PEARSON SYNDROME: MULTISYSTEM MITOCHONDRIAL DISORDER WITH BONE MARROW FAILURE
Author(s): ,
Ayami Yoshimi
Affiliations:
Department of Pediatrics and Adolescent Medicine,UNIVERSITY OF FREIBURG,Freiburg,Germany
,
Sarah Grünert
Affiliations:
Department of Pediatrics and Adolescent Medicine,UNIVERSITY OF FREIBURG,Freiburg,Germany
,
Michaela Kuhlen
Affiliations:
Center for Child and Adolescent Health,Heinrich Heine University,Duesseldorf,Germany
,
Arndt Borkhardt
Affiliations:
Center for Child and Adolescent Health,Heinrich Heine University,Duesseldorf,Germany
,
Kyogo Suzuki
Affiliations:
Department of Pediatrics,Nagoya University Graduate School of Medicine,Nagoya,Japan
,
Udo Kontny
Affiliations:
Department of Hematology, Oncology and Stem Cell Transplantation,RWTH Aachen University Medical School,Aachen,Germany
,
Stefan Bielack
Affiliations:
Pediatrics 5 (Oncology, Hematology, Immunology),Klinikum Stuttgart—Olgahospital,Stuttgart,Germany
,
Holger Cario
Affiliations:
Department of Pediatrics and Adolescent Medicine,University Medical Center Ulm,Ulm,Germany
Charlotte Niemeyer
Affiliations:
Department of Pediatrics and Adolescent Medicine,UNIVERSITY OF FREIBURG,Freiburg,Germany
EHA Library. Yoshimi A. 06/13/15; 100770; P629 Disclosure(s): UNIVERSITY OF FREIBURG
Department of Pediatrics and Adolescent Medicine
Ayami Yoshimi
Ayami Yoshimi
Contributions
Abstract
Abstract: P629

Type: Poster Presentation

Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

Location: Poster area (Hall C)

Background
Pearson syndrome (PS) was originally reported as a fatal disease in infancy characterized by sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreas dysfunction. In addition, involvement of multiple other organs and subsequent development of Kearns-Sayre Syndrome (KSS) have  also been reported. Both PS and KSS are associated with single mitochondrial DNA (mtDNA) deletions. There are few systematic studies on PS because of its rarity.

Aims
To characterize the clinical and hematological presentations and courses of patients with PS.




Methods
We retrospectively reviewed clinical and laboratory data of 20 patients (12 M/ 8 F) with PS diagnosed between 1987 and 2012 in Germany. 

Results
The median hemoglobin level was 5.9 g/dl (2.2-9.8 g/dl) and the mean corpuscular volume of red cells (MCV) was elevated or normal in 12 and 14 patients, respectively (unknown in 4). Some patients had normal neutrophil and platelet counts at diagnosis (n=5/6), but all of them developed bi- or pancytopenia later. The hemoglobin F level was elevated for age in 8 of 9 patients examined. Bone marrow was normo- and hypocellular in 13 and 7 patients, respectively. All patients had vacuolization of erythroid and myeloid precursors, but ringed sideroblasts are only observed in 13 of 19 patients examined. Serum lactate was elevated in 14 of 15 patients studied. The diagnosis of PS could be confirmed by the detection of mtDNA deletion in all patients.
The median age at the time of the last follow-up was 39 months (6 months to 14 years). Hematological recovery was observed in most patients with a longer follow-up time. Ten patients became transfusion independent at a median age of 27 months (11 to 67 months), while one patient was still transfusion dependent when he died at the age of 8 years. Various symptoms and organ dysfunctions developed during clinical courses, including failure to thrive/short stature (n=8, median age of presentation: 26 months (m)), liver dysfunction (n=2, 21 m), renal tubulopathy/Fanconi syndrome (n=5, 32 m), pancreas insufficiency (n=6, 13 m), cardiac disease (n=3, 45 m), diabetes (n=1, 19 m), other endocrine dysfunctions (n=4, 63 m), hearing loss (n=1, 115 m), ophthalmoplegia (n=1, 19 m), retinitis pigmentosa (n=1, 92 m), cataract (n=1, 39 m), muscle hypotonia (n=4, 31 m), ataxia (n=2, 54 m) and encephalopathy (n=1, 74 m). Seven patients died of acute metabolic acidosis with other complications at the median age of 49 months (14-101 months). The longest survivor (death at 14 years of age) suffered from KSS-like disease. 

