Maple syrup urine disease (MSUD) is an aminoacidopathy secondary to an enzyme defect in the catabolic pathway of the branched chain amino acids such as leucine, isoleucine and valine. Accumulation of these three and their corresponding keto acids leads to encephalopathy and progressive neuro degradation in treated infants. Early diagnosis and dietary intervention prevents complications and may allow for normal intellectual development. Consequently maple syrup disease urine disease has been added to many new born screening programs, and preliminary results indicates that asymptomatic newborn with maple syrup urine disease have a better outcome compared with infants who are diagnosed after they become symptomatic.
In 1954, Menkes et al reported a family in which four infants died within the first three months of their lives because of a neurodegradative disorder. The urine of these infants have the odour resembling maple syrup (burned sugar), therefore these disease was called maple sugar urine disease and later maple syrup urine disease. In the following years, Dancil et al identified the pathogenic compounds as branched chained amino acids and their corresponding alpha-keto acids. In 1960, Dancil et al demonstrated that the enzymatic defect in maple syrup urine disease (MSUD) was at the level of decarboxylation of the branched chain amino acids. Synderman et al initiated the first successful dietary treatment for MSUD by restricting intake of branched chain amino acids. In 1971, Scriver et al reported the first case of thiamine responsive MSUD. The branched chain alpha-keto acid dehydrogense (BCKD) complex was purified and characterized in 1978.
PATHPHYSIOLOGY OF MAPLE SYRUP URINE DISEASE
Maple syrup urine disease (MSUD) is caused by a deficiency of the branched chain alpha-keto acid dehydrogenases (BCKD) complex, which catalyses the decarboxylation of alpha-keto acids of leucine, isoleucine and valine to their repective branched chain acyl-coAs. These are further metabolized to yield acetyl coA, acetoacetate and succinyl coA. The BCKD complex which is associated with the inner mitochondrial membrane has three different catalytic components (i.e. E1, E2, E3) and two associated regulatory enzymes (i.e. BCKD phosphatase and BCKD kinas) in addition, the E1 component consists of two distinct subunits (i.e. E1 alpha and E1 beta) that form the alpha-2-beta-2 heterotetramer. The E3 component is associated with two additional alpha-keto acid dehydrogenase complexes, namely pyruvate dehydrogenase and alpha-keto glutarate dehydrogenases. Mutation in E1, E2 or E3 causes maple syrup urine disease (MSUD), no good genotype-phenotype correlation between molecular and clinical phenotype Is known, with the exemption of mutation in E2 which causes thymine responsive MSUD. The mutation in E3 causes additional deficiency of pyruvate and alpha-keto gluterate dehydrogenases. Mutation in regulatory enzymes have not been reported.
Accumulation of leucine in particular causes neurological symptoms, whereas elevation of plasma isoleucine is associated with maple syrup odour. Leucine is rapidly transported across the blood-brain barrier as it is metabolized to presumably yield glutamine.
MAPLE SYRUP URINE DISEASE (MSUD)
Maple syrup urine disease is a disorder in which the body cannot break down certain arts of proteins. The urine of people with this condition can smell like male syrup.
CAUSES
Maple syrup urine disease (MSUD) is inherited, meaning it is passed down through families. It is caused by a defect in 1 of 3 genes. People with this condition cannot break down the amino acid leucine, isoleucine and valine. This leads to a buildup of this chemicals in the blood. In most severe form, maple syrup urine disease can damage the brain during times of physical stress (such as infection, fever, or eating for a long time). Some types of MSUD are mild or come and go. Even in the mildest form, repeated periods of physical stress can cause mental disabilities and high level of leucine to build up.
Maple syrup urine disease is often classified by its pattern of sign and symptoms. The most common and sever form of the disease is the classic type, which becomes apparent soon after birth. Variant form of disorder become apparent later in infancy or childhood and are typically milder, but they still lead to delayed development and other health problems if not treated.
Maple syrup urine disease (MSUD) is also called branched-chain keto aciduria, it is an autosomal recessive metabolic disorder affecting the branched chain amino acids. It is one type of organic academia. The condition gets its name from the distinctive sweet odour of affected urine, particularly prior to diagnosis and during times of acute illness.
INFANTS WITH MAPLE SYRUP URINE DISEASE
Infants with this disease seem healthy at birth but quickly deteriorate, often with severe brain damage which may be permanent. Death often occurs during the first 5 months in severe cases of the disease when left untreated. The symptom of maple syrup urine disease may also present later depending on the severity of the disease. Untreated in older individuals, and times of metabolic crisis, symptoms of the condition include uncharacteristically, inappropriate, external or erratic behaviours and moods, hallucination, anorexia, weght los, anemia, diarrhea, vomiting, atraxia seizure, hypoglycemia, keto acidosis, opiathotorius, pancreatitis, rapid neurological decline and coma. Without prompt treatment, they would likey die from cerebral oedema.
Additionally, maple syrup urine disease patients often experience an abnormal course of disease in simple infections that become increasingly severe and can permanently damage in more rare cases, concomitant osteoporosis may also appear in these patients.
DIAGNOSIS
Prior to the easy availability f plasma amino acid measurement, diagnosis was commonly made based on suggestive symptoms and odour. Affected individuals are now often identified with characteristic elevation in plasma amino acids which do not habe the characteristic odour. The compound responsible for odour is sotolon (sometimes spelled sotolone).
PREVENTION
There are no methods for preventing the manifestation of the pathology of maple syrup urine disease, in infants with two defective copies of the branched chain alpha-keto acid dehydrogenase (BCKD) gene. However, genetic councellors may consult with couple of screens for the disease via DNA testing. DNA testing is also available for identify the disease in an inborn child in the womb.
