Congenital Bile Acid Synthesis Defect Type 1

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This condition is caused by a fault in the HSD3B7 gene. The gene provides instructions for your body to produce an enzyme called 3-beta-hydroxy-delta-5-C27 steroid oxidoreductase (HSD3B7).

This enzyme is needed by your body to help the cells in your liver to produce bile acids from cholesterol. Your body then sends these bile acids from the liver to the intestine to help you to break down fats.

Bile acids are compounds found in the liver. They are needed for the following reasons:

• To promote the flow and the excretion of a digestive fluid called bile
• To help your body to absorb fat and fat-soluble vitamins (e.g. vitamins A, D, E, and K)

A fault in the HSD3B7 gene means that not enough of the enzyme is produced. As a result, your body is unable to carry out the necessary chemical reactions to produce bile acids. This means that your body will instead produce bile acids that your body cannot transport out of the liver. This causes fats and cholesterol to accumulate in the liver and also means that vitamins cannot be absorbed properly.

This condition belongs to a group known as the congenital defects of bile acid synthesis. It is the most common of these conditions. We do not know exactly how many people are affected by this condition. However, we do know that collectively, this group of conditions affect approximately 1 in 50,000. They affect males and females equally, and the prevalence is equal across all races.

Signs and symptoms can vary in severity and it can affect individuals differently. You are most likely to notice symptoms develop during the first few weeks of life. However, they can also begin later and into adulthood. Generally, this condition is characterised by:

• The reduction or complete absence of bile flow (cholestasis)
• The inability to absorb fats and fat-soluble vitamins

Early symptoms include:

• Failure to grow and gain weight at the expected rate (failure to thrive)
• Yellowing of the skin and/or eyes (jaundice)
• Diarrhoea, clay coloured stools and/or fat in the stools

If left untreated, symptoms can progress to include:

• An enlarged liver (hepatomegaly)
• An enlarged spleen (splenomegaly)
• Soft and weak bones, developing due to the inability to absorb vitamin D.
• Susceptibility to bleeding, due to problems in blood clotting and coagulation
• Scar tissue replacing normal tissue in the liver (liver cirrhosis)

If this disorder is untreated, or not managed correctly it can lead to progressive liver disease and death in childhood.

In some cases, jaundice develops early in life before resolving itself. Liver disease may not occur until later in life, at which point this condition may be diagnosed

This condition is diagnosed using specialised blood tests and analysis of the urine. If there is a known family history of this condition, it may be diagnosed before birth. If a newborn is suspected of having the condition, urine analysis can provide a diagnosis within days.

This condition can be treated using cholic acid which is taken orally. This therapy will gradually resolve symptoms and prevent it from progressing. If this condition is treated early, the prognosis is excellent.

Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes. We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.

In most cases, this is an inherited condition. However, sometimes it can occur sporadically. There is nothing that could have been done to prevent it.

Everyone has a pair of genes that are needed to make the HSD3B7 enzyme. In children with this condition, neither of these genes works correctly. These children inherit one non-working gene from each parent.

Parents of children with this condition are known as carriers. Carriers do not have the condition 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:

• 25% chance (1 in 4) of developing the condition
• 50% chance (1 in 2) for the baby to be a carrier of the condition.
• 25% chance (1 in 4) for the baby to have two working genes and neither have the condition  or be a carrier

References are available on request. Please contact us by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org [Resource Library No: CST013].