"Clinical profile and subtypes11"
"Newborns with the classic variant appear healthy at birth, but after a symptom-free window of roughly 4–7 days they develop poor feeding, emesis, failure to thrive, and increasing lethargy, heralding metabolic decompensation. During these crises, the heavy isoleucine burden imparts the characteristic burnt-sugar (“maple syrup”) odour to urine, though the scent can be faint in the first days of life 11."
"Elevated BCAAs out-compete other essential amino acids at the blood–brain barrier."
"Excess branched-chain amino acids (BCAAs) impair neurotransmitter synthesis and restrict neuronal growth."
"Elevated BCAAs out-compete other essential amino acids at the blood–brain barrier."
"Accumulated branched-chain ketoacids disrupt the Krebs cycle, provoking cerebral energy failure that manifests as oedema and aberrant myelination."
"It is inherited in an autosomal recessive pattern and various different genes have been implicated 1. Branched-chain α-ketoacid dehydrogenase (BCKD) complex is composed of four enzymatic subunits—E1α, E1β, E2, and E3. Each is encoded by a distinct gene on a separate chromosome: BCKDHA on chromosome 19 produces E1α; BCKDHB on chromosome 6 produces E1β; DBT on chromosome 1 produces E2; and DLD on chromosome 7 produces E3. Although pathogenic variants in these genes strongly influence the clinical picture of maple-syrup-urine disease (MSUD), they do not fully explain its variability 11."
"T1: low signal intensity"
"T2: high signal intensity"
"DWI: the posterior limbs of the internal capsules and optic radiations and the central corticospinal tracts within the cerebral hemispheres exhibit high diffusion signal"
"MR spectroscopy: single-voxel proton MR spectroscopy may show the presence of branched-chain amino acids and branched-chain alpha-keto acids resonating at 0.9-1.0 ppm, especially during a metabolic crisis 1,2"
"Although pathogenic variants in the genes coding for any of the four BCKD subunits (E1α, E1β, E2, E3) can underlie the classic, intermediate, or intermittent phenotypes, residual enzyme activity is higher in the latter two, so their manifestations tend to be milder. The classic form - most often linked to mutations in BCKDHB - is the commonest and produces the most extensive central-nervous-system injury 11."
"Although pathogenic variants in the genes coding for any of the four BCKD subunits (E1α, E1β, E2, E3) can underlie the classic, intermediate, or intermittent phenotypes, residual enzyme activity is higher in the latter two, so their manifestations tend to be milder. The classic form - most often linked to mutations in BCKDHB - is the commonest and produces the most extensive central-nervous-system injury 11."
"It is inherited in an autosomal recessive pattern and various different genes have been implicated 1. Branched-chain α-ketoacid dehydrogenase (BCKD) complex is composed of four enzymatic subunits—E1α, E1β, E2, and E3. Each is encoded by a distinct gene on a separate chromosome: BCKDHA on chromosome 19 produces E1α; BCKDHB on chromosome 6 produces E1β; DBT on chromosome 1 produces E2; and DLD on chromosome 7 produces E3. Although pathogenic variants in these genes strongly influence the clinical picture of maple-syrup-urine disease (MSUD), they do not fully explain its variability 11."
"Excess branched-chain amino acids (BCAAs) impair neurotransmitter synthesis and restrict neuronal growth."
"Elevated BCAAs out-compete other essential amino acids at the blood–brain barrier."
"Accumulated branched-chain ketoacids disrupt the Krebs cycle, provoking cerebral energy failure that manifests as oedema and aberrant myelination."
"It is inherited in an autosomal recessive pattern and various different genes have been implicated 1. Branched-chain α-ketoacid dehydrogenase (BCKD) complex is composed of four enzymatic subunits—E1α, E1β, E2, and E3. Each is encoded by a distinct gene on a separate chromosome: BCKDHA on chromosome 19 produces E1α; BCKDHB on chromosome 6 produces E1β; DBT on chromosome 1 produces E2; and DLD on chromosome 7 produces E3. Although pathogenic variants in these genes strongly influence the clinical picture of maple-syrup-urine disease (MSUD), they do not fully explain its variability 11."
Expected headings
"Serology"
"Signal characteristics"
"Although pathogenic variants in the genes coding for any of the four BCKD subunits (E1α, E1β, E2, E3) can underlie the classic, intermediate, or intermittent phenotypes, residual enzyme activity is higher in the latter two, so their manifestations tend to be milder. The classic form - most often linked to mutations in BCKDHB - is the commonest and produces the most extensive central-nervous-system injury 11."
"predominantly in the cerebellar white matter, cerebral peduncles, dorsal brainstem, posterior limb of the internal capsule, thalami, globi pallidi, and perirolandic cerebral white matter 8"
"It is inherited in an autosomal recessive pattern and various different genes have been implicated 1. Branched-chain α-ketoacid dehydrogenase (BCKD) complex is composed of four enzymatic subunits—E1α, E1β, E2, and E3. Each is encoded by a distinct gene on a separate chromosome: BCKDHA on chromosome 19 produces E1α; BCKDHB on chromosome 6 produces E1β; DBT on chromosome 1 produces E2; and DLD on chromosome 7 produces E3. Although pathogenic variants in these genes strongly influence the clinical picture of maple-syrup-urine disease (MSUD), they do not fully explain its variability 11."
"There is elevated plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine), allo-isoleucine, and alpha-ketoacids."