Pearson Marrow-Pancreas Syndrome

Overview

Pearson marrow-pancreas syndrome is a rare and severe mitochondrial disorder that primarily affects the bone marrow and pancreas, often beginning in infancy. It is caused by deletions in mitochondrial DNA, leading to impaired energy production in cells.

Pearson marrow-pancreas syndrome should be suspected in infants or young children presenting with unexplained bone marrow failure and pancreatic insufficiency, especially when accompanied by lactic acidosis or multisystem involvement**.

Cause and Genetics

• Etiology: Large deletions in mitochondrial DNA (mtDNA), commonly a 4,997-base pair deletion
• Inheritance: Typically de novo (not inherited)
• Pathophysiology: Impaired oxidative phosphorylation, especially in high-energy-demand tissues

Bone Marrow Involvement

• Bone marrow failure: anemia, neutropenia, thrombocytopenia
• Ring sideroblasts: iron-loaded mitochondria in red blood cells
• Vacuolated precursors: immature blood cells with fluid-filled vacuoles

Pancreatic and Systemic Effects

• Exocrine pancreatic insufficiency: poor digestion of fats and proteins
• Endocrine dysfunction: possible diabetes mellitus
• Malabsorption and failure to thrive
• Lactic acidosis: due to mitochondrial dysfunction
• Possible involvement of liver, kidneys, heart, and eyes

Neurological and Later Manifestations

Survivors may develop Kearns-Sayre syndrome, which includes:

• Progressive external ophthalmoplegia
• Retinal degeneration
• Cardiac conduction defects

Diagnosis

• Bone marrow biopsy: vacuolated precursors, ring sideroblasts
• Genetic testing: confirms mtDNA deletions
• Blood tests: cytopenias, lactic acidosis

Clinical Pearl: If an infant presents with macrocytic anemia, pancreatic insufficiency, and lactic acidosis, Pearson syndrome should be high on the differential — especially if bone marrow findings are atypical and multisystem signs are present.

Management

• Supportive care only (no cure)
• Blood transfusions for anemia
• Pancreatic enzyme replacement
• Nutritional support and vitamin supplementation (e.g., CoQ10, L-carnitine)
• Multidisciplinary care: hematology, endocrinology, gastroenterology, neurology

Prognosis

Prognosis is generally poor. Many affected children die in infancy or early childhood due to lactic acidosis or organ failure. Survivors may develop progressive mitochondrial disease features later in life.

**Key Clinical Findings That Raise Suspicion