Pearson syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Pearson syndrome is a severe disorder that usually begins in infancy. It causes problems with the development of blood-forming (hematopoietic) cells in the bone marrow that have the potential to develop into different types of blood cells. For this reason, Pearson syndrome is considered a bone marrow failure disorder. Function of the pancreas and other organs can also be affected.

Most affected individuals have a shortage of red blood cells (anemia), which can cause pale skin (pallor), weakness, and fatigue. Some of these individuals also have low numbers of white blood cells (neutropenia) and platelets (thrombocytopenia). Neutropenia can lead to frequent infections; thrombocytopenia sometimes causes easy bruising and bleeding. When visualized under the microscope, bone marrow cells from affected individuals may appear abnormal. Often, early blood cells (hematopoietic precursors) have multiple fluid-filled pockets called vacuoles. In addition, red blood cells in the bone marrow can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment with certain dyes. These abnormal cells are called ring sideroblasts.

In people with Pearson syndrome, the pancreas does not work as well as usual. The pancreas produces and releases enzymes that aid in the digestion of fats and proteins. Reduced function of this organ can lead to high levels of fats in the liver (liver steatosis). The pancreas also releases insulin, which helps maintain correct levels of blood glucose, also called blood sugar. A small number of individuals with Pearson syndrome develop diabetes, a condition characterized by abnormally high blood glucose levels that can be caused by a shortage of insulin. In addition, affected individuals may have scarring (fibrosis) in the pancreas.

People with Pearson syndrome have a reduced ability to absorb nutrients from the diet (malabsorption), and most affected infants do not grow and gain weight at the expected rate (faltering weight). Another common occurrence in people with this condition is buildup in the body of a chemical called lactic acid (lactic acidosis), which can be life-threatening. In addition, liver and kidney problems can develop in people with this condition. Some people with Pearson syndrome have droopy eyelids (ptosis), vision problems, hearing loss, seizures, or movement disorders.

About half of children with this severe disorder die in infancy or early childhood due to severe lactic acidosis or liver failure. Many of those who survive develop signs and symptoms later in life of a related disorder called Kearns-Sayre syndrome. This condition causes weakness of muscles around the eyes and other problems.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Pearson syndrome is caused by defects in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA (mtDNA). This type of DNA contains many genes essential for normal mitochondrial function.

Pearson syndrome is caused by single, large deletions of mtDNA, which can range from 1,000 to 10,000 DNA building blocks (nucleotides). The most common deletion, which occurs in about 20 percent of affected individuals, removes 4,997 nucleotides. The mtDNA deletions involved in Pearson syndrome result in the loss of genes that provide instructions for proteins involved in oxidative phosphorylation. These deletions impair oxidative phosphorylation and decrease the energy available to cells.

It is not clear how loss of mtDNA leads to the specific signs and symptoms of Pearson syndrome, although the features of the condition are likely related to a lack of cellular energy.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Pearson syndrome is generally not inherited but arises from new (de novo) mutations that likely occur in early embryonic development.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Pearson syndrome is a rare condition; its prevalence is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of bone marrow cell morphology · Very frequent (99-80%)

An anomaly of the form or number of cells in the bone marrow.

Bone marrow hypocellularity · Very frequent (99-80%)

A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.

Decreased total neutrophil count · Very frequent (99-80%)

Abnormal decrease of absolute number of neutrophils in the blood, per microlitre, compared to a reference range for a given sex and age-group.

Elevated lactate:pyruvate ratio · Very frequent (99-80%)

An abnormal increase in the molar ratio of lactate to pyruvate in the blood circulation.

Hyperalaninemia · Very frequent (99-80%)

An increased concentration of alanine in the blood.

Lacticaciduria · Very frequent (99-80%)

An increased concentration of lactic acid in the urine.

Reticulocytosis · Very frequent (99-80%)

An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.

Severe infection · Very frequent (99-80%)

A type of infection that is regarded as a sign of a pathological susceptibility to infection because of unusual severity or intensity of the infection.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormal heart morphology (Frequent (79-30%)); Abnormality of the nervous system (Frequent (79-30%)); Anemia (Frequent (79-30%)); Cardiomyopathy (Frequent (79-30%)); Corneal stromal edema (Frequent (79-30%)); Exocrine pancreatic insufficiency (Frequent (79-30%)); Hepatomegaly (Frequent (79-30%)); Increased CSF lactate (Frequent (79-30%)); Increased circulating lactate concentration (Frequent (79-30%)); Postnatal growth retardation (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Pearson syndrome is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.