Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT03284658 |
| Other study ID # |
BTY 06-2018 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 20, 2018 |
| Est. completion date |
February 28, 2021 |
Study information
| Verified date |
February 2023 |
| Source |
CENTOGENE GmbH Rostock |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Development of a new MS-based biomarker for the early and sensitive diagnosis of Tyrosinemia
type 1 from blood (plasma)
Description:
Hereditary Tyrosinemia type 1 (HT-1) is a rare genetic disorder in which the newborn child
lacks the ability to break down the amino acid tyrosine. As a result of this deficiency,
toxic sub-stances build up in the blood and can cause liver failure, kidney dysfunction and
neurological problems. There are two different forms of the disease - acute and chronic. The
acute form is most common.
Worldwide, Tyrosinemia type 1 affects about one newborn child in 100,000, although
geo-graphical variation is seen.
Tyrosinemia type 1 is hereditary. The disorder is caused by a defect in the gene coding for
the enzyme responsible for breaking down tyrosine. For a child to be affected by the disease,
both parents have to carry a defective gene. The risk of being born with Tyrosinemia type 1,
i.e. receiving both genes from the parents, is thus 25%.
Children with Tyrosinemia type 1 can display symptoms such as failure to gain weight and grow
at the expected rate, diarrhea, vomiting, enlarged liver, liver failure, accumulation of
fluid in the peritoneal cavity, kidney failure, softening of the bones (rickets) and liver
tumors.
The acute form usually appears in the first few months of life. The child has a slow weight
gain plus fever, diarrhea, blood in the feces and vomiting. The liver is enlarged and
yellowing of the skin and the whites of the eyes (jaundice) with an increased tendency to
bleed (particularly nosebleeds) may be evident. The spleen and abdomen can also be enlarged
and the legs swollen. Without treatment, liver failure and clotting problems can arise.
Children with the chronic form of Tyrosinemia type 1 develop symptoms gradually. The child
can suffer from enlarged liver, distended abdomen (due to enlarged liver and spleen, acites
and excessive fluids), changes in skeleton, and liver and kidney failure. Symptoms such as
abdominal pain, damage to the peripheral nerves and high blood pressure appear. In addition,
symptoms common in acute intermittent porphyria can also occur. If the child is not treated,
it will develop liver failure and liver tumors.
The condition is also referred to as hepatorenal Tyrosinemia, and is the most critical
variant of Tyrosinemia. The main function of the FAH gene is to regulate the production of
the enzyme fumarylacetoacetase that is required to break down or metabolize amino acid
tyrosine. The mutations of FAH gene leads to a deficiency of the enzyme fumarylacetoacetase,
which then leads to a failure in breaking down tyrosine.
Tyrosinemia type 1 is suspected on the basis of clinical presentation. Diagnostic
investigations include analyses of amino acids, succinylacetone and alpha-fetoprotein.
Today, the condition can be treated by diet, medication and liver transplantation. Liver
trans-plantation was once the only treatment, but since a new drug was introduced in 1991,
survival has increased significantly. Nevertheless, diet and special protein replacements
remain an important part of life-long treatment.
New methods, like mass-spectrometry give a good chance to characterize specific metabolic
alterations in the blood (plasma) of affected patients that allow diagnosing in the future
the dis-ease earlier, with a higher sensitivity and specificity.
Therefore it is the goal of the study to identify and validate a new biochemical marker from
the plasma of the affected patients helping to benefit other patients by an early diagnose
and thereby with an earlier treatment.
