Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02298686 |
| Other study ID # |
BSF01-2014 |
| 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Withdrawn |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 ear-ly and sensitive diagnosis of Sanfilippo
Disease Type A-B-C-D from blood (plasma)
Description:
The Mucopolysaccharidoses (MPS Disorders) are a group of rare genetic disorders caused by the
deficiency of one of the lysosomal enzymes, resulting in an inability to metabolize complex
carbohydrates (mucopolysaccharides) into simpler molecules. High concentrations of
mucopolysaccharides in the cells of the central nervous system, including the brain, cause
the neu-rological and developmental deficits that accompany these disorders.
Lysosomal enzymes are found in the lysosome, a very small membrane-contained body (organelle)
found in the cytoplasm of most cells. The lysosome is often called the "waste disposal plant"
of the cell. The accumulation of these large, undegraded mucopolysaccharides in the cells of
the body is the cause of a number of physical symptoms and abnormalities.
MPS-III (Sanfilippo Syndrome) is one of seven MPS Disorders. It is an inborn error of
metabolism that is transmitted as an autosomal recessive genetic disorder. MPS-lll has been
categorized into four subtypes: MPS-III Type A, MPS-III Type B, MPS-III Type C, and MPS-III
Type D depending on the gene defect (MPS3A - SGSH gene, MPS3B - NAGLU gene, MPS3C - HGSNAT,
MPS3D - GNS gene). All types are associated with some degree of mental deterioration, but the
severity depends on the particular type of MPS-lll. Several physical defects may be present,
and the severity of these defects varies with the type of MPS-III. In the case of each type
of MPS-III, abnormal amounts of a specific, chemically complex molecule is excreted in the
urine. The excreted chemical is the same for each of the four types of MPS-III, since the
defective gene involves a different step, and thus a different enzyme, in the deconstruction
of the same mucopolysaccharide. By testing for one or another of these enzymes, the variant
type may be readily identified.
Symptoms Patients with Sanfilippo Syndrome (MPS Type III) usually appear normal at birth, but
mental retardation and developmental delay is usually evident by age 3-5 years. Mental and
motor development reaches a peak by 3-6 years of age after which behavioral disturbances and
intellectual decline usually occur. However, hyperactivity and irritability may become
obvious earlier.
The following symptoms are usually apparent by approximately age 10: neurological deficits
and signs, wobbly and erratic gait and difficulty walking (ataxia), hyperactivity
(hyperkinetic syndrome), mental retardation, stiff joints, hernias, enlarged liver and/or
spleen (hepatosplenomegaly).Growth is usually minimally affected; the head may be enlarged,
and abnormal hairiness (hirsutism) may occur. Mild coarsening of facial features also
characterizes this disorder. In some cases deafness may also occur.
Causes All four varieties of MPS-III are autosomal recessive genetic disorders.
The gene abnormalities associated with MSS-IIIA, MPS-IIIB, MPS-IIIC and MPS-IIID have been
identified. The Gene Map Loci are as follows:
MPS-IIIA --------- 17q25.3; SGSH gene
MPS-IIIB --------- 17q21.2; NAGLU gene
MPS-IIIC --------- 8p11.21; HGSNAT gene
MPS-IIID --------- 12q14.3; GNS gene
Genetic diseases are determined by the combination of genes for a particular trait that are
on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the
same trait from each parent. If an individual receives one normal gene and one gene for the
disease, the person will be a carrier for the disease, but usually will not show symptoms.
The risk for two carrier parents to both pass the defective gene and, therefore, have an
affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the
parents is 50% with each pregnancy. The chance for a child to receive normal genes from both
parents and be genetically normal for that particular trait is 25%. The risk is the same for
males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous)
have a higher chance than unrelated parents to both carry the same abnormal gene, which
increases the risk to have children with a recessive genetic disorder.
