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HomeHealth articlesd-bifunctional protein deficiencyWhat Is D-Bifunctional Protein Deficiency?

D-Bifunctional Protein Deficiency - Symptoms, Causes, Diagnosis, and Treatment

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D-Bifunctional Protein Deficiency - Symptoms, Causes, Diagnosis, and Treatment

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D-bifunctional protein deficiency is a genetic disorder that affects the nervous system. To know more about D-bifunctional protein deficiency, read the article given below.

Medically reviewed by

Dr. Kaushal Bhavsar

Published At August 1, 2022
Reviewed AtMarch 7, 2023

What Is D-Bifunctional Protein Deficiency?

D-bifunctional protein is mainly found in peroxisomes. Peroxisomes are sac-like structures found in the cells of the human body. The peroxisomes are primarily involved in the oxidation of fatty acids and amino acids. The hydrogen peroxide formed from these reactions is converted to water and oxygen by the reactions that happen inside the peroxisomes. D-functional protein plays a vital role in breaking down fatty acids in peroxisomes. The D-bifunctional protein is also known as multifunctional protein-2 or multifunctional enzyme-2. The D-bifunctional protein has two parts with enzyme (proteins that speed up the reactions) activity - hydratase and dehydrogenase domains. These domains play an essential role in the fatty acid oxidation pathway. In this process, with the help of D-functional protein, two carbon atoms are removed from every fatty acid molecule and are converted to a molecule called acetyl-CoA, which is reused by the cell.

Due to the genetic disorder in some individuals, there is a deficiency of D-bifunctional protein. It can interfere with fatty acid metabolism. It can result in the buildup of fatty acids in the body. It is also accompanied by deterioration of nervous system functions. This condition is known as D-bifunctional protein deficiency (DBP deficiency). It is also known as a peroxisomal bifunctional enzyme deficiency or bifunctional enzyme deficiency.

This condition begins in gestational weeks of development. The children born with this disorder have weak muscle tone and suffer from seizures often. In most cases, they do not acquire any developmental skills or milestones. Most children suffering from D-bifunctional protein deficiency do not survive beyond two years. Its incidence is rare and is estimated to affect 1 in 100000 newborns. In minor cases, the individuals may survive, but they may have unusual facial features. There is no cure for DBP deficiency.

What Causes D-Bifunctional Protein Deficiency?

D-bifunctional protein deficiency is an autosomal recessive disorder. The autosomal recessive disorder occurs when two copies of an abnormal gene are present in the affected individual. In this, the parents of the affected individual do not show any symptoms. In this disorder, mutation of the HSD17B4 gene is present. This gene helps in the production of D-bifunctional protein.

Any mutation in this gene can significantly affect the structure of the D-bifunctional protein and its functions. Either one or both domains that carry out this protein's enzymatic activity can be affected. It can cause the accumulation of fatty acids. The accumulation of fatty acids may lead to the breakdown of the myelin sheath (the covering that protects nerves and helps in the conduction of impulses) and may cause improper brain development. But the exact cause of specific neurological and non-neurological abnormalities in DBP deficiency is unclear.

How Is D-Bifunctional Protein Deficiency Classified?

Based on the severity of mutation, DBP deficiency is classified into three types;

Type 1 – Deficiency of both enzyme domains.

Type 2 – Deficiency of hydratase.

Type 3 – Deficiency of dehydrogenase.

If there is impairment in any one of the domains in the D-bifunctional protein, it can affect the fatty acid metabolism. Type 1 deficiency is the most severe, and most of the affected patients die within the first 14 months of life.

What Are the Symptoms of D-Bifunctional Protein Deficiency?

Most children suffering from DBP deficiency do not live beyond two years. Most of them do not achieve milestones and are presented with hypotonia (weak muscle tone) and seizures. There are less severe cases of DBP deficiency. In less severe cases, children may survive longer into childhood, have voluntary hand movements, and sit without support. Individuals with DBP deficiency are usually presented with the following features;

  • High forehead.

  • Hypertelorism – Widely spaced eyes.

  • The lengthened area between mouth and nose.

  • High arch hard palate.

  • Unusual space in the skull bones (fontanelles) in infants.

  • Progressive hearing loss.

  • Eye problems like cataracts, strabismus, etc.

  • Enlarged liver (hepatomegaly).

  • Brain abnormalities.

  • Delay of bone maturation.

DBP deficiency is also called a pseudo-Zellweger syndrome as most of the clinical features present in this disease are similar to Zellweger syndrome (a genetic disorder in newborns).

How to Diagnose D-Bifunctional Protein Deficiency?

The diagnosis of D-Bifunctional protein deficiency includes patient examination, laboratory tests, brain MRI (magnetic resonance imaging), and genetic testing. Clinical features like hypotonia, facial and skull abnormalities, and seizures are the main indicators of the condition.

The laboratory tests reveal increased levels of very long-chain fatty acids, bile acid intermediates, and branched fatty acids. The genetic test is mainly done to confirm the diagnosis. It can be done prenatally or after birth. In genetic testing, any variations in the gene can be identified.

The brain MRI aids in the diagnosis of D-bifunctional protein deficiency if there are no significant abnormalities in laboratory tests. The MRI findings may include polymicrogyria (presence of too many folds in the brain which is very small), pachygyria (abnormal migration of nerve cells into the developing brain and nervous system that can cause seizures), and leukoencephalopathy (a condition that affects the white matter of the brain) of cerebrum and cerebellum.

The future parents can undergo a carrier screening test if required. A carrier screening test helps determine the presence of any faulty genes that may cause disorders in the offspring. This allows them to understand the reproductive risk and will be helpful in making much-informed decisions. This is the most significant benefit of the carrier screening test for D-bifunctional protein deficiency.

What Is the Treatment for D-Bifunctional Protein Deficiency?

There is no cure for D-bifunctional protein deficiency. The treatment mainly includes controlling symptoms like seizures, improving growth and nutrition, and preventing liver disease progression. Medications for seizures and placement of a feeding tube can provide symptomatic relief and ensure nutrition.


The prognosis of D-bifunctional protein deficiency is very poor. Most of the affected individuals die before two years of age. Research is still under study to find a proper cure for this disease condition and ensure better longevity in affected individuals.

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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)


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