Pearson syndrome is an infantile single large-scale mitochondrial DNA deletion syndrome. The primary lesion is a heteroplasmic mtDNA deletion, often the common 4.97 kb deletion but variable in size and position, that removes mitochondrial coding and transfer-RNA sequence needed for respiratory-chain oxidative phosphorylation. A high deleted-mtDNA burden in hematopoietic and other proliferative tissues produces transfusion-dependent sideroblastic anemia, pancytopenia with vacuolated marrow precursors, exocrine pancreatic dysfunction, poor growth, renal tubular disease, lactic acidosis, and early childhood multisystem risk. Survivors can later evolve toward a Kearns-Sayre-like phenotype as deleted mtDNA becomes clinically important in post-mitotic tissues. Pearson syndrome is therefore modeled as a distinct disorder entry, not as a subtype of Kearns-Sayre syndrome, while both entries are grouped under single large-scale mtDNA deletion disorders.
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name: Pearson syndrome
creation_date: "2026-07-06T01:07:38Z"
category: Mendelian
synonyms:
- Pearson marrow-pancreas syndrome
- Pearson's marrow/pancreas syndrome
- Pearson's syndrome
description: >-
Pearson syndrome is an infantile single large-scale mitochondrial DNA deletion
syndrome. The primary lesion is a heteroplasmic mtDNA deletion, often the
common 4.97 kb deletion but variable in size and position, that removes
mitochondrial coding and transfer-RNA sequence needed for respiratory-chain
oxidative phosphorylation. A high deleted-mtDNA burden in hematopoietic and
other proliferative tissues produces transfusion-dependent sideroblastic
anemia, pancytopenia with vacuolated marrow precursors, exocrine pancreatic
dysfunction, poor growth, renal tubular disease, lactic acidosis, and early
childhood multisystem risk. Survivors can later evolve toward a
Kearns-Sayre-like phenotype as deleted mtDNA becomes clinically important in
post-mitotic tissues. Pearson syndrome is therefore modeled as a distinct
disorder entry, not as a subtype of Kearns-Sayre syndrome, while both entries
are grouped under single large-scale mtDNA deletion disorders.
references:
- reference: PMID:20301382
title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
tags:
- GeneReviews
- reference: PMID:36253820
title: "Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure."
- reference: PMID:7581370
title: Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas syndrome.
disease_term:
preferred_term: Pearson syndrome
term:
id: MONDO:0010797
label: Pearson syndrome
parents:
- mitochondrial disease
- inborn error of metabolism
mappings:
mondo_mappings:
- term:
id: MONDO:0010797
label: Pearson syndrome
mapping_predicate: skos:exactMatch
mapping_source: MONDO
mapping_justification: Primary MONDO disease identifier for this Pearson syndrome entry.
external_assertions:
- name: OMIM Pearson syndrome record
source: OMIM
assertion_type: disease_record
external_id: OMIM:557000
url: https://omim.org/entry/557000
description: OMIM phenotype record for Pearson syndrome.
- name: Orphanet Pearson syndrome record
source: Orphanet
assertion_type: structured_disease_record
external_id: ORPHA:699
url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=699
description: Orphanet structured disease record for Pearson syndrome.
classifications:
icimd_category:
- classification_value: single_large_scale_mtdna_deletions
notes: >-
WP-015 seed 6.3.01.01. Pearson syndrome is one of the ICIMD disorders
associated with single large-scale mtDNA deletions.
inheritance:
- name: Usually de novo mitochondrial inheritance
description: >-
Pearson syndrome is part of the single large-scale mitochondrial DNA deletion
syndrome spectrum. Most cases are de novo, while rare maternal transmission
is possible because mitochondrial DNA is maternally inherited.
inheritance_term:
preferred_term: Mitochondrial inheritance
term:
id: HP:0001427
label: Mitochondrial inheritance
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
SLSMDSs are almost never inherited, suggesting that these disorders are
typically caused by a de novo single large-scale mitochondrial DNA
explanation: GeneReviews describes the SLSMD inheritance pattern as usually de novo.
- reference: PMID:36253820
reference_title: "Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure."
supports: SUPPORT
evidence_source: OTHER
snippet: mtDNA is inherited exclusively from the mother
explanation: Pearson syndrome review notes the maternal inheritance route for mtDNA when transmission occurs.
pathophysiology:
- name: Single Large-Scale mtDNA Deletion
description: >-
Pearson syndrome is caused by a single large-scale mitochondrial DNA
deletion. The deleted molecule is heteroplasmic and can be present at high
load in blood and marrow early in life; deletion size and breakpoints vary,
so the disease is not tied to a single nuclear gene or enzyme defect.
role: trigger
biological_processes:
- preferred_term: mitochondrial DNA metabolic process
term:
id: GO:0032042
label: mitochondrial DNA metabolic process
modifier: ABNORMAL
evidence:
- reference: PMID:36253820
reference_title: "Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure."
supports: SUPPORT
evidence_source: OTHER
snippet: large-scale mitochondrial DNA deletions (SLSMDs).
explanation: The review identifies single large-scale mtDNA deletions as the causal lesion of Pearson syndrome.
- reference: PMID:7581370
reference_title: Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: describe mitochondrial DNA deletions as consistent features in this syndrome.
explanation: This 21-case series supports mtDNA deletions as consistent molecular features of Pearson syndrome.
downstream:
- target: Mitochondrial Translation and OXPHOS Deficiency
causal_link_type: DIRECT
description: >-
Deletion of mtDNA-encoded respiratory-chain and tRNA sequence reduces the
supply of mitochondrial translation products needed for oxidative
phosphorylation.
- name: Mitochondrial Translation and OXPHOS Deficiency
conforms_to: "mitochondrial_dysfunction#Bioenergetic Decline and Oxidative Stress"
description: >-
Deleted mtDNA compromises mitochondrial protein synthesis and respiratory
chain oxidative phosphorylation. The pathway product state is reduced
oxidative ATP production with compensatory lactate accumulation, especially
in tissues where the deleted mtDNA load exceeds the bioenergetic threshold.
role: central_effector
biological_processes:
- preferred_term: mitochondrial translation
term:
id: GO:0032543
label: mitochondrial translation
modifier: DECREASED
- preferred_term: oxidative phosphorylation
term:
id: GO:0006119
label: oxidative phosphorylation
modifier: DECREASED
- preferred_term: aerobic respiration
term:
id: GO:0009060
label: aerobic respiration
modifier: DECREASED
chemical_entities:
- preferred_term: ATP
term:
id: CHEBI:15422
label: ATP
modifier: DECREASED
- preferred_term: (S)-lactate
term:
id: CHEBI:16651
label: (S)-lactate
modifier: INCREASED
evidence:
- reference: PMID:7581370
reference_title: Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: phosphorylation associated with deletions of the mitochondrial DNA.
explanation: >-
The Pearson series directly links mtDNA deletions to an oxidative
phosphorylation defect.
downstream:
- target: Bone Marrow Failure and Sideroblastic Anemia
causal_link_type: DIRECT
description: >-
Hematopoietic precursors with high deleted-mtDNA burden cannot meet
energy and heme-synthesis demands, producing marrow failure.
- target: Exocrine Pancreatic and Multisystem Energy Failure
causal_link_type: DIRECT
description: >-
Bioenergetic failure in pancreas, kidney, muscle, liver, and other
tissues produces the non-hematologic Pearson phenotype.
- name: Bone Marrow Failure and Sideroblastic Anemia
description: >-
High deleted-mtDNA burden in hematopoietic cells produces infantile
hyporegenerative marrow failure. The characteristic clinical readout is
transfusion-dependent sideroblastic anemia with variable neutropenia and
thrombocytopenia; marrow cytology can show vacuolated erythroid and myeloid
precursors with ring sideroblasts.
role: consequence
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: transfusion-dependent sideroblastic anemia with variable cell line involvement),
explanation: GeneReviews summarizes the hematologic Pearson phenotype.
- reference: PMID:7794775
reference_title: "Pearson's marrow/pancreas syndrome: haematological features associated with deletion and duplication of mitochondrial DNA."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: sideroblastic anaemia, vacuolization of bone marrow precursors, and neutropenia.
explanation: This case report links mtDNA rearrangement with the diagnostic marrow phenotype.
downstream:
- target: Sideroblastic anemia
causal_link_type: DIRECT
- target: Pancytopenia
causal_link_type: DIRECT
- name: Exocrine Pancreatic and Multisystem Energy Failure
description: >-
The same respiratory-chain deficit extends beyond marrow to exocrine
pancreas, kidney, muscle, liver, and cardiac tissue. This produces poor
weight gain, exocrine pancreatic insufficiency, renal tubular acidosis,
hypotonia, cardiac dysfunction, and lactic acidosis; surviving children may
later manifest Kearns-Sayre-like ophthalmoplegia and neuromuscular disease.
role: consequence
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: exocrine pancreatic dysfunction, poor weight gain, and lactic acidosis.
explanation: GeneReviews summarizes core non-hematologic Pearson manifestations.
- reference: PMID:36253820
reference_title: "Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure."
supports: SUPPORT
evidence_source: OTHER
snippet: failure to thrive, muscle hypotonia, exocrine pancreas insufficiency, renal tubulopathy
explanation: The recent review documents multisystem non-hematologic Pearson complications.
- reference: PMID:36253820
reference_title: "Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure."
supports: SUPPORT
evidence_source: OTHER
snippet: experience a phenotypical change to Kearns-Sayre syndrome.
explanation: The review supports later evolution from Pearson syndrome toward Kearns-Sayre syndrome in some survivors.
phenotypes:
- name: Sideroblastic anemia
category: Hematologic
description: Infantile refractory or transfusion-dependent sideroblastic anemia.
phenotype_term:
preferred_term: Sideroblastic anemia
term:
id: HP:0001924
label: Sideroblastic anemia
evidence:
- reference: PMID:29337599
reference_title: Pearson syndrome.
supports: SUPPORT
evidence_source: OTHER
snippet: characterized by refractory sideroblastic anemia during infancy.
explanation: Review abstract identifies sideroblastic anemia as the classic infantile Pearson phenotype.
- name: Pancytopenia
category: Hematologic
description: Variable multilineage cytopenias accompany the sideroblastic anemia.
phenotype_term:
preferred_term: Pancytopenia
term:
id: HP:0001876
label: Pancytopenia
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: PS is characterized by pancytopenia (typically
explanation: GeneReviews names pancytopenia as a Pearson syndrome feature.
- name: Exocrine pancreatic insufficiency
category: Gastrointestinal
description: Exocrine pancreatic dysfunction contributes to malabsorption and poor growth.
phenotype_term:
preferred_term: Exocrine pancreatic insufficiency
term:
id: HP:0001738
label: Exocrine pancreatic insufficiency
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: exocrine pancreatic dysfunction, poor weight gain, and lactic acidosis.
explanation: GeneReviews supports exocrine pancreatic dysfunction in Pearson syndrome.
- name: Failure to thrive
category: Constitutional
description: Poor weight gain and failure to thrive are common multisystem manifestations.
phenotype_term:
preferred_term: Failure to thrive
term:
id: HP:0001508
label: Failure to thrive
evidence:
- reference: PMID:36253820
reference_title: "Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure."
supports: SUPPORT
evidence_source: OTHER
snippet: failure to thrive, muscle hypotonia, exocrine pancreas insufficiency, renal tubulopathy
explanation: The recent review includes failure to thrive among multisystem complications.
- name: Renal tubular acidosis
category: Renal
description: Renal tubular disease can manifest as renal tubular acidosis.
phenotype_term:
preferred_term: Renal tubular acidosis
term:
id: HP:0001947
label: Renal tubular acidosis
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: PS manifestations also include renal tubular acidosis, short stature, and elevated
explanation: GeneReviews lists renal tubular acidosis among Pearson manifestations.
- name: Lactic acidosis
category: Metabolic
description: Impaired oxidative phosphorylation elevates lactate and can cause acute metabolic crises.
phenotype_term:
preferred_term: Lactic acidosis
term:
id: HP:0003128
label: Lactic acidosis
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: exocrine pancreatic dysfunction, poor weight gain, and lactic acidosis.
explanation: GeneReviews lists lactic acidosis as a Pearson feature.
biochemical:
- name: Elevated lactate
presence: INCREASED
biomarker_term:
preferred_term: (S)-lactate
term:
id: CHEBI:16651
label: (S)-lactate
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: exocrine pancreatic dysfunction, poor weight gain, and lactic acidosis.
explanation: Lactic acidosis is the clinical biochemical readout of elevated lactate.
diagnosis:
- name: Mitochondrial DNA deletion testing
diagnosis_term:
preferred_term: genetic testing
term:
id: MAXO:0000127
label: genetic testing
description: >-
Molecular diagnosis is established by detecting a single large-scale mtDNA
deletion, often in blood, urine, buccal cells, or marrow in affected
children.
results: Detection of a single large-scale mtDNA deletion supports Pearson syndrome in the appropriate infantile clinical context.
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: (mtDNA) deletion ranging in size from 1.1 to 10 kb on molecular genetic testing.
explanation: GeneReviews defines molecular testing for single large-scale mtDNA deletion syndromes.
treatments:
- name: Transfusion and multidisciplinary supportive care
description: >-
Management is supportive and includes transfusion therapy for sideroblastic
anemia, pancreatic enzyme replacement when exocrine pancreatic insufficiency
is present, renal/electrolyte support, surveillance for cardiac and
endocrine complications, and coordinated mitochondrial-disease care.
treatment_term:
preferred_term: Supportive Care
term:
id: NCIT:C15747
label: Supportive Care
evidence:
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: transfusion therapy for individuals with PS with sideroblastic anemia;
explanation: GeneReviews supports transfusion therapy for Pearson sideroblastic anemia.
- reference: PMID:20301382
reference_title: Single Large-Scale Mitochondrial DNA Deletion Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: replacement of pancreatic enzymes for exocrine pancreatic insufficiency;
explanation: GeneReviews supports pancreatic enzyme replacement when exocrine pancreatic insufficiency is present.
notes: >-
Scope decision: Pearson syndrome is kept as a separate Disease entry because
it has a distinct MONDO identity (MONDO:0010797; OMIM:557000; ORPHA:699) and a
characteristic infantile marrow-pancreas presentation, even though it belongs
to the same SLSMD continuum as Kearns-Sayre syndrome. The shared mechanism is
captured in the Single Large-Scale mtDNA Deletion Disorders grouping.