NADH cytochrome B5 reductase deficiency

NADH cytochrome b5 reductase deficiency is a rare genetic disorder characterized by a deficiency in the enzyme NADH cytochrome b5 reductase, which is crucial for the electron transport chain in mitochondria. This deficiency leads to a variety of clinical manifestations, primarily affecting the blood, nervous system, and skin. The disorder is also known as Methemoglobinemia, type II, when it manifests with high levels of methemoglobin in the blood, leading to cyanosis (blue discoloration of the skin and mucous membranes).

Causes

NADH cytochrome b5 reductase deficiency is caused by mutations in the CYB5R3 gene, which encodes the NADH cytochrome b5 reductase enzyme. These mutations lead to either a partial or complete lack of enzyme activity. The enzyme's role is to reduce methemoglobin back to hemoglobin, and its deficiency results in the accumulation of methemoglobin, which is unable to carry oxygen effectively.

Symptoms

The symptoms of NADH cytochrome b5 reductase deficiency can vary widely among affected individuals. The most common symptom is cyanosis, which is noticeable shortly after birth. Other symptoms may include:

• Fatigue and weakness due to anemia
• Developmental delays
• Intellectual disability
• Neurological issues, such as seizures
• Compromised immune system function

Diagnosis

Diagnosis of NADH cytochrome b5 reductase deficiency involves a combination of clinical evaluation and laboratory tests. Blood tests can reveal elevated levels of methemoglobin. Genetic testing can confirm mutations in the CYB5R3 gene, providing a definitive diagnosis.

Treatment

Treatment for NADH cytochrome b5 reductase deficiency focuses on managing symptoms and preventing complications. Methylene blue can be used to reduce methemoglobin levels in the blood, although its effectiveness may vary. Ascorbic acid (vitamin C) has also been used as a treatment to reduce methemoglobin levels. In severe cases, blood transfusions may be necessary. Ongoing monitoring and supportive care are important to manage the condition effectively.

Prognosis

The prognosis for individuals with NADH cytochrome b5 reductase deficiency varies depending on the severity of the enzyme deficiency and the effectiveness of treatment. Early diagnosis and treatment can improve the quality of life and reduce the risk of serious complications.