Broadening the phenotypic spectrum of Pearson syndrome: Five new cases and a review of the literature

Wild, K. Taylor; Goldstein, Amy; Muraresku, Colleen; Ganetzky, Rebecca

doi:10.1002/ajmg.a.61433

Cited by 30 publications

(34 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pearson syndrome is a multisystem disorder due to the mitochondrial respiratory chain deficit characterized by exocrine pancreatic insufficiency and sideroblastic anemia from the first year of life, with a poor prognosis. The rare children who survive may progress to KSS later in life [ 49 ].…”

Section: Clinical Picturesmentioning

confidence: 99%

Mitochondrial Syndromes Revisited

Orsucci¹,

Ienco²,

Rossi³

et al. 2021

JCM

View full text Add to dashboard Cite

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype–phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

show abstract

Section: Clinical Picturesmentioning

confidence: 99%

Mitochondrial Syndromes Revisited

Orsucci¹,

Ienco²,

Rossi³

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…If the single deletion appears and expands in a late stage of foetal development, the clinical phenotype may be limited mostly to the muscle tissue and express as a CPEO spectrum disorder [9,101]. If the mutational event occurs at earlier stages, this may involve a larger range of tissues expressing as KSS [38,39], with the extreme phenotype of PS [40,41], characterized by pancytopenia, which may resolve and evolve later in life into KSS [102]. Confirming this view, cases with early‐onset and wider constellation of multi‐organ symptoms and signs have been reported associated with large proportions of single mtDNA deletion in liver, kidney, skeletal muscle and blood cells [103].…”

Section: Mitochondrial Diseases With Primary Mutations Affecting Mtdnamentioning

confidence: 99%

Mitochondrial diseases in adults

et al. 2020

View full text Add to dashboard Cite

Mitochondrial medicine is a field that expanded exponentially in the last 30 years. Individually rare, mitochondrial diseases as a whole are probably the most frequent genetic disorder in adults. The complexity of their genotype–phenotype correlation, in terms of penetrance and clinical expressivity, natural history and diagnostic algorithm derives from the dual genetic determination. In fact, in addition to the about 1.500 genes encoding mitochondrial proteins that reside in the nuclear genome (nDNA), we have the 13 proteins encoded by the mitochondrial genome (mtDNA), for which 22 specific tRNAs and 2 rRNAs are also needed. Thus, besides Mendelian genetics, we need to consider all peculiarities of how mtDNA is inherited, maintained and expressed to fully understand the pathogenic mechanisms of these disorders. Yet, from the initial restriction to the narrow field of oxidative phosphorylation dysfunction, the landscape of mitochondrial functions impinging on cellular homeostasis, driving life and death, is impressively enlarged. Finally, from the clinical standpoint, starting from the neuromuscular field, where brain and skeletal muscle were the primary targets of mitochondrial dysfunction as energy‐dependent tissues, after three decades virtually any subspecialty of medicine is now involved. We will summarize the key clinical pictures and pathogenic mechanisms of mitochondrial diseases in adults.

show abstract

“…Pearson syndrome (PS) is a rare constitutional disorder usually caused by single, large-scale mitochondrial DNA deletions that result in bone marrow failure and severe macrocytic sideroblastic anemia. [1][2][3][4][5] It affects multiple organ systems, and is frequently associated with pancreatic insufficiency resulting in steatorrhea and malabsorption. [5] Prognosis is poor (~20% 5-year survival) due to the multifaceted nature of the disease, which includes defective cellular metabolism, malabsorption, renal and hepatic failure, and endocrine dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5] It affects multiple organ systems, and is frequently associated with pancreatic insufficiency resulting in steatorrhea and malabsorption. [5] Prognosis is poor (~20% 5-year survival) due to the multifaceted nature of the disease, which includes defective cellular metabolism, malabsorption, renal and hepatic failure, and endocrine dysfunction. We are reporting a 9-month-old male who presented with severe macrocytic anemia and severe pancreatic insufficiency requiring multiple blood transfusions and pancreatic enzyme replacement.…”

Section: Introductionmentioning

confidence: 99%

Advances in Diagnosis of Mitochondrial Diseases: Case Report of an Infant with Pearson Syndrome

2021

IJCR

View full text Add to dashboard Cite

Pearson syndrome (PS) is a mitochondrial disorder that presents in early infancy as a multisystemic disease affecting the bone marrow and pancreas. It may present with anemia, diarrhea, exocrine pancreatic dysfunction, and failure to thrive.[1] Delay in diagnosis can lead to severe morbidity and mortality in infancy. We report the case of a 9-month-old presenting with failure to thrive, severe macrocytic anemia and pancytopenia initially thought to have gastroesophageal reflux and feeding intolerance. Severe macrocytic anemia and pancytopenia prompted an early bone marrow evaluation. Abnormal bone marrow findings including vacuolated marrow precursors and ringed sideroblasts along with persistent mild lactic acidosis led to a rapid and extensive genetics workup. Whole exome sequencing including mitochondrial genome sequencing detected a 2.3 kb heteroplasmic deletion in m.12113_14421 encompassing the MT-ND5 gene consistent with the diagnosis of Pearson Syndrome. This case report highlights the advances in molecular genetic testing to diagnose patients with complex medical histories along the spectrum of mitochondrial diseases and the importance of early diagnosis to start treatment.

show abstract

Broadening the phenotypic spectrum of Pearson syndrome: Five new cases and a review of the literature

Cited by 30 publications

References 18 publications

Mitochondrial Syndromes Revisited

Mitochondrial Syndromes Revisited

Mitochondrial diseases in adults

Advances in Diagnosis of Mitochondrial Diseases: Case Report of an Infant with Pearson Syndrome

Contact Info

Product

Resources

About