNA deletion. Most PS cases in the literature are individual reports, and there is a lack of systematic analysis of clinical features and gene mutations in large samples.Objective: To report a case of PS and summarize the clinical features and genetic characteristics of PS by reviewing the literature.Methods: We reported a case of PS in a boy with severe anemia and multi-system disorder. Genetic etiology was identified by mitochondrial DNA sequencing and whole-exon sequencing. Clinical features and gene mutations were summarized by literature review.Results: The patient had major clinical manifestations with recurrent anemia and multiple organ failure after infection. Mitochondrial DNA sequencing revealed a de novo heteroplasmic deletion of 3.063 kb (nt 6,224–9,287) with 75% heteroplasmy in peripheral blood. A total of 139 PS cases were retrieved after a literature search. The most common initial symptom was refractory anemia requiring repeated blood transfusion (86.2%), digestive system symptoms (26.9%), and failure to thrive (15.4%). During the course of disease, the observed symptoms were bone marrow failure (100%), metabolic disorders (61.87%) and gastrointestinal symptoms (61.87%), failure to thrive (48.9%), renal disorders (42.45%), and pancreatic exocrine insufficiency (39.6%). The mean heteroplasmy of mitochondrial DNA mutation in peripheral blood in deaths (76.29 ± 11.86%, n = 29) was higher than that in survivals (59.92 ± 23.87%, n = 26, p < 0.01). Among the patients with the 4.977 kb deletion, the heteroplasmy in peripheral blood in deaths (79.64 ± 9.71%, n = 11) was higher than that in survivals (56.67 ± 27.65%, n = 9, p < 0.05).Conclusion: PS can affect multiple systems, and mitochondrial DNA sequencing should be performed early. The heteroplasmy in peripheral blood is related to prognosis.

Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure

“…PMDs can affect virtually any tissue and organ, but typically, organs that are highly dependent on aerobic metabolism, such as muscle and brain are involved. PS is a clinically unique PMD, in which anemia is often the sole presenting symptom and other features suggesting PMD are lacking [ 3 , 6 , 31 ]. Other common initial symptoms are failure to thrive and gastrointestinal symptoms such as vomiting, diarrhea and feeding difficulties [ 7 , 31 ].…”

“…PS is a clinically unique PMD, in which anemia is often the sole presenting symptom and other features suggesting PMD are lacking [ 3 , 6 , 31 ]. Other common initial symptoms are failure to thrive and gastrointestinal symptoms such as vomiting, diarrhea and feeding difficulties [ 7 , 31 ]. In our recently published study on 25 individuals with PS, anemia developed at a median age of 5 months (range 0–31 months) [ 6 ].…”

“…Pregnancy and birth are usually uneventful [ 3 , 6 ]. However, about 10% of patients have intrauterine growth restriction [ 31 ]. Furthermore, Farruggia et al reported that 27% of newborns of PS are small for gestational age [ 3 ].…”

“…Patients with PS show macrocytic or normocytic hypogenerative anemia [ 3 , 6 , 31 ]. Majority of patients have neutropenia and thrombocytopenia as well [ 3 – 6 , 32 ].…”

“…Various non-hematological complications generally develop during the course in patients with PS and are generally irreversible. Figure 4 displays complications observed in 25 patients with PS included in our previous retrospective study [ 6 ], Table 1 summarizes the incidences and the age at onset for major complications in a most recent review of 139 cases of PS by Ying et al and 3 largest cohorts of PS in the literatures [ 5 – 7 , 31 ]. The majority of patients suffer from failure to thrive resulting in growth retardation and small stature [ 3 – 7 , 31 ].…”