Case Study: Infantile Pearson Marrow-Pancreas Syndrome Presenting as Isolated Transfusion-Dependent Cytopenias with Subsequent Fatal Pulmonary Infection
Dr. Reem Ahmad Alrefai 1, Dr. Hussam Abu Farsakh MD *2
2. First Medical Lab Amman, Jordan.
*Correspondence to: Dr. Hussam Abu Farsakh, First Medical Lab Amman, Jordan.
Copyright.
© 2026 Dr. Hussam Abu Farsakh, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 06 August 2026
Published: 01 September 2026
DOI: https://doi.org/10.5281/zenodo.22224907
Abstract
Pearson Marrow-Pancreas Syndrome (PMPS) is a rare, severe mitochondrial disease characterized by vacuolization of bone marrow precursors, sideroblastic anemia, and exocrine pancreatic dysfunction. However, heterogeneous clinical presentations can complicate early recognition. We report the case of a 14-month-old female presenting with profound macrocytic anemia, transfusion dependency, and multi-lineage marrow dysplasia with characteristic non-lipid, non-glycogen cytoplasmic vacuolation, but notably lacking clinical exocrine pancreatic involvement. Fetal hemoglobin (HbF) was markedly elevated at 29.1%. Despite bone marrow confirmation of PMPS, the patient experienced a rapid fatal course, succumbing to fulminant pneumonia four months after diagnosis at 18 months of age. This case underscores the variable phenotypic presentation of PMPS in early childhood and highlights the critical vulnerability of affected infants to life-threatening infections even prior to the onset of multisystem organ failure.
Keywords: Mitochondrial disorders, sideroblastic anemia, genetic screening anemia.
Introduction
Pearson marrow-pancreas syndrome is a rare multisystem mitochondrial disorder caused by large-scale deletions of mitochondrial DNA.[1-3] It typically presents in infancy and is characterized by bone marrow failure with transfusion-dependent sideroblastic anemia.[1,2] Bone marrow is particularly characteristic for vacuolization of erythroid and myeloid and ring sideroblasts on iron staining with abnormal erythropoiesis.[1,4] In addition to its hematologic manifestations, Pearson-Pancreas syndrome classically involves pancreatic exocrine dysfunction, hence the name, which manifests as chronic diarrhea, steatorrhea, failure to thrive, malnutrition, and deficiencies of fat-soluble vitamins.[1,2] Other organ systems, including the liver, kidneys, heart, and endocrine system, may also be affected, reflecting the multisystem nature of this mitochondrial disease.[2,3]
In this report, we describe a 14-month-old female who presented with severe refractory macrocytic anemia requiring multiple packed red blood cell (pRBC) transfusions. This case illustrates the phenotypic variability of Pearson syndrome, as the patient did not exhibit the typical clinical features of exocrine pancreatic insufficiency.
Case Presentation
The patient was a 14-month-old female who presented for further evaluation of severe, transfusion-dependent anemia diagnosed in early infancy. Her clinical course was characterized by progressive pallor, fatigue, and poor somatic growth, requiring regular pRBC transfusions every 3–4 weeks. Notably, there was no convincing clinical evidence of exocrine pancreatic dysfunction throughout her early development or at the time of presentation. Stool frequency and consistency were normal, with no history of steatorrhea or abdominal distension. The family history was non-contributory; her parents were non-consanguineous, with no known history of inherited hematologic, metabolic, or mitochondrial disorders on either side of the family.
On admission, the patient was hemodynamically stable, with a heart rate of 124 beats/min, respiratory rate of 28 breaths/min, and blood pressure of 88/54 mmHg.
Growth parameters: Severe growth impairment was noted, with both weight and length below the 3rd percentile for age.
General appearance: The patient appeared pale with evident failure to thrive. Marked cutaneous and mucosal pallor was noted, with no apparent facial dysmorphism or cranial abnormalities.
Cardiovascular examination: A soft grade II/VI systolic ejection murmur was audible at the upper left sternal border, likely reflecting a hyperdynamic circulation associated with chronic anemia.
Abdominal examination: The abdomen was soft and non-tender. Mild hepatomegaly was present, with the liver edge palpable 1.5–2 cm below the right costal margin. No splenomegaly was detected.
Neuromuscular examination: Mild generalized hypotonia was noted, accompanied by developmental delay, with gross motor skills corresponding approximately to an 8–9-month developmental level. Extraocular movements were intact, with no ptosis or ophthalmoplegia.
Bone marrow Iron stain using Prussian Blue Stain revealed ringed sideroblasts and increased iron deposition in macrophages. Where the Marrow smear showed dysplastic features of megakaryocytes with some vacuolated forms. The vacuoles are PAS and Sudan Black III negative with dysmyelopoiesis, dyserythropoiesis with a Myeloid: Erythroid ration of 2:1. Core biopsy showing 50% cellularity. The findings are consistent of Pearson Disease
Key diagnostic highlights:
Clinical Outcome and follow-up:
Following diagnostic confirmation of Pearson Marrow-Pancreas Syndrome based on pathognomonic marrow morphology and clinical features, the patient was maintained on a supportive care regimen including frequent pRBC transfusions and close clinical surveillance.
At 18 months of age, four months after the diagnosis, the patient presented with acute, severe respiratory distress secondary to fulminant pneumonia. Despite aggressive resuscitation and broad-spectrum antimicrobial and supportive measures, the patient rapidly deteriorated due to acute respiratory failure superimposed on underlying mitochondrial disease and neutropenia, and subsequently passed away.
Discussion
Pearson syndrome is a rare mitochondrial disorder caused by large-scale deletions of mitochondrial DNA (mtDNA), typically presenting in infancy with sideroblastic anemia, bone marrow vacuolization, and exocrine pancreatic dysfunction.[5-7] However, its clinical presentation is highly variable, and pancreatic manifestations may be absent or clinically unapparent during infancy, as demonstrated in our patient.[5,7-9] The combination of macrocytic anemia, severe reticulocytopenia, neutropenia, elevated HbF, and characteristic bone marrow abnormalities should raise suspicion for Pearson syndrome even in the absence of gastrointestinal symptoms.[6,8] Nevertheless, these findings are not specific and may overlap with other inherited or acquired disorders, making molecular genetic testing essential for diagnostic confirmation.[6,8,10] Early recognition is important because affected infants are at risk of severe anemia, neutropenia, metabolic decompensation, and infectious complications, while survivors may develop features associated with Kearns–Sayre syndrome later in life.[6,7,11]
Conclusion
This case highlights the phenotypic variability of Pearson syndrome and demonstrates that the absence of clinically apparent exocrine pancreatic dysfunction does not exclude the diagnosis, particularly during infancy. In infants with unexplained transfusion-dependent sideroblastic anemia and characteristic bone marrow abnormalities, Pearson syndrome should remain an important diagnostic consideration, with molecular genetic testing used to confirm the diagnosis.
Human Ethics:
Consent was obtained or waived by all participants in this study.
Reference