Maple Syrup Urine Disease (MSUD)
MSUD is inherited in an autosomal recessive pattern. Normally a person has two functional BCKDHA, BCKDHB and DBT genes. In people with MSUD, both copies of one of these genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with MSUD typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
The severity and age of onset of symptoms in people with MSUD is variable. The earwax and urine of babies with MSUD has an odor of maple syrup. The symptoms of the classic type begin in the first few days to weeks of life as poor feeding, vomiting and lethargy and progress to seizures, coma and death. The intermediate type of MSUD is milder, with symptoms (including developmental delay) beginning anytime after early infancy until childhood. There is also an intermittent type. Patients with this type have completely normal leucine levels unless they are ill. The thiamine response type has symptoms similar to the intermediate type, but thiamine supplementation reduces symptoms.
- Incidence: MSUD is very rare. It occurs in less than 1 in 185,000 newborns. It is more common in the Amish and Mennonite populations.
- New York State Method of Screening (First Tier): Screening for MSUD is accomplished by measuring leucine by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: In the classic type, branched chain amino acids are not elevated until 12-24 hours of life. Therefore, a blood sample collected before 24 hours of life may be screen negative in a newborn with MSUD. Also, supplementation with total parenteral nutrition can cause a false positive screen. Newborn screening may not be able to identify the intermittent or intermediate type unless the sample is collected during a time of illness.
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen must be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for MSUD are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of MSU.
Diagnostic testing may include urine organic acid analysis, plasma amino acid analysis, and gene sequencing.
Treatment is typically dietary management including careful monitoring of leucine and supplementation with isoleucine and valine. Additional medical care, including admission to the hospital for intravenous feedings, may be required during times of illness. Liver transplant has been used as a treatment for classic cases. In some patients, thiamine supplementation allows them to eat more leucine.
Prognosis is variable, and dependent on many factors, including severity of disease and response to treatment.
Components of protein (the branched chain amino acids leucine, isoleucine and valine) are broken down as part of normal metabolism. Three genes, BCKDHA, BCKDHB and DBT provide instructions for a group of important enzymes in this process. If there are two mutations in any one of these genes, the enzymes do not function and the branched chain amino acids are not broken down. Toxic metabolites accumulate and cause symptoms.