The classic MSUD would present the earliest among neonates from first to second week of life. They may present with lethargy, vomiting, irritability, abnormal movements, poor feeding habits and poor weight gain which are eminently the offshoot of the neurological effects of leucine accumulation in the brain and nerves .
The urine may give out its characteristic dark color as isoleucine is passed out unscathed by the enzymes that metabolizes it. The isoleucine build up may present in infants as a sweet smelling perspiration and urine. The metabolic crisis in older children may be exemplified by failure to feed and psychological stresses to the child, consequently due to the leucine, valine and isoleucine accretion from exogenous and dietary sources.
Comatose patients are portrayed by severe MSUD cases with brain edema and irreversible neurologic impairments due to ketotic hypoglycemia and the amino acid accumulation and in the neurons which may culminate into death.
In prenatal phase, genetic studies derived from amniotic fluid and chorionic villus may already demonstrate an accumulation of the branched-chain amino acids which heralds the diagnosis of MSUD . At birth, routine newborn screening detects may demonstrate an increased Fisher ratio of leucine and isoleucine which is suggestive of the disease.
Confirmatory tests for the newborn screening may be opted beyond the sixth day of life by elucidating the increases concentration of alloisoleucine in the plasma as marker of a non-carboxylated isoleucine metabolite . Urine tests make use of a combination of gas chromatography and mass spectrometry to identify organic acids like pyruvate, lactate and ketoglutarate which are known end metabolites of leucine and isoleucine catalysis.
Dietary support remains a cornerstone in the management of MSUD. Patients with this genetic disorder may be given protein free diet to avert the unwanted deposition of leucine, isoleucine and valine in the plasma. Parenteral nutrition may be administered protein-free with sugar and fats to support growth and energy requirements.
Metabolic decompensation in infants may require aggressive glucose infusion up to 5-8 mg/kg/min to promote anabolism of proteins. In severe metabolic crisis, peritoneal dialysis may be a recourse to eliminate the toxic metabolites in the system. Infants may benefit from man-made milk formula devoid of the three amino acids. Liver transplants to infant patients have shown promising results in MSUD treatment .
Patients with the successful liver transplant have averted complication of brain retardation but will not permanently disrupt all metabolic decompensation in MSUD . Patients in remission must follow a strict dietary regimen with close monitoring of the amino acid levels in the blood stream.
MSUD is a metabolic disorder with life threatening consequences if no medical attention is offered to the child. Even with adequate treatment, accumulation of the same amino acids as a result of high dietary consumption, acquired illnesses and severe stress may mimic the same metabolic consequences as that of a fulminant MSUD case. Strict dietary control and amino acid assay monitoring may be imperative for these patients .
It is medically possible for an MSUD infant to grow into a normal adult with adequate dietary counselling and medical therapy.
The unabated accumulation of leucine in the plasma can be attributed to the neurologic complications of delayed psycho-motor development and mental retardation in children. Metabolite accumulation in the brain may cause chronic seizures, brain edema, coma and death. In patients diagnosed with MSUD and on active therapy, a metabolic crisis of lethargy, fatigue, and seizure may occur during surges of amino acid accumulation from internal and exogenous sources.
Maple Syrup Urine Disease is inherited via a recessive gene from both parents. This consequently means that both parents are neither suffering from the disease but are genetically carriers of the trait. The more common forms of MSUD are the classic form which is eminent at birth and those that are latent which manifest clinically late in childhood but can still assert the same medical complications and developmental delays if left untreated.
In has been recorded, that 1 out of 180,000 birth in the United States has MSUD . However, there are increased cases among inbred populations like the Mennonites in Pennsylvania where the ratio is 1 case per 176 births. MSUD has a greater penetrance in a genetic population with close consanguinity. It is also noted that Maple Syrup Urine Disease has been seen in all ethnicity worldwide.
In the absence of the branched-chain α-ketoacid dehydrogenase that catalyzes the decarboxylation of the ketoacids of leucine, isoleucine and valine, this three amino acids remain free in the blood stream instead of being converted to the helpful energy compounds like acetyl CoA, Succinyl CoA and acetoacetate.
The excessive accumulation of Leucine in the plasma causes the neurologic defects observable in patients because it is readily transported through the blood brain barrier where it is metabolized to glutamine. The characteristic odor in MSUD is caused by the accumulation of the amino acid isoleucine in the plasma. The branched-chain α-ketoacid dehydrogenase complex found in the inner mitochondrial membrane has 3 variations of mutations (E1, E2, and E3 respectively). Genotypic to phenotypic expressions remains insignificant save for the E2 variants which are responsive to thiamine supplementation .
The E3 variant however, has an associated additional deficiency in pyruvate and α-ketoglutarate dehydrogenase .
Maple Syrup Urine Disease can only be prevented with proper genetic counselling to parents with off-springs suffering from the disease. This also covers those in the population and family gene pool which may carry the recessive trait in their genes. Genetic study of the prenatal amniotic fluid may be in place for these cases.
Children born with high suspicion of MSUD should undergo confirmatory tests to prevent future problems.
Maple Syrup Urine Disease or MSUD is a hereditary genetic defect in the breakdown of leucine, isoleucine and valine amino acids due to the absence of the catabolic enzyme branched-chain α-ketoacid dehydrogenase. This disease is coined maple syrup because of the characteristic odor and dark color appearance of the urine of afflicted infants resembling that of burnt sugar or maple syrup .
This genetic defect appears benign at birth but may prove to be seriously complicated if left unchecked. Because of this, Maple Syrup Urine Disease is actively being included in the routine newborn screening in all infants for early detection and intervention. Untreated MSUD in infants may result to poor feeding, vomiting, lethargy and psycho-motor developmental delays while chronic complicated forms of MSUD may lead to seizure, coma and death.
People must embrace the idea that the complications of MSUD as a genetic disease may be averted effectively if one submits the infant for a complete newborn screening work-up. Mental retardation worldwide has been significantly lowered due to this innovation in neonatal pediatrics. Marriage counselling must include genetic diseases in the family to prevent the expression of this recessive trait.