Hereditary methemoglobinemia, recessive

Hereditary Methemoglobinemia, Recessive

Hereditary methemoglobinemia is a rare genetic disorder characterized by an abnormal amount of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that contains iron in the ferric state, which is unable to bind oxygen effectively. This condition leads to a reduced ability of the blood to release oxygen to tissues, resulting in a form of hypoxia.

1. 1. Pathophysiology

In hereditary methemoglobinemia, the enzyme cytochrome b5 reductase (also known as NADH methemoglobin reductase) is deficient or dysfunctional. This enzyme is responsible for reducing methemoglobin back to hemoglobin. When this enzyme is deficient, methemoglobin accumulates, leading to cyanosis and other symptoms of oxygen deprivation.

The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disease. Carriers, with only one copy of the mutated gene, typically do not show symptoms.

1. 1. Clinical Presentation

Patients with hereditary methemoglobinemia often present with cyanosis, which is a bluish discoloration of the skin and mucous membranes. This is due to the increased levels of methemoglobin, which gives the blood a chocolate-brown color. Other symptoms may include fatigue, shortness of breath, and in severe cases, neurological deficits due to hypoxia.

1. 1. Diagnosis

Diagnosis of hereditary methemoglobinemia is based on clinical presentation, family history, and laboratory tests. Blood tests reveal elevated levels of methemoglobin. Genetic testing can confirm mutations in the CYB5R3 gene, which encodes the cytochrome b5 reductase enzyme.

1. 1. Treatment

Treatment of hereditary methemoglobinemia involves the administration of methylene blue, which acts as an artificial electron donor to reduce methemoglobin back to hemoglobin. Ascorbic acid (vitamin C) can also be used as a reducing agent. In cases where methylene blue is ineffective or contraindicated, alternative treatments may be considered.

1. 1. Prognosis

The prognosis for individuals with hereditary methemoglobinemia is generally good with appropriate treatment. However, lifelong management may be necessary to prevent complications.

Also see

• Methemoglobinemia
• Cytochrome b5 reductase deficiency
• Autosomal recessive disorder
• Cyanosis