D-bifunctional protein deficiency

A rare genetic disorder affecting peroxisomal function

D-bifunctional protein deficiency is a rare genetic disorder that affects the normal functioning of peroxisomes, which are essential cellular organelles involved in various metabolic pathways, including the breakdown of very long-chain fatty acids (VLCFAs) and the synthesis of plasmalogens. This condition is characterized by a deficiency in the D-bifunctional protein, which is crucial for the peroxisomal beta-oxidation of VLCFAs.

Pathophysiology

D-bifunctional protein deficiency is caused by mutations in the HSD17B4 gene, which encodes the D-bifunctional protein. This protein has two enzymatic activities: enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase, both of which are necessary for the beta-oxidation of VLCFAs within peroxisomes. The deficiency leads to the accumulation of VLCFAs and other toxic metabolites, resulting in cellular damage and the clinical manifestations of the disease.

Clinical Features

The clinical presentation of D-bifunctional protein deficiency is variable but often includes severe neurological symptoms, such as hypotonia, seizures, and developmental delay. Other features may include hearing loss, vision problems, and liver dysfunction. The severity of symptoms can range from mild to severe, with some patients experiencing life-threatening complications in infancy.

Diagnosis

Diagnosis of D-bifunctional protein deficiency typically involves a combination of clinical evaluation, biochemical testing, and genetic analysis. Biochemical tests may reveal elevated levels of VLCFAs in the blood, while genetic testing can identify mutations in the HSD17B4 gene. Additional tests, such as magnetic resonance imaging (MRI) of the brain, may be used to assess neurological involvement.

Management

There is currently no cure for D-bifunctional protein deficiency, and treatment is primarily supportive and symptomatic. Management strategies may include dietary modifications to reduce VLCFA intake, physical therapy to address motor deficits, and medications to control seizures. Early intervention and a multidisciplinary approach are essential to optimize patient outcomes.

Prognosis

The prognosis for individuals with D-bifunctional protein deficiency varies depending on the severity of the condition. Severe forms of the disorder are often associated with significant neurological impairment and reduced life expectancy. However, milder forms may allow for a longer lifespan with appropriate management.

Related pages

• Peroxisomal disorders
• Very long-chain fatty acids
• HSD17B4 gene
• Neurological disorders