Some conditions are associated with both symmetrical and asymmetrical growth restriction. Asymmetrical
Asymmetrical IUGR accounts for 70-80% of all IUGR cases. In asymmetrical IUGR, there is decreased oxygen or nutrient supply to the fetus during the third trimester of pregnancy due to placental insufficiency. This type of IUGR is sometimes called "head sparing" because brain growth is typically less affected, resulting in a relatively normal head circumference in these children. Because of decreased oxygen supply to the fetus, blood is diverted to the vital organs, such as the brain and heart. As a result, blood flow to other organs - including liver, muscle, and fat - is decreased. This causes abdominal circumference in these children to be decreased.A lack of subcutaneous fat leads to a thin and small body out of proportion with the liver. Normally at birth the brain of the fetus is 3 times the weight of its liver. In IUGR, it becomes 5-6 times. In these cases, the embryo/fetus has grown normally for the first two trimesters but encounters difficulties in the third, sometimes secondary to complications such as pre-eclampsia. Other symptoms than the disproportion include dry, peeling skin and an overly-thin umbilical cord. The baby is at increased risk of hypoxia and hypoglycemia. This type of IUGR is most commonly caused by extrinsic factors that affect the fetus at later gestational ages.
The active substance in Libmeldy is stem cells, (CD34+ cells), derived from the patient’s own bone marrow or blood, that have been modified to contain a copy of the gene to make ARSA and can divide to produce other sorts of blood cells. Atidarsagene autotemcel
A gene therapy called atidarsagene autotemcel was approved for medical use in the European Union in December 2020 and is sold under the trade name Libmeldy. The indication is for use in children with the late infantile or early juvenile forms of MLD who have been identified as carriers of the defective gene but have not yet developed symptoms. It is also indicated in children who have been diagnosed with the early juvenile form who have started developing symptoms but still have the ability to walk independently and before the onset of cognitive decline.In the United States, an Investigational New Drug application for atidarsagene autotemcel was accepted by the Food and Drug Administration in late 2020. Research directions
Several therapy options are currently being investigated using clinical trials primarily in late infantile patients. These therapies include gene therapy, enzyme replacement therapy (ERT), substrate reduction therapy (SRT), and potentially enzyme enhancement therapy (EET). In addition to the clinical trials, there are several other pre-clinical gene therapy research projects underway. Epidemiology
The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide.