D-bifunctional Protein Deficiency

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Mutations in the HSD17B4 gene cause this condition, as this gene should produce D-Bifunctional Protein. D-Bifunctional protein is involved in the breakdown of fatty acids; without it, these accumulate. These fatty acids may cause abnormal brain development and the breakdown of myelin (white matter), causing the symptoms described.

These features are similar to Zellweger syndrome, the condition is sometimes referred to as Pseudo-Zellweger syndrome.

Whilst we do not know exactly how many people have this disorder, it is estimated to affect 1 in every 100,000 newborns.

This condition, beginning in infancy, causes neurodegeneration, with most babies never acquiring developmental skills. Those who learn basic skills such as the ability to control head movement or follow movement with their eyes will see these skills deteriorate within a few month. Some who are less severely affected may be able to move their hands voluntarily or sit unsupported before experiencing developmental regression.

Hypotonia (a weak muscle tone) and seizures are common, and worsen over time. Hyperreflexia (exaggerated reflex responses) occurs in later stages, alongside increased muscle tone and a loss of vision and hearing. Most affected children do not survive past the age of two, some who are not so severely affected may live longer into childhood.

Around half of those affected will suffer from hepatomegaly (an enlarged liver). Some have macrocephaly (an enlarged head), abnormally large fontanelles (the spaces between the bones in the skull as an infant develops; colloquially known as ‘soft spots’), as well as unusual facial features such as a high forehead, retrognathism, low set ears and widely spaced eyes.

Diagnosis may be determined by the acknowledgement of physical symptoms, a range of specialised tests, and a patient and family history. Genetic testing can confirm diagnosis.

Research is ongoing into the use of Whole Genome Sequencing to diagnose D-bifunctional Protein Deficiency.

There is no cure for this disorder. Treatment is currently based on the individual symptoms which are present, avoiding complications, improving nutrition, limiting progression, and providing support for your child and your family as a whole.

Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes.

The word mutation means a change or error in the genetic instruction.

We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instruction that determines characteristics, which are a combination of the parents.

This is an inherited condition. There is nothing that could have been done to prevent your baby from having this condition.

Everyone has a pair of genes that make D-bifunctional Protein. In children with this disorder, neither of these genes works correctly. These children inherit one non-working gene from each parent.

Parents of children with this disorder are termed as carriers of the condition. Carriers do not have the disorder because the other gene of this pair is working correctly.

When both parents are carriers, in each pregnancy the risk to the baby is as follows:

• There is a 25% chance (1 in 4) of the baby having the disorder.
• There is a 50% chance (1 in 2) for the baby to be a carrier of the disorder.
• There is a 25% chance (1 in 4) for the baby to have two working genes and neither have the disorder nor be a carrier

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: PPX015].