Summary
These findings suggest that PS is a multisystem mitochondrial disorder in infancy with bone marrow failure as the main presenting feature. Because patients can initially present with only anemia, clinicians should consider PS as a differential diagnosis of hypoproliferative anemia in early childhood. Although hematological improvement can be expected in long survivors, patients have highly heterogeneous clinical courses with varied extents of multi-organ involvement. Therefore, intensive monitoring and managing of multisystem complications are crucial.  

Keyword(s): Anemia, Bone marrow failure, Mitochondria

Session topic: BMF syndromes incl. PNH - Clinical
Abstract: P629

Type: Poster Presentation

Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

Location: Poster area (Hall C)

Background
Pearson syndrome (PS) was originally reported as a fatal disease in infancy characterized by sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreas dysfunction. In addition, involvement of multiple other organs and subsequent development of Kearns-Sayre Syndrome (KSS) have  also been reported. Both PS and KSS are associated with single mitochondrial DNA (mtDNA) deletions. There are few systematic studies on PS because of its rarity.

Aims
To characterize the clinical and hematological presentations and courses of patients with PS.




Methods
We retrospectively reviewed clinical and laboratory data of 20 patients (12 M/ 8 F) with PS diagnosed between 1987 and 2012 in Germany. 

Results
The median hemoglobin level was 5.9 g/dl (2.2-9.8 g/dl) and the mean corpuscular volume of red cells (MCV) was elevated or normal in 12 and 14 patients, respectively (unknown in 4). Some patients had normal neutrophil and platelet counts at diagnosis (n=5/6), but all of them developed bi- or pancytopenia later. The hemoglobin F level was elevated for age in 8 of 9 patients examined. Bone marrow was normo- and hypocellular in 13 and 7 patients, respectively. All patients had vacuolization of erythroid and myeloid precursors, but ringed sideroblasts are only observed in 13 of 19 patients examined. Serum lactate was elevated in 14 of 15 patients studied. The diagnosis of PS could be confirmed by the detection of mtDNA deletion in all patients.
The median age at the time of the last follow-up was 39 months (6 months to 14 years). Hematological recovery was observed in most patients with a longer follow-up time. Ten patients became transfusion independent at a median age of 27 months (11 to 67 months), while one patient was still transfusion dependent when he died at the age of 8 years. Various symptoms and organ dysfunctions developed during clinical courses, including failure to thrive/short stature (n=8, median age of presentation: 26 months (m)), liver dysfunction (n=2, 21 m), renal tubulopathy/Fanconi syndrome (n=5, 32 m), pancreas insufficiency (n=6, 13 m), cardiac disease (n=3, 45 m), diabetes (n=1, 19 m), other endocrine dysfunctions (n=4, 63 m), hearing loss (n=1, 115 m), ophthalmoplegia (n=1, 19 m), retinitis pigmentosa (n=1, 92 m), cataract (n=1, 39 m), muscle hypotonia (n=4, 31 m), ataxia (n=2, 54 m) and encephalopathy (n=1, 74 m). Seven patients died of acute metabolic acidosis with other complications at the median age of 49 months (14-101 months). The longest survivor (death at 14 years of age) suffered from KSS-like disease. 

Summary
These findings suggest that PS is a multisystem mitochondrial disorder in infancy with bone marrow failure as the main presenting feature. Because patients can initially present with only anemia, clinicians should consider PS as a differential diagnosis of hypoproliferative anemia in early childhood. Although hematological improvement can be expected in long survivors, patients have highly heterogeneous clinical courses with varied extents of multi-organ involvement. Therefore, intensive monitoring and managing of multisystem complications are crucial.  

Keyword(s): Anemia, Bone marrow failure, Mitochondria

Session topic: BMF syndromes incl. PNH - Clinical

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