National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

D-bifunctional protein deficiency


Other Names:
DBP deficiency; Peroxisomal bifunctional enzyme deficiency; PBFE deficiency; DBP deficiency; Peroxisomal bifunctional enzyme deficiency; PBFE deficiency; 17-BETA-HYDROXYSTEROID DEHYDROGENASE IV DEFICIENCY; Bifunctional enzyme deficiency See More
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D-bifunctional protein deficiency (DBP deficiency) is a genetic disorder that affects the ability of the body to effectively break down fat from our diet. It is typically characterized by hypotonia (low muscle tone) and seizures in the newborn period. Other symptoms include unusual facial features and an enlarged liver (hepatomegaly). Most babies with this condition never gain any developmental skills and do not survive past the age of 2. DBP deficiency is caused by mutations in the HSD17B4 gene and is inherited in an autosomal recessive manner.[1]

Some researchers have suggested classifying DBP deficiency into three subtypes, depending on how severely the mutation in the HSD17B4 gene affects the function of the gene and the protein that it codes for. Almost all individuals with types I, II, and III have similar signs and symptoms. A fourth subtype has additionally been proposed for individuals that have less severe symptoms.[2]

While there is no cure for DBP deficiency, treatment is focused on improving nutrition and growth, controlling symptoms, and limiting the progression of liver disease.[3]
Last updated: 12/6/2016
The signs and symptoms of DBP deficiency are typically very severe, with almost all children presenting with hypotonia (low muscle tone) and seizures in the first month of life. Other issues that might be present in children with DPB deficiency include:[4][1]
  • Eye problems (nystagmus, strabismus, failure to focus on objects, optic nerve atrophy, cataracts, and/or progressive vision loss)
  • Progressive hearing loss
  • Failure to achieve or loss of developmental milestones 
  • Distinct facial features (high forehead, high arched roof of the mouth (palate), enlarged soft spot (fontanelle), long philtrum, epicanthal folds, widely spaced eyes (hypertelorism), macrocephaly, retrognathia, and low-set ears)
  • Enlarged liver (hepatomegaly) 
  • Brain abnormalities (polymicrogyria, damage to the protective covering of the brain (demyelination))
Last updated: 12/6/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
1%-4% of people have these symptoms
Cerebral hypoplasia
Small cerebrum
Underdeveloped cerebrum
[ more ] 		0006872
Decreased nerve conduction velocity 0000762
Percent of people who have these symptoms is not available through HPO
Abnormal facial shape
Unusual facial appearance
0001999
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum
[ more ] 		0007360
Autosomal recessive inheritance 0000007
Bile duct proliferation 0001408
Calcific stippling 0002832
Cerebral dysmyelination 0007266
Cholestasis
Slowed or blocked flow of bile from liver
0001396
Corpus callosum atrophy 0007371
Cortical dysplasia 0002539
Decreased muscle mass 0003199
Delayed cranial suture closure 0000270
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development
[ more ] 		0002750
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Dolichocephaly
Long, narrow head
Tall and narrow skull
[ more ] 		0000268
Elevated hepatic transaminase
High liver enzymes
0002910
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Feeding difficulties in infancy 0008872
Fetal ascites 0001791
Frontal bossing 0002007
Generalized cerebral atrophy/hypoplasia
Generalized cerebral degeneration/underdevelopment
0007058
Gliosis 0002171
Global developmental delay 0001263
Hammertoe
Hammer toe
Hammertoes
[ more ] 		0001765
Hepatic steatosis
Fatty infiltration of liver
Fatty liver
[ more ] 		0001397
Hepatomegaly
Enlarged liver
0002240
High forehead 0000348
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Large fontanelles
Wide fontanelles
0000239
Long philtrum 0000343
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Osteopenia 0000938
Pectus excavatum
Funnel chest
0000767
Polyhydramnios
High levels of amniotic fluid
0001561
Polymicrogyria
More grooves in brain
0002126
Primary adrenal insufficiency 0008207
Renal cyst
Kidney cyst
0000107
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw
[ more ] 		0000278
Scaphocephaly 0030799
Seizure 0001250
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand
[ more ] 		0001171
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot
[ more ] 		0001762
Thoracic hypoplasia
Small chest
Small thorax
[ more ] 		0005257
Undetectable electroretinogram 0000550
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Ventriculomegaly 0002119
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
Visual loss
Loss of vision
Vision loss
[ more ] 		0000572
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Last updated: 7/1/2020
DBP deficiency is caused by mutations in the HSD17B4 gene. This gene codes for a special type of protein, called D-bifunctional protein, which is an enzyme (helps biochemical reactions take place). The D-bifunctional protein is found in structures within our cells called peroxisomes, which contain several different enzymes that break down different substances. The D-bifunctional protein is involved in breaking down products of fats in our diet called fatty acids. The protein has two separate parts with different enzyme activity, called hydratase and dehydrogenase domains. These domains help carry out the second and third steps of a metabolic process called the peroxisomal fatty acid beta-oxidation pathway. This pathway breaks down fatty acid molecules so they can be transported out of the peroxisomes for reuse by the cell.[1]

Mutations in the HSD17B4 gene that cause D-bifunctional protein deficiency can affect one or both of the protein's functions. Although this does not seem to affect the severity of the symptoms of the disorder, the condition may be grouped into three types based on which enzyme(s) is/are deficient:[1][2]
  • Type 1 - deficiency of both enzymes
  • Type 2 - deficiency of hydratase
  • Type 3 - deficiency of dehydrogenase
Impairment of one or both of the protein's functions prevents the ability of the protein from breaking down fatty acids properly, resulting in a buildup of fatty acids in the body. It is not clear how the fatty acid buildup leads to the symptoms of this disorder.[1] 

Last updated: 12/6/2016
DBP deficiency can be diagnosed based on lab results showing increased levels of the following: (1) very long-chain fatty acids; (2) α-methyl-branched fatty acids such as pristanic acid and its precursor phytanic acid; and (3) Bile acid intermediates dihydroxycholestanoic acid (DHCA) and trihydroxycholestanoic acid (THCA). Genetic testing may be useful to confirm the diagnosis.[4][3]
Last updated: 12/6/2016

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to D-bifunctional protein deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on D-bifunctional protein deficiency. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss D-bifunctional protein deficiency. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. D-bifunctional protein deficiency. Genetics Home Reference. April, 2014; http://ghr.nlm.nih.gov/condition/d-bifunctional-protein-deficiency. Accessed 12/6/2016.
  2. McKusick, VA. D-BIFUNCTIONAL PROTEIN DEFICIENCY. In: Kniffin, CL. OMIM. 6/16/2014; http://www.omim.org/entry/261515. Accessed 12/6/2016.
  3. João Nascimento, Céu Mota, MDb, Lúcia Lacerda, Sara Pacheco, Rui Chorão, Esmeralda Martins, Cristina Garrido. D-Bifunctional Protein Deficiency: A Cause of Neonatal Onset Seizures and Hypotonia. Pediatric Neurology. January 24, 2015; 52(5):539-543. https://www.ncbi.nlm.nih.gov/pubmed/25882080.
  4. Ferdinandusse S, Denis S, Mooyer PAW, Dekker C, Duran M, Sorrani-Lunsing RJ et al. Clinical and Biochemical Spectrum of D-Bifunctional Protein Deficiency. Ann Neurol. 2006; 59(1):92-104. https://www.ncbi.nlm.nih.gov/pubmed/16278854.