Hemoglobin Disorders Associated with Neurological Impairment: First Report of ATR-X Syndrome and Recessive Congenital Methemoglobinemia Type II in Tunisia.

Hemoglobin disorders are among the most common inherited diseases worldwide. Their clinical manifestations range from anemia to more severe forms associated with neurological impairments. These complications can result as secondary consequences of the disease's clinical manifestations or be directly linked to genetic mutations. In this study, we present two families with neurological impairments who were referred to us for complementary hematological and biochemical analyses. Complete blood count, methemoglobin level, and methemoglobin reductase activity were assessed. Molecular analyses were performed using whole-exome sequencing, and the segregation of the identified mutations was confirmed with direct sequencing. Their pathogenicity and conservation were evaluated using various bioinformatics tools. Clinical and hematological findings suggested X-linked alpha-thalassemia/impaired intellectual development syndrome in the first family and recessive congenital methemoglobinemia type II in the second. This was confirmed by the identification of pathogenic mutations