D-bifunctional protein deficiency is an inherited condition that presents a problem with the cell’s ability to metabolize the fatty acids. This can cause severe neurodegeneration that can begin in the early infancy. As the result of the associated symptoms, the infants usually don’t attain their developmental milestones such as the control of head movement and death occurs by the age of two. This deficiency is estimated to affect around 1 in 100,000 newborns.
Causes
This condition is inherited in an autosomal recessive pattern meaning one copy of the gene in each cell can cause this disorder. Each individual carry two copies of a gene. The carriers of this condition have a mutation in one copy of the gene, while individuals with the D-bifunctional protein deficiency present mutation in both the copies of their genes. The parents of the affected individual may each be the carrier of this condition and may not exhibit any signs and symptom associated with this disorder.
The D-bifunctional protein deficiency is caused by a mutation in the gene HSD17B4. The enzyme produced by this gene is known as the D-functional protein that is detected in the peroxisomes of the cellular structures and metabolizes the fatty acids. The genetic mutation can impair the function of the enzymatic activities causing problems with the effective breakdown of the fatty acids resulting in its accumulation in the body. Although this abnormality is associated with the features that are present in the D-bifunctional protein deficiency, the neurological and non-neurological cause resulting from the fatty acid accumulation remains unclear. However, the abnormal accumulation may cause problems with the normal development of the brain and the breakdown of myelin. The destruction of myelin can affect the transmission of nerve signals and the loss of myelin-containing tissue known as the white matter.
Symptoms
This occurs as the deterioration of the nervous system affecting early infancy. The symptoms consist of weak muscle tone (hypotonia) and seizures. These infants are unable to reach their developmental milestones and additionally present loss of vision and hearing. The additional abnormal facial features can include the high forehead, widely spaced eyes and high arch of the palate at the roof of the mouth. Other abnormalities can include the unusual space present between the bones of the skull (fontanel), mental retardation and enlarged liver (hepatomegaly).
Diagnosis
The D-bifunctional protein deficiency can be diagnosed based on the increased level of very long-chain fatty acids, the bile acid intermediates dihydroxycholestanoic acid (DHCA), pristanic acid, pytanic acid and trihydroxycholestanoic acid (THCA). In addition, the genetic molecular testing can identify the gene that is responsible for causing this condition.
Treatment
There is no cure for D-bifunctional protein deficiency and the treatment is usually a supportive care for the symptoms. This is a fatal condition and the affected infants do not survive past age two with survival rarely exceeding to late childhood. However, research is continued to determine if stem cell transplant can benefit these affected cases.
References
https://rarediseases.info.nih.gov/diseases/4539/dbifunctional-protein-deficiency
https://nxgenmdx.com/wp-content/uploads/2015/02/D-Bifunctional-Protein-Deficiency.pdf
https://ghr.nlm.nih.gov/condition/d-bifunctional-protein-deficiency#diagnosis
