遺伝性鉄芽球性貧血

TRNT1 deficiency (SIFD syndrome) is a rare inborn error of immunity characterized by sideroblastic anemia, immunodeficiency, periodic fevers, and developmental delay. We report two Romanian patients with genetically confirmed TRNT1 deficiency presenting with characteristic hematologic and immunologic abnormalities and a distinctive facial dysmorphism. One patient additionally developed severe gastrointestinal ischemia and intracranial hemorrhage in the setting of concomitant hereditary antithrombin III deficiency. These observations expand the phenotypic spectrum associated with TRNT1 deficiency and highlight the marked clinical variability of this disorder. The contribution of TRNT1-associated inflammation to the vascular phenotype remains speculative and cannot be distinguished from the effects of the concomitant thrombophilic condition.

BACKGROUND: Congenital sideroblastic anemia (CSA) and thalassemia are both hereditary disorders of erythropoiesis, primarily affecting erythroid cells. Their typical manifestations include anemia and iron overload. In this study, we conducted clinical and molecular analyses on a male patient who was concurrently diagnosed with thalassemia and CSA. METHODS: The patient underwent a series of tests including complete blood count, bone marrow smear, and serum ferritin levels. Whole exome sequencing technology was employed for genetic mutation analysis, and bioinformatics methods were utilized to assess the functional impact of the predicted variants. RESULTS: The patient was previously diagnosed with alpha thalassemia (with genotype of --SEA/-α4.2), and has been receiving frequent blood transfusions over the past two years, presenting with severe anemia (Hb level of 44 g/L), iron overload, and 52% ring sideroblasts in the bone marrow. Whole exome sequencing revealed a hemizygous nonsense mutation (c.224 C > A) in the 5-aminolevulinate synthase (ALAS2) gene, which introduces a premature stop codon at the 75th amino acid position in the N-terminal region (P.S75X). Family analysis showed that the patient, her mother, and her sister all carry this variant, suggesting it is a de novo mutation. Computational analysis using various online software tools predicted the variant to be deleterious. The patient was treated with a combination of vitamin B₆, folic acid, and deferasirox. After six months, the Hb level increased to 104 g/L, while the serum ferritin level initially rose and subsequently decreased. CONCLUSION: This study identified and reported a novel variant, ALAS2 c.224 C > A (P.S75X), which led to the co-occurrence of sideroblastic anemia in a male patient with thalassemia. The anemia symptoms induced by this variant were responsive to pyridoxine (vitamin B₆) supplementation therapy.

X-linked sideroblastic anemia (XLSA) is categorized as hypochromic microcytic anemia. In 3 children with XLSA, we observed prominent elliptocytosis, and red cell band 3 content histograms were similar to those found in hereditary elliptocytosis, thus validating Cooley's descriptions in 1945.

Ferritin is the protein that serves as the main mechanism for iron storage. It can also be an acute-phase reactant, which may rise in response to inflammation, infection, injury, autoimmune disease, or malignancy. Therefore, when evaluating ferritin levels, it is important to consider both iron storage and potential underlying conditions that could cause hyperferritinemia. We report a case of an elderly man in his late 80s who had elevated ferritin levels for years before ultimately being diagnosed with metastatic neuroendocrine carcinoma. The initial diagnosis was suspected to be due to iron overload from iatrogenic causes, but despite discontinuation of iron supplementation, the patient continued to have hyperferritinemia. Broad differential diagnoses were considered, including hereditary hemochromatosis, sideroblastic anemia, thalassemia, viral infection, hereditary hyperferritinemia, myelodysplastic syndromes with ineffective iron regulation, hemophagocytic lymphohistiocytosis, and other autoimmune phenomena. However, workup was negative. Ultimately, bone marrow biopsy was performed, which revealed poorly differentiated metastatic carcinoma with neuroendocrine differentiation.

X-linked sideroblastic anaemia (XLSA) is a rare hereditary disorder caused by mutations in the ALAS2 gene, essential for haem biosynthesis. We report two male siblings, the first of whom developed severe microcytic hypochromic anaemia requiring regular transfusions, iron chelation and an allogeneic bone marrow transplant, while his brother displayed only mild microcytic hypochromic indices without anaemia. Initial genetic screening did not identify a pathogenic variant. However, duo exome sequencing later revealed an intronic ALAS2 mutation, initially categorised as of uncertain significance and subsequently reclassified as pathogenic. This case underscores the diagnostic challenges posed by intronic mutations and the highly variable expressivity of XLSA, even among siblings. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.