Pearson syndrome

Pearson syndrome is a mitochondrial disorder that predominantly affects multiple organ systems, most the bone marrow and exocrine pancreas. It is characterized by refractory sideroblastic anemia, vacuolization of bone marrow precursors, and pancreatic dysfunction. This very rare condition, affecting fewer than 1 in 1 million people, typically presents in early life with a range of metabolic, hematologic, and gastrointestinal complications. The clinical features vary considerably between individuals, making each case unique.

The clinical presentation of Pearson syndrome is multisystem and complex. Hematologic abnormalities manifest as hypoplastic anemia, reticulocytopenia, thrombocytopenia, and pancytopenia, while metabolic disturbances include complex organic aciduria, metabolic acidosis, and 3-methylglutaric aciduria. In addition, nearly all affected individuals experience type I diabetes mellitus, renal Fanconi syndrome, and are small for gestational age. Gastrointestinal and pancreatic involvement is evident through chronic diarrhea, steatorrhea, exocrine pancreatic insufficiency, and, in some cases, pancreatic fibrosis. Other common features include failure to thrive, dehydration, hepatomegaly, and lactic acidosis. That not all individuals experience every symptom and that severity and onset can differ widely.

Pearson syndrome is a mitochondrial disorder, and its inheritance follows a maternal pattern. Because mitochondria are passed exclusively from the mother, all children of an affected mother inherit the mitochondrial DNA, although the extent to which symptoms develop can vary due to heteroplasmy, where different cells contain varying proportions of mutated mitochondria. The precise genetic basis of Pearson syndrome remains under investigation; however, its mitochondrial inheritance underscores the importance of genetic counseling for family planning and the assessment of recurrence risk.

Currently, management of Pearson syndrome focuses on supportive care and symptom management, as there are no treatments that specifically target the underlying cause. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the range of complications including hematologic, metabolic, and gastrointestinal issues. Regular surveillance is an essential part of long-term care, as ongoing monitoring can help detect complications early, particularly through routine evaluations of blood counts, metabolic panels, and pancreatic function. Families are encouraged to work closely with specialists and to consider genetic counseling as part of their management strategy.

The long-term outlook for people with Pearson syndrome varies, with life expectancy ranging from several years to multiple decades depending on the severity of organ involvement and access to comprehensive care. With modern, multidisciplinary management and regular monitoring, many individuals experience improvements in their quality of life despite the disorder's complex nature. Outcomes described in medical literature continue to evolve as standards of care improve. Families should consider consulting specialists and a genetic counselor to better understand treatment options and implications for family planning, and they may also benefit from connecting with support groups for additional guidance and assistance.

Clinical trials are underway exploring new treatment approaches for Pearson syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.