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D-bifunctional protein deficiency
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Reviewed April 2014
What is D-bifunctional protein deficiency?
D-bifunctional protein deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with D-bifunctional protein deficiency have weak muscle tone (hypotonia) and seizures. Most babies with this condition never acquire any developmental skills. Some may reach very early developmental milestones such as the ability to follow movement with their eyes or control their head movement, but they experience a gradual loss of these skills (developmental regression) within a few months. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with D-bifunctional protein deficiency do not survive past the age of 2. A small number of individuals with this disorder are somewhat less severely affected. They may acquire additional basic skills, such as voluntary hand movements or unsupported sitting, before experiencing developmental regression, and they may survive longer into childhood than more severely affected individuals.
Individuals with D-bifunctional protein deficiency may have unusual facial features, including a high forehead, widely spaced eyes (hypertelorism), a lengthened area between the nose and mouth (philtrum), and a high arch of the hard palate at the roof of the mouth. Affected infants may also have an unusually large space between the bones of the skull (fontanel). An enlarged liver (hepatomegaly) occurs in about half of affected individuals. Because these features are similar to those of another disorder called Zellweger syndrome (part of a group of disorders called the Zellweger spectrum), D-bifunctional protein deficiency is sometimes called pseudo-Zellweger syndrome.
Read more about Zellweger spectrum.
How common is D-bifunctional protein deficiency?
D-bifunctional protein deficiency is estimated to affect 1 in 100,000 newborns.
What genes are related to D-bifunctional protein deficiency?
D-bifunctional protein deficiency is caused by mutations in the HSD17B4 gene. The protein produced from this gene (D-bifunctional protein) is an enzyme, which means that it helps specific biochemical reactions to take place. The D-bifunctional protein is found in sac-like cell structures (organelles) called peroxisomes, which contain a variety of enzymes that break down many different substances. The D-bifunctional protein is involved in the breakdown of certain molecules called fatty acids. The protein has two separate regions (domains) with enzyme activity, called the hydratase and dehydrogenase domains. These domains help carry out the second and third steps, respectively, of a process called the peroxisomal fatty acid beta-oxidation pathway. This process shortens the fatty acid molecules by two carbon atoms at a time until the fatty acids are converted to a molecule called acetyl-CoA, which is transported out of the peroxisomes for reuse by the cell.
HSD17B4 gene mutations that cause D-bifunctional protein deficiency can affect one or both of the protein's functions; however, this distinction does not seem to affect the severity or features of the disorder. Impairment of one or both of the protein's enzymatic activities prevents the D-bifunctional protein from breaking down fatty acids efficiently. As a result, these fatty acids accumulate in the body. It is unclear how fatty acid accumulation leads to the specific neurological and non-neurological features of D-bifunctional protein deficiency. However, the accumulation may result in abnormal development of the brain and the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to a loss of myelin-containing tissue (white matter) in the brain and spinal cord; loss of white matter is described as leukodystrophy. Abnormal brain development and leukodystrophy likely underlie the neurological abnormalities that occur in D-bifunctional protein deficiency.
Read more about the HSD17B4 gene.
How do people inherit D-bifunctional protein deficiency?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about diagnosis or management of D-bifunctional protein deficiency?
These resources address the diagnosis or management of D-bifunctional protein deficiency and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about D-bifunctional protein deficiency?
You may find the following resources about D-bifunctional protein deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for D-bifunctional protein deficiency?
What if I still have specific questions about D-bifunctional protein deficiency?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding D-bifunctional protein deficiency?
acids ; autosomal ; autosomal recessive ; breakdown ; cell ; CoA ; deficiency ; dehydrogenase ; enzyme ; epilepsy ; fatty acids ; gene ; hypertelorism ; hypotonia ; inherited ; leukodystrophy ; molecule ; muscle tone ; nervous system ; neurological ; oxidation ; palate ; peroxisomes ; philtrum ; protein ; recessive ; regression ; spectrum ; syndrome ; tissue ; white matter
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (4 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.