-
American Journal of Ophthalmology Case... Jun 2024To describe a case with Leber's hereditary optic neuropathy (LHON) like optic atrophy in the presence of gene variant m.8969G > A.
PURPOSE
To describe a case with Leber's hereditary optic neuropathy (LHON) like optic atrophy in the presence of gene variant m.8969G > A.
OBSERVATIONS
A 20-year-old patient with a history of mild developmental delay, mild cognitive impairment, and positional tremor presented with subacute painless visual loss over a few weeks. Mitochondrial genome sequencing revealed a variant in , m.8969G > A (p.Ser148Asn). This variant was previously reported in association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) and with nephropathy, followed by brain atrophy, muscle weakness and arrhythmias, but not with optic atrophy.
CONCLUSIONS AND IMPORTANCE
Rare variants in can also cause LHON like optic atrophy. It is important to perform further genetic analysis of mitochondrial DNA in genetically unsolved cases suspected of Leber's hereditary optic neuropathy to confirm the clinical diagnosis.
PubMed: 38756953
DOI: 10.1016/j.ajoc.2024.102070 -
Current Oncology (Toronto, Ont.) Mar 2024Myelodysplastic neoplasms (MDS) with ring sideroblasts (RS) are diagnosed via bone marrow aspiration in the presence of either (i) ≥15% RS or (ii) 5-14% RS and an...
Myelodysplastic Neoplasms (MDS) with Ring Sideroblasts or Mutations: The Improved Clinical Utility of World Health Organization and International Consensus Classification 2022 Definitions, a Single-Centre Retrospective Chart Review.
Myelodysplastic neoplasms (MDS) with ring sideroblasts (RS) are diagnosed via bone marrow aspiration in the presence of either (i) ≥15% RS or (ii) 5-14% RS and an mutation. In the MEDALIST trial and in an interim analysis of the COMMANDS trial, lower-risk MDS-RS patients had decreased transfusion dependency with luspatercept treatment. A total of 6817 patients with suspected hematologic malignancies underwent molecular testing using a next-generation-sequencing-based genetic assay and 395 MDS patients, seen at our centre from 1 January 2018 to 31 May 2023, were reviewed. Of these, we identified 39 evaluable patients as having lower-risk MDS with mutations: there were 20 (51.3%) males and 19 (48.7%) females, with a median age of 77 years (range of 57 to 92). Nineteen (48.7%) patients had an isolated mutation with a mean variant allele frequency of 35.2% +/- 8.1%, ranging from 7.4% to 46.0%. There were 29 (74.4%) patients with ≥15% RS, 6 (15.4%) with 5 to 14% RS, one (2.6%) with 1% RS, and 3 (7.7%) with no RS. Our study suggests that a quarter of patients would be missed based on the morphologic criterion of only using RS greater than 15% and supports the revised 2022 definitions of the World Health Organization (WHO) and International Consensus Classification (ICC), which shift toward molecularly defined subtypes of MDS and appropriate testing.
Topics: Humans; RNA Splicing Factors; Male; Female; Aged; Mutation; Myelodysplastic Syndromes; World Health Organization; Middle Aged; Retrospective Studies; Aged, 80 and over; Phosphoproteins; Anemia, Sideroblastic
PubMed: 38668037
DOI: 10.3390/curroncol31040134 -
IScience Mar 2024Pseudouridylation plays a regulatory role in various physiological and pathological processes. A prime example is the mitochondrial myopathy, lactic acidosis, and...
Pseudouridylation plays a regulatory role in various physiological and pathological processes. A prime example is the mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome (MLASA), characterized by defective pseudouridylation resulting from genetic mutations in pseudouridine synthase 1 (PUS1). However, the roles and mechanisms of pseudouridylation in normal erythropoiesis and MLASA-related anemia remain elusive. We established a mouse model carrying a point mutation (R110W) in the enzymatic domain of PUS1, mimicking the common mutation in human MLASA. -mutant mice exhibited anemia at 4 weeks old. Impaired mitochondrial oxidative phosphorylation was also observed in mutant erythroblasts. Mechanistically, mutant erythroblasts showed defective pseudouridylation of targeted tRNAs, altered tRNA profiles, decreased translation efficiency of ribosomal protein genes, and reduced globin synthesis, culminating in ineffective erythropoiesis. Our study thus provided direct evidence that pseudouridylation participates in erythropoiesis We demonstrated the critical role of pseudouridylation in regulating tRNA homeostasis, cytoplasmic translation, and erythropoiesis.
PubMed: 38450158
DOI: 10.1016/j.isci.2024.109265 -
Clinical Case Reports Dec 2023Dolutegravir, the most recent antiretroviral drug with high efficacy, good tolerability, infrequent drug-drug interactions, and a favorable safety profile has not been...
Dolutegravir, the most recent antiretroviral drug with high efficacy, good tolerability, infrequent drug-drug interactions, and a favorable safety profile has not been reported in current literature as a cause of acquired sideroblastic anemia. Here, we present a 35-year-old male patient who was diagnosed with acquired sideroblastic anemia to Dolutegravir therapy.
PubMed: 38084360
DOI: 10.1002/ccr3.8301 -
Mediterranean Journal of Hematology and... 2023
PubMed: 38028395
DOI: 10.4084/MJHID.2023.062 -
Diagnostics (Basel, Switzerland) Jul 2023Treatment of Wilson's disease (WD), an inherited disease characterized by copper overload, is lifelong and there is the possibility that copper deficiency (CD) may... (Review)
Review
BACKGROUND
Treatment of Wilson's disease (WD), an inherited disease characterized by copper overload, is lifelong and there is the possibility that copper deficiency (CD) may occur. We systematically reviewed the literature to describe treatment patterns, symptoms and outcomes associated with CD.
METHODS
Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, the PubMed database was searched up to 6 April 2023.
RESULTS
Across 17 articles, 20 cases of CD were described, most commonly (15 cases) in WD patients treated with zinc salts (ZS), less often on combined chelator and ZS therapy (3 cases), molybdate salts plus ZS (1), or molybdate alone (1). CD symptoms occurred insidiously, including sideroblastic anemia, neutropenia, axonal sensory neuropathy, posterior cord myelopathy and increased ratio of epileptic seizures (or epilepsy). CD diagnosis was based on symptoms and severely reduced urinary copper excretion (<20 µg/24 h [<0.3 µmol/24 h] on ZS, or <100 µg/24 h [<1.6 µmol/24 h] on chelators) with low total serum copper and ceruloplasmin.
CONCLUSIONS
Awareness of CD and regular monitoring of copper metabolism is needed during WD treatment. Temporary cessation of anti-copper treatment usually reverses serum copper reductions as well as pancytopenia; however, some symptoms, especially neuropathy and myelopathy, may persist.
PubMed: 37510170
DOI: 10.3390/diagnostics13142424