![]() The prognosis is good if metabolic control is maintained during times of stress and any episodes of acute decompensation are immediately treated. Management of acute decompensation requires aggressive enhancement of protein anabolism which may include using glucose plus insulin, intravenous lipids, plasma amino acid monitoring, and isoleucine and valine supplements. ![]() However, they need regular review at a metabolic clinic and a management strategy to avoid acute decompensation including a high-energy, low-protein diet during illness. Patients with intermittent MSUD tolerate a normal intake of leucine and treatment is not necessary. ![]() Inheritance is autosomal recessive and genetic counseling is possible. Prenatal diagnosis is possible in families with a known disease-causing mutation. Although deficiency of the branched-chain ketoacid dehydrogenase (BCKDC) and associated elevations in the BCAAs and their ketoacids have been recognized as the cause of maple syrup urine disease (MSUD) for decades, treatment options for this disorder have been limited to dietary interventions. Differential diagnosisĭifferential diagnoses of the presenting symptoms may include other inborn errors of intermediary metabolism such as NAGS deficiency, ornithine transcarbamylase deficiency, argininosuccinic aciduria (and other urea cycle defects), neonatal glycine encephalopathy, propionic acidemia and beta-ketothiolase deficiency (see these terms). Ketonuria and gas chromatography-mass spectrometry can also identify branched-chain alpha ketoacids (BCKAs) in the urine during decompensation only. BCAA levels are usually normal or only slightly elevated, except during times of physiological stress when the biochemical profile is similar to classic MSUD. In a study of 52 individuals with classic MSUD. Intermittent MSUD may be missed on tandem mass spectrometry newborn screening. Treatment of MSUD consists primarily of a severely restricted diet to limit the intake of BCAA, with aggressive medical interventions when blood levels of BCAA. Orthotopic liver transplantation in pediatric patients with classic MSUD has been a very successful treatment. Maple Syrup Urine Disease (MSUD) is an inherited disorder so named because one of its first signs is urine that has an odor reminiscent of maple syrup. In intermittent MSUD, mutations in DBT may predominate. Mutations lead to an accumulation of BCAAs (especially leucine) and branched-chain alpha-ketoacids. The genes are BCKDHA (19q13.1-q13.2), encoding E1a, BCKDHB (6q14.1), encoding E1b, and DBT (1p31), encoding E2 respectively. MSUD is due to mutations in genes encoding 3 of the 4 subunits of the branched-chain 2-ketoacid dehydrogenase (BCKAD) complex. Intelligence and development are not usually affected by these episodes. These precipitating factors can lead to a potentially fatal episode of acute decompensation with anorexia, nausea, vomiting, lethargy, ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, acute dystonia, and choreoathetosis (in adults), that can progress to stupor, coma and cerebral edema. ![]() fasting, dehydration, fever, infections or pregnancy (in adults)). They may develop symptoms (mainly in childhood) with any catabolic stress (i.e. Unlike classic MSUD (see this term), patients with intermittent MSUD show normal growth and intellectual development during infancy and childhood. There is no data to suggest what number of patients has intermittent MSUD but it is probably underdiagnosed. We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients.īCKDHA BCKDHB DBT alloisoleucine branched-chain amino acids maple syrup urine disease newborn screening.MSUD has an estimated incidence of 1/150,000 live births. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). ![]() Clinical outcomes are generally good in patients where treatment is initiated early. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated. The disorder varies in severity and the clinical spectrum is quite broad with five recognized clinical variants that have no known association with genotype. Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by defects in the branched-chain α-ketoacid dehydrogenase complex, which results in elevations of the branched-chain amino acids (BCAAs) in plasma, α-ketoacids in urine, and production of the pathognomonic disease marker, alloisoleucine. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |