![]() In the wide array of inherited metabolic disorders, In the present study, it was hypothesized that the two novel heterozygous mutations in the BCKDHB gene found in the Chinese family may be responsible for the phenotype of the two siblings with MSUD. Neither of the BCKDHB alleles in the compound heterozygote patients is able to generate normal E1β subunits, resulting in a possible impairment of the activity of the BCKD complex. The missense mutation c.1076G>A results in an amino acid substitution from arginine to lysine at position 359 (p.Arg359Lys), whereas the mutation c.705delT results in the replacement of a cysteine at position 235 with a stop codon (p.Cys235Ter). Genetic screening was performed, and the boy and his sister exhibited two novel compound heterozygous mutations in the branched chain keto acid dehydrogenase E1 subunit β (BCKDHB) gene: A substitution from guanine to adenine in the coding region at position 1,076 (c.1,076G>A) in exon 10 and a deletion of a thymine at position 705 (c.705delT) in exon 6. Of note, his 10‑year‑old sister presented similar symptoms during the neonatal period, and her condition was diagnosed as MSUD when she was 1.5 years old. An 11‑day‑old boy was admitted to the hospital with paroxysmal spasticity of lower extremities. Impairment of the BCKD complex results in an abnormal accumulation of branched‑chain amino acids and their corresponding branched‑chain keto acids in the blood and cerebrospinal fluid, which are neurovirulent and may become life‑threatening. ![]() Early imaging diagnosis of this condition can prevent the progress of neurological deficits and help in appropriate management of the disease.Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in genes that encode subunits of the branched‑chain α‑ketoacid dehydrogenase (BCKD) complex. MSUD is a rare autosomal recessive disorder of BCAA metabolism. In early infancy, brain oedema which includes brainstem and posterior fossa is highly suggestive of MSUD. ![]() Corticospinal tracts are also commonly involved. In classic MSUD oedema/restriction pattern usually affects the dorsal brainstem, cerebral peduncles, thalami, globi pallidi and cerebellar white matter. The changes in cell osmolarity and metabolism can reverse completely after metabolic correction in metabolic decompensated MSUD with clinical neurological improvement. Acute “metabolic rescue” to reverse cerebral oedema may require haemodialysis during acute crisis to limit neurotoxicity. Metabolic "intoxication" at any age may be provoked by infection, injury, stress, fasting, or even pregnancy. MSUD has potentially favourable outcome with strict dietary control and aggressive treatment of metabolic crises, and may survive to adulthood if well controlled, as in this case report. DWI is more sensitive than conventional MRI in detecting MSUD brain alterations and it can become a useful tool for early diagnosis and follow-up. NECT of brain shows diffuse bilaterally symmetrical oedema not sparing brainstem and cerebellum. Classic appearing MSUD oedema involving cerebellar white matter, brain stem, globus pallidus, thalamus, cerebral peduncles, and corticospinal tracts. Imaging features are diagnostic in the early weeks of life. Maple syrup odour may be difficult to identify in first few days of life. In crisis, patient’s urine smells like maple syrup, secondary to the large accumulation of isoleucine. If untreated, MSUD can lead to seizures, coma, and death. īeginning in early infancy, within the 4-7 days of life this condition presents with poor feeding, vomiting, lethargy and developmental delay. Increased plasma isoleucine is associated with maple syrup odour. The rapid accumulation of leucine in particular causes neurological symptoms. This disease leads to accumulation of BCAA and metabolites. In most patients, onset occurs in the neonatal period and infancy. It is divided into four major categories: Classic, intermediate, intermittent, and thiamine-responsive, which carry differing symptoms and prognostic factors. This disease