From the Guidelines
Mitochondrial diseases that cause hematologic or bone marrow disturbances include sideroblastic anemia due to defects in SLC25A38, which is a protein on the inner membrane of the mitochondria of hematopoietic cells. This condition is characterized by severe congenital sideroblastic anemia with microcytic hypochromic erythrocytes, and its inheritance pattern is autosomal recessive 1. The clinical presentation of this disease includes severe, often transfusion-dependent microcytic hypochromic anemia in childhood, which is clinically similar to thalassemia major, with bone marrow smears showing ring sideroblasts and increased serum ferritin levels and TSAT 1. Key features of this condition include:
- Severe congenital sideroblastic anemia
- Microcytic hypochromic erythrocytes
- Autosomal recessive inheritance pattern
- Ring sideroblasts in bone marrow smears
- Increased serum ferritin levels and TSAT Treatment for this condition consists of symptomatic treatment with erythrocyte transfusions and iron chelation, and hematopoietic stem cell transplantation (HSCT) is the only curative treatment 1. It is essential to note that early diagnosis through genetic testing and multidisciplinary care are crucial for managing these complex disorders. The pathogenesis of this disease involves defects in the SLC25A38 protein, which is essential for heme synthesis, and its specific function is not known, but it has been hypothesized that SLC25A38 facilitates 5-ALA production by importing glycine into mitochondria or by exchanging glycine for ALA across the mitochondrial inner membrane 1.
From the Research
Mitochondrial Diseases Causing Hematologic or Bone Marrow Disturbances
- The following mitochondrial diseases can cause hematologic or bone marrow disturbances:
- Pearson syndrome: characterized by pancytopenia, anemia, and bone marrow failure 2, 3, 4
- Kearns-Sayre syndrome: associated with anemia 2, 3
- Barth syndrome: characterized by neutropenia 2
- Autosomal recessive mitochondrial myopathy, lactic acidosis and sideroblastic anemia syndrome: associated with sideroblastic anemia 2
- Leigh's syndrome: anemia has been described in single cases 2
- MERRF (myoclonic epilepsy and ragged-red fiber) syndrome: anemia has been described in single cases 2
- Leber's hereditary optic neuropathy: anemia has been described in single cases 2
- Friedreich's ataxia: anemia has been described in single cases 2
- These diseases can manifest with various hematological abnormalities, including:
- Aplastic anemia
- Megaloblastic anemia
- Sideroblastic anemia
- Leukopenia
- Neutropenia
- Thrombocytopenia
- Pancytopenia
- Eosinophilia 2
- Bone marrow features in Pearson syndrome include: