Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia

Gagne, Katelyn E.; Ghazvinian, Roxanne; Yuan, Daniel; Zon, Rebecca L.; Storm, Kelsie; Mazur-Popinska, Magdalena; Andolina, Laura; Bubała, H; Golebiowska, Sydonia; Higman, Meghan A.; Kałwak, Krzysztof; Kurre, Peter; Matysiak, Michał; Niewiadomska, Edyta; Pels, Salley; Petruzzi, Mary Jane; Pobudejska-Pieniążek, Aneta; Szczepański, Tomasz; Fleming, Mark D.; Gazda, Hanna T.; Agarwal, Suneet

doi:10.1182/blood-2014-01-545830

Cited by 47 publications

(39 citation statements)

References 21 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…53,54 Some patients present with hematological abnormalities alone, and may even exhibit "pure red cell aplasia," being mistaken for Diamond-Blackfan anemia. 55 Many often have other cytopenias. Approximately half of patients carry a 4977-bp mitochondrial DNA deletion that is common to other mitochondrial cytopathies (eg, Kearns-Sayre syndrome).…”

Section: Isc Biogenesis and Csamentioning

confidence: 99%

The molecular genetics of sideroblastic anemia

Ducamp

Fleming

2019

Blood

Self Cite

View full text Add to dashboard Cite

The sideroblastic anemias (SAs) are a group of inherited and acquired bone marrow disorders defined by pathological iron accumulation in the mitochondria of erythroid precursors. Like most hematological diseases, the molecular genetic basis of the SAs has ridden the wave of technology advancement. Within the last 30 years, with the advent of positional cloning, the human genome project, solid-state genotyping technologies, and next-generation sequencing have evolved to the point where more than two-thirds of congenital SA cases, and an even greater proportion of cases of acquired clonal disease, can be attributed to mutations in a specific gene or genes. This review focuses on an analysis of the genetics of these diseases and how understanding these defects may contribute to the design and implementation of rational therapies.

show abstract

Section: Isc Biogenesis and Csamentioning

confidence: 99%

The molecular genetics of sideroblastic anemia

Ducamp

Fleming

2019

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…Sometimes, the associated features may be subtle or not yet fully developed at the time of presentation (Bottomley & Fleming, ). Some patients with Pearson Marrow‐Pancreas Syndrome (PMPS, Online Mendelian Inheritance in Man [OMIM ® ] number 557000) with only haematological abnormalities have been reported (Gagne et al , ). So far, 3 non‐syndromic forms have been reported and linked to different mutations ( ALAS2, SLC25A38 and GLRX5 ): the X‐linked sideroblastic anaemia (XLSA, OMIM number 300751) caused by ALAS2 mutations, the severe microcytic anaemia linked to mutations in the mitochondrial transporter SLC25A38 recently described as the cause of an autosomal‐recessive non‐syndromic form of CSA (Guernsey et al , ) and the severe sideroblastic anaemia associated with a homozygous splice site mutation in GLRX5 (an integral component of the Fe‐S cluster assembly machinery within mitochondria) (Camaschella et al , ).…”

Section: Introductionmentioning

confidence: 99%

Genotype/phenotype correlations of childhood‐onset congenital sideroblastic anaemia in a European cohort

et al. 2019

View full text Add to dashboard Cite

Congenital sideroblastic anaemia (CSA) is a rare disease caused by germline mutations of genes involved in haem and iron-sulphur cluster formation, and mitochondrial protein biosynthesis. We performed a retrospective multicentre European study of a cohort of childhood-onset CSA patients to explore genotype/phenotype correlations. We studied 23 females and 20 males with symptoms of CSA. Among the patients, the most frequently mutated genes were ALAS2 (n = 10; 23Á3%) and SLC25A38 (n = 8; 18Á6%), causing isolated forms of microcytic anaemia of varying severity. Five patients with SLC19A2 mutations suffered from thiamine-responsive megaloblastic anaemia and three exhibited the 'anaemia, deafness and diabetes' triad. Three patients with TRNT1 mutations exhibited severe early onset microcytic anaemia associated with thrombocytosis, and two exhibited Bcell immunodeficiency, inflammatory syndrome and psychomotor delay. The prognoses of patients with TRNT1 and SLC2A38 mutations were generally dismal because of comorbidities or severe iron overload. No molecular diagnosis could be established in 14/43 cases. This study emphasizes the frequency of ALAS2 and SLC25A38 mutations and provides the largest comprehensive analysis to date of genotype/phenotype correlations in CSA. Further studies of CSA patients with data recorded in an international registry would be helpful to improve patient management and establish standardized guidelines.

show abstract

“…The authors propose that all patients with presumptive DBA should be tested for mitochondrial DNA (mtDNA) deletion during their initial genetic evaluation. 1 …”

mentioning

confidence: 99%