1 - Unidade de Doenças Metabólicas, Hospital Dona Estefânia - CHULC, Lisboa, Portugal;
1 - Unidade de Doenças Metabólicas, Área de Pediatria Médica,, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
2 - Unidade de Rastreio Neonatal, Metabolismo & Genética, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal;
3 - Unidade de Hematologia Pediátrica, Área de Pediatria Médica, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
4 - Serviço de Neonatologia, Maternidade Dr. Alfredo da Costa, Área de Pediatria Médica, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
- Poster no 17th International Symposium da Sociedade Portuguesa de Doenças Metabólicas, Fátima, 8 a 10 de setembro de 2021 (Prémio de Melhor Poster)
Resumo:
Background: Pearson syndrome (PS) is a rare, multi-systemic disorder, caused by large-scale deletions or duplications of mitochondrial DNA. PS manifests typically in infancy with bone marrow failure, sideroblastic anemia and variable exocrine pancreatic insufficiency. Failure to thrive, lactic acidosis or tubulopathy are common additional findings. The mortality rate is significant in early childhood – those who survive may evolve into the KearnsSayre Syndrome spectrum. With this case series we aim to illustrate the phenotypic spectrum of PS.
PATIENTS 1&2: Male, monochorionic diamniotic twins presented with severe fetal anemia and intrauterine growth restriction. Born at 31 weeks, they evolved with severe pancytopenia, lactic acidosis, tubulopathy, hyperammonemia and left ventricular hypertrophy with lethal outcome – at 27 and 33 days of age – despite transfusional support, bicarbonate, carnitine and filgrastim. A large deletion in leukocyte mtDNA confirmed PS.
PATIENT 3: Male, 11 months old, presented with failure to thrive, recurrent infections, pancytopenia with macrocytosis and persistent hyperlactacidemia. Bone marrow examination showed vacuolized hematopoietic precursors and ringed sideroblasts. Further metabolic study revealed mitochondrial dysfunction and transient low fecal elastase. A large deletion in leukocyte mtDNA confirmed PS. He required multiple admissions for severe infection and metabolic decompensation. At 3 years old he has normal psychomotor development and requires nutritional supplementation and sporadic transfusional support.
PATIENT 4: Female, 15 months old, presented with failure to thrive, feeding difficulties and fatigue. Pancytopenia with severe macrocytic anemia, hyperlactacidemia and persistent low fecal elastase were present in subsequent evaluations. Bone marrow examination revealed vacuolized precursors and a large deletion of mtDNA in leucocytes confirmed PS. At 20 months of age, she has normal growth and psychomotor development and requires regular transfusional support, pancreatic enzyme and nutritional supplementation.
COMMENTS: This case series illustrates the clinical variability of PS. Aplastic anemia and hyperlactacidemia were present in all cases and thus should raise suspicion for PS, especially if exocrine pancreatic or renal tubular dysfunction are present. Follow-up of patients will be needed to evaluate a possible progression into the Kearns-Sayre spectrum or improvement of hematologic manifestations.