RARE DISEASE
Pearson syndrome
Pearson syndrome
Pearson syndrome
Synonyms: PMPS, Pearson marrow-pancreas syndrome
Synonyms: PMPS, Pearson marrow-pancreas syndrome
Synonyms: PMPS, Pearson marrow-pancreas syndrome
Drug discovery
1
drug
With orphan designation
Overview
Pearson syndrome is a rare, multisystem mitochondrial disorder caused by single large-scale mitochondrial DNA deletions, leading to bone marrow failure (sideroblastic anemia), pancreatic exocrine insufficiency, and metabolic crises. It typically manifests in infancy with lactic acidosis, failure to thrive, and multi-organ dysfunction. Approximately 50% of affected children die in early childhood; survivors often develop Kearns-Sayre syndrome [1][6][17].
Categories: rare endocrine diseases, rare gastroenterological diseases, rare genetic diseases, rare hematological diseases, rare inborn errors of metabolism
Research Papers
29 drug discovery papers about Pearson syndrome, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
29 drug discovery papers about Pearson syndrome, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-05-20 | Progressive short stature in Pearson syndrome and the impact of organ failure.
Pearson syndrome (PS) is a rare, unique primary mitochondrial disorder characterized by single large-scale mitochondrial DNA deletions, bone marrow failure, lactic acidosis, and progressive multi-organ complications. We retrospectively evaluated anthropometric data from 25 patients with PS. The median height, weight, and body mass index (BMI) standard deviation scores (SDS) at the last measurement were - 1.95 (range: -7.32 to 1.09), -1.70 (range: -12.26 to 0.11), and - 1.52 (range: -5.01 to 2.19), respectively; 50%, 40%, and 37.5% of patients, respectively, had values below -2 SDS. Longitudinal data from 18 patients showed that height and weight SDS declined progressively with age in most patients, whereas BMI SDS fluctuated without a clear age-related trend. Initiation of tube feeding improved weight and BMI SDS in some patients, while height SDS continued to decline without catch-up growth. Patients with organ failure exhibited an earlier decline in height SDS than those without organ failure. Patients with PS are generally short and underweight, and their short stature worsens over time. The presence of organ failure further exacerbates growth impairment.
2026-01-30 | Outcomes of kidney transplantation in three patients with single large-scale mitochondrial DNA deletion syndromes.
Single large-scale mitochondrial DNA deletion syndromes (SLSMDS) are a clinical continuum of three classic discrete clinical syndromes: Pearson marrow-pancreas syndrome, Kearns-Sayre syndrome, and chronic progressive ophthalmoplegia. Kidney manifestations, including chronic kidney disease with progression kidney failure has emerged as significant cause of morbidity and mortality in SLSMDS. Despite this recognition, reports of kidney transplantation in this population are limited. Here, we describe outcomes of kidney transplantation in three patients with SLSMDS and kidney failure over a 1-2.5-year follow-up period. All three patients had multisystem involvement at the time of transplantation. In all three patients, surgery was uncomplicated without evidence of acute metabolic decompensation in the perioperative period and standard immunosuppressive protocols were well tolerated. One patient developed post-transplant lymphoproliferative disease at 9 months status-post transplant which was ultimately fatal. The two surviving patients remain with stable graft function and functional quality of life at 1- and 3.5-years post-transplant.
2025-10-11 | Genotype-Phenotype Correlations in Chinese Pediatric Patients With Single Large-Scale Mitochondrial DNA Deletion Disorders.
This study investigated clinical and genetic characteristics of Chinese pediatric patients with single large-scale mitochondrial DNA deletions (SLSMD). We analyzed 28 patients (July 2004-March 2025) using long-range PCR and next-generation sequencing. Spearman correlation and ANOVA assessed genotype-phenotype relationships. Patients (mean age 5.52 ± 3.96 years) exhibited multi-organ involvement (5.43 ± 1.87 organs). Common initial presentations included ocular (29%), neurologic, and endocrine dysfunction. Only 14.3% had the classic 4977 bp deletion, and 23 novel deletions were identified in 25 patients. Larger deletions correlated with more deleted MRC complexes (r = 0.516, p = 0.0123) and more deleted tRNAs (r = 0.534, p = 0.0103). Kearns-Sayre syndrome (KSS) patients had later onset (p = 0.0337), larger deletions (p = 0.0263), and greater tRNA/MRC complex (p = 0.0263, p = 0.0319) involvement than non-KSS patients. SLSMD in Chinese children primarily causes KSS, Pearson syndrome (PS), and progressive ophthalmoplegia with multi-organ involvement. Genotype-phenotype correlations exist, particularly between deletion size, onset age, and disease severity. KSS patients show distinct genetic and clinical profiles, suggesting slower progression. This study expands the known SLSMD spectrum and underscores mitochondrial testing in pediatric multi-organ disorders.
2025-09-17 | Molecular Aspects of Mitochondrial Dysfunction in Diabetes, Pearson and Kearns-Sayre Syndromes, and Neurodegenerative Disorders.
Mitochondrial dysfunction results in complex pathophysiological alterations associated with clinical disease states including cancer, cardiovascular diseases, diabetes mellitus, and anxiety disorders. As a key organelle within mammalian cells, the mitochondrion serves as the energetic source of cellular function which are crucial to cellular homeostasis, and cell death. In this report, we review key molecular causes of mitochondrial dysfunction and discuss how it influences insulin resistance, Pearson Syndrome and Kearns-Sayre syndrome, the latter of which occur due to pathogenic variants in mitochondrial DNA that lead to direct cellular pathology. We discuss the molecular and cellular pathophysiological mechanisms, disease interplays, and clinical considerations related to these diseases influenced by mitochondrial dysfunction.
2025-07-22 | Mitophagy modulation rescues single large-scale mitochondrial DNA deletion (SLSMD) disease symptoms in the C. elegans uaDf5 animal model.
S ingle large s cale m itochondrial DNA (mtDNA) d eletions (SLSMD) underlie a range of sporadic or maternally inherited primary mitochondrial diseases having significant morbidity and mortality, including Pearson syndrome, Kearns-Sayre Syndrome, or Chronic Progressive External Ophthalmoplegia. Therapeutic development has been hindered by limited existing knowledge on mtDNA quality control and a lack of SLSMD animal models. To address this challenge, we utilized the C. elegans heteroplasmic SLSMD strain, uaDf5, to objectively screen for potential therapies. As mitophagy modulation has been implicated in mtDNA homeostasis, we screened a library of mitophagy modulating compounds to determine their comparative effects to rescue mitochondrial unfolded protein (UPR mt ) stress induction in in uaDf5 SLSMD worms. Interestingly, Thiamine was discovered to be an effective positive control, significantly reducing mitochondrial stress in this model. Two lead therapeutic candidates from the mitophagy library screen were Hemin and Celastrol (Tripterin). Celastrol is a mitophagy activating anti-inflammatory and metabolic modifying natural product derived compound, that rescued multiple fitness outcomes (thrashing, development, survival) and reduced the mitochondrial stress in uaDf5 animals in a mitophagy-dependent fashion. This study highlights the utility of the uaDf5 worm model to enable preclinical identification of therapeutic candidate leads for SLSMD-based heteroplasmic mtDNA diseases and identifies possible therapeutic candidates that serve as mitophagy modulators to improve health and specifically reduce heteroplasmy levels in SLSMD diseases.
2026-05-20 | Progressive short stature in Pearson syndrome and the impact of organ failure.
Pearson syndrome (PS) is a rare, unique primary mitochondrial disorder characterized by single large-scale mitochondrial DNA deletions, bone marrow failure, lactic acidosis, and progressive multi-organ complications. We retrospectively evaluated anthropometric data from 25 patients with PS. The median height, weight, and body mass index (BMI) standard deviation scores (SDS) at the last measurement were - 1.95 (range: -7.32 to 1.09), -1.70 (range: -12.26 to 0.11), and - 1.52 (range: -5.01 to 2.19), respectively; 50%, 40%, and 37.5% of patients, respectively, had values below -2 SDS. Longitudinal data from 18 patients showed that height and weight SDS declined progressively with age in most patients, whereas BMI SDS fluctuated without a clear age-related trend. Initiation of tube feeding improved weight and BMI SDS in some patients, while height SDS continued to decline without catch-up growth. Patients with organ failure exhibited an earlier decline in height SDS than those without organ failure. Patients with PS are generally short and underweight, and their short stature worsens over time. The presence of organ failure further exacerbates growth impairment.
2026-01-30 | Outcomes of kidney transplantation in three patients with single large-scale mitochondrial DNA deletion syndromes.
Single large-scale mitochondrial DNA deletion syndromes (SLSMDS) are a clinical continuum of three classic discrete clinical syndromes: Pearson marrow-pancreas syndrome, Kearns-Sayre syndrome, and chronic progressive ophthalmoplegia. Kidney manifestations, including chronic kidney disease with progression kidney failure has emerged as significant cause of morbidity and mortality in SLSMDS. Despite this recognition, reports of kidney transplantation in this population are limited. Here, we describe outcomes of kidney transplantation in three patients with SLSMDS and kidney failure over a 1-2.5-year follow-up period. All three patients had multisystem involvement at the time of transplantation. In all three patients, surgery was uncomplicated without evidence of acute metabolic decompensation in the perioperative period and standard immunosuppressive protocols were well tolerated. One patient developed post-transplant lymphoproliferative disease at 9 months status-post transplant which was ultimately fatal. The two surviving patients remain with stable graft function and functional quality of life at 1- and 3.5-years post-transplant.
2025-10-11 | Genotype-Phenotype Correlations in Chinese Pediatric Patients With Single Large-Scale Mitochondrial DNA Deletion Disorders.
This study investigated clinical and genetic characteristics of Chinese pediatric patients with single large-scale mitochondrial DNA deletions (SLSMD). We analyzed 28 patients (July 2004-March 2025) using long-range PCR and next-generation sequencing. Spearman correlation and ANOVA assessed genotype-phenotype relationships. Patients (mean age 5.52 ± 3.96 years) exhibited multi-organ involvement (5.43 ± 1.87 organs). Common initial presentations included ocular (29%), neurologic, and endocrine dysfunction. Only 14.3% had the classic 4977 bp deletion, and 23 novel deletions were identified in 25 patients. Larger deletions correlated with more deleted MRC complexes (r = 0.516, p = 0.0123) and more deleted tRNAs (r = 0.534, p = 0.0103). Kearns-Sayre syndrome (KSS) patients had later onset (p = 0.0337), larger deletions (p = 0.0263), and greater tRNA/MRC complex (p = 0.0263, p = 0.0319) involvement than non-KSS patients. SLSMD in Chinese children primarily causes KSS, Pearson syndrome (PS), and progressive ophthalmoplegia with multi-organ involvement. Genotype-phenotype correlations exist, particularly between deletion size, onset age, and disease severity. KSS patients show distinct genetic and clinical profiles, suggesting slower progression. This study expands the known SLSMD spectrum and underscores mitochondrial testing in pediatric multi-organ disorders.
2025-09-17 | Molecular Aspects of Mitochondrial Dysfunction in Diabetes, Pearson and Kearns-Sayre Syndromes, and Neurodegenerative Disorders.
Mitochondrial dysfunction results in complex pathophysiological alterations associated with clinical disease states including cancer, cardiovascular diseases, diabetes mellitus, and anxiety disorders. As a key organelle within mammalian cells, the mitochondrion serves as the energetic source of cellular function which are crucial to cellular homeostasis, and cell death. In this report, we review key molecular causes of mitochondrial dysfunction and discuss how it influences insulin resistance, Pearson Syndrome and Kearns-Sayre syndrome, the latter of which occur due to pathogenic variants in mitochondrial DNA that lead to direct cellular pathology. We discuss the molecular and cellular pathophysiological mechanisms, disease interplays, and clinical considerations related to these diseases influenced by mitochondrial dysfunction.
2025-07-22 | Mitophagy modulation rescues single large-scale mitochondrial DNA deletion (SLSMD) disease symptoms in the C. elegans uaDf5 animal model.
S ingle large s cale m itochondrial DNA (mtDNA) d eletions (SLSMD) underlie a range of sporadic or maternally inherited primary mitochondrial diseases having significant morbidity and mortality, including Pearson syndrome, Kearns-Sayre Syndrome, or Chronic Progressive External Ophthalmoplegia. Therapeutic development has been hindered by limited existing knowledge on mtDNA quality control and a lack of SLSMD animal models. To address this challenge, we utilized the C. elegans heteroplasmic SLSMD strain, uaDf5, to objectively screen for potential therapies. As mitophagy modulation has been implicated in mtDNA homeostasis, we screened a library of mitophagy modulating compounds to determine their comparative effects to rescue mitochondrial unfolded protein (UPR mt ) stress induction in in uaDf5 SLSMD worms. Interestingly, Thiamine was discovered to be an effective positive control, significantly reducing mitochondrial stress in this model. Two lead therapeutic candidates from the mitophagy library screen were Hemin and Celastrol (Tripterin). Celastrol is a mitophagy activating anti-inflammatory and metabolic modifying natural product derived compound, that rescued multiple fitness outcomes (thrashing, development, survival) and reduced the mitochondrial stress in uaDf5 animals in a mitophagy-dependent fashion. This study highlights the utility of the uaDf5 worm model to enable preclinical identification of therapeutic candidate leads for SLSMD-based heteroplasmic mtDNA diseases and identifies possible therapeutic candidates that serve as mitophagy modulators to improve health and specifically reduce heteroplasmy levels in SLSMD diseases.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Pearson syndrome.
1 orphan drug designation for Pearson syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
autologous CD34+ Cells Enriched with Blood Derived Mitochondria | cell therapies | FDA | 2019-02-26 | — | Minovia Therapeutics Ltd. |
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