Scientists have created a new gene therapy for a debilitating genetic disorder called maple syrup urine disease (MSUD).
Recent Findings - The treatment can prevent recurrence of deadly symptoms in a cow calf born with the disease.
It prevented newborn death, normalized growth, restored coordinated expression of the affected genes and stabilized biomarkers in a calf as well as in mice.
Maple syrup urine disease (MSUD)– It is a rare genetic disorder characterized by deficiency of an enzyme complex (branched-chain alpha-keto acid dehydrogenase).
Branched-chain alpha-keto acid dehydrogenase is required to break down (metabolize) the 3 branched-chain amino acids (BCAAs) leucine, isoleucine and valine, in the body.
The result of this metabolic failure is that all 3 BCAAs, along with a number of their toxic byproducts, (specifically their respective organic acids), all accumulate abnormally.
In the classic, severe form of MSUD, plasma concentrations of the BCAAs begin to rise within a few hours of birth.
If untreated, symptoms begin to emerge, often within the first 24-48 hours of life.
Types -The classic type, intermediate type, intermittent type and possibly a thiamine-responsive type.
Cause- When a mutated form of the BCKDHA, BCKDHB or DBT gene is inherited from both parents.
Symptoms -Non-specific symptoms of increasing neurological dysfunction and include lethargy, irritability and poor feeding, soon followed by
Focal neurological signs such as abnormal movements, increasing spasticity and shortly thereafter, by seizures and deepening coma.
It is characterized by a distinctive sweet odor in the urine,reminiscent of maple syrup.
Risk level -If untreated, progressive brain damage is inevitable and death occurs usually within weeks or months.
Treatment- The disorder can be successfully managed through a specialized diet in which the three BCAAs are rigorously controlled.
However, even with treatment, patients of any age with MSUD remain at high risk for developing acute metabolic decompensation (metabolic crises).
Often triggered by infection, injury, failure to eat (fasting) or even by psychological stress.
