Maple syrup urine disease: mechanisms and management

Abstract

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. The disorder varies in severity and the clinical spectrum is quite broad with five recognized clinical variants that have no known association with genotype. 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. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. Clinical outcomes are generally good in patients where treatment is initiated early. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients.

Diálisis peritoneal en un neonato con enfermedad de la orina con olor a jarabe de arce. A propósito de un caso

“…neonatal, intermitente, intermedia, respondedora a tiamina y por deficiencia de subunidad E3. 1 La forma clásica, que es la que presentaba nuestro paciente, se suele manifestar entre el 5º y el 10º día con rechazo del alimento, somnolencia y coma. Posteriormente, aparece falta de regulación neurovegetativa, dificultad respiratoria, apnea, bradicardia, hipotermia, hipotonía axial con episodios de hipertonía, que puede llegar incluso al opistótonos.…”

“…La enfermedad de la orina con olor a jarabe de arce, también conocida como leucinosis, es una entidad autosómica recesiva producida por un error congénito en el metabolismo de tres aminoácidos esenciales de cadena ramificada: valina, leucina e isoleucina. 1 La forma neonatal de esta enfermedad se manifiesta por un cuadro de compromiso neurológico grave y progresivo, asociado a un olor peculiar de la orina, consecuencia de la eliminación del exceso de estos aminoácidos. Este olor a azúcar quemada remeda a la melaza obtenida de los arces, lo que da nombre a esta enfermedad.…”

Metformin extends the lifespan of iMSUD mice by rescuing physiologic dysfunction and modulating mechanisms of mTORC1 activation

“…This divergence at the end of the survival curve, while not statically signi cant, warrants consideration in design of different delivery strategy of metformin. In addition, iMSUD is an inborn error of metabolism in both human patient and mouse disease model (6)(7)(8)16). Considering that the chow-mediated administration of metformin could occur only after weaning (21 days of age) and the dosage of metformin can be variable based on food consumption, we next treated iMSUD mice with different doses of metformin by daily intra-peritoneal (IP) injection started at 5 days of age.…”

Silico analysis of a novel mutation c.550delT in a Chinese patient with maple syrup urine disease

“…Based on clinical presentation onset age and residual BCKD complex activity, MUSD can be divided into five forms: classic, intermediate, intermittent, thiamine responsive, and E3 deficient . Approximately 75% of affected individuals has the classic form with less than 2% residual BCKD complex activity and exhibits the most serious phenotype.…”

“…[6][7][8] Based on clinical presentation onset age and residual BCKD complex activity, MUSD can be divided into five forms: classic, intermediate, intermittent, thiamine responsive, and E3 deficient. 9,10 Approximately 75% of affected individuals has the classic form with less than 2% residual BCKD complex activity and exhibits the most serious phenotype. Generally, patients with classic MSUD appear normal at birth but show poor feeding and lethargy within a week followed by more severe symptoms such as convulsions and progressive brain damage.…”