Pearson syndrome

Overview

Pearson syndrome is a rare and often fatal multisystem mitochondrial disorder that primarily affects infants and young children. First described in 1979 by Dr. Howard Pearson, the syndrome is characterized by sideroblastic anemia, pancreatic dysfunction, and other systemic manifestations due to defects in mitochondrial DNA (mtDNA). The condition impairs the function of cells that require high energy, such as those in the bone marrow, pancreas, liver, kidneys, and muscles. Pearson syndrome is part of a broader group of mitochondrial diseases and may evolve into other conditions, such as Kearns-Sayre syndrome, in survivors beyond infancy.

Causes

Pearson syndrome is caused by deletions or rearrangements in mitochondrial DNA, which impair the mitochondria's ability to produce energy through oxidative phosphorylation. Unlike nuclear DNA, mitochondrial DNA is inherited exclusively from the mother. Most cases of Pearson syndrome occur sporadically due to new (de novo) mutations and are not typically passed on from parents. These mtDNA mutations affect cells across multiple organs, leading to the multisystem nature of the disease.

Symptoms

The symptoms of Pearson syndrome often appear within the first few months of life and can vary depending on the extent and location of mitochondrial dysfunction. Common clinical features include:

• Sideroblastic anemia: A type of anemia characterized by the presence of ringed sideroblasts in the bone marrow and poor red blood cell production

• Neutropenia and thrombocytopenia: Low levels of white blood cells and platelets, leading to increased risk of infections and bleeding

• Exocrine pancreatic insufficiency: Poor digestion and malabsorption of nutrients due to insufficient pancreatic enzyme production

• Failure to thrive: Poor weight gain and growth in infancy

• Lactic acidosis: Elevated levels of lactic acid in the blood due to impaired energy metabolism

• Liver and kidney dysfunction: Including hepatomegaly (enlarged liver), renal tubular acidosis, and abnormal liver enzymes

• Neuromuscular symptoms: Hypotonia (low muscle tone), muscle weakness, and delayed motor development

Additional signs may include vomiting, diarrhea, hypoglycemia, and metabolic disturbances. In some cases, vision and hearing may also be affected.

Diagnosis

Diagnosing Pearson syndrome requires a combination of clinical evaluation, laboratory tests, and genetic studies. The diagnostic process typically includes:

• Complete blood count (CBC): To detect anemia, neutropenia, and thrombocytopenia

• Bone marrow biopsy: Reveals characteristic ringed sideroblasts and vacuolization of marrow precursors

• Pancreatic function tests: Assess levels of digestive enzymes and fat absorption

• Blood chemistry: To evaluate for lactic acidosis, liver dysfunction, and metabolic imbalances

• Mitochondrial DNA analysis: Detection of mtDNA deletions or rearrangements confirms the diagnosis

Due to the rarity and complexity of the disorder, referral to a specialist in mitochondrial diseases is often necessary for a definitive diagnosis and management plan.

Treatment

There is no cure for Pearson syndrome, and treatment is primarily supportive and aimed at managing symptoms and improving quality of life. Management strategies include:

• Blood transfusions: To treat anemia and maintain adequate red blood cell levels

• Pancreatic enzyme replacement therapy: To aid digestion and nutrient absorption

• Nutritional support: High-calorie diets, vitamin supplementation (especially B-vitamins and antioxidants), and feeding support may be necessary

• Management of infections: Prompt treatment with antibiotics and possible use of granulocyte colony-stimulating factor (G-CSF) for neutropenia

• Monitoring and treating metabolic disturbances: Including acidosis, electrolyte imbalances, and liver or renal dysfunction

• Developmental and physical therapy: For children with neuromuscular delays or motor difficulties

Due to the complexity of the condition, multidisciplinary care involving pediatricians, hematologists, gastroenterologists, geneticists, and metabolic specialists is essential.

Prognosis

The prognosis for Pearson syndrome is generally poor, with many affected children not surviving beyond infancy or early childhood due to severe metabolic complications, infections, or organ failure. However, in rare cases, children who survive the early years may show improvement in hematological symptoms but later develop Kearns-Sayre syndrome, a progressive mitochondrial disorder affecting the eyes, muscles, and heart. Early diagnosis, aggressive symptom management, and supportive care can extend survival and improve quality of life, but long-term outcomes remain guarded. Genetic counseling is recommended for families affected by Pearson syndrome to discuss recurrence risk and implications for future pregnancies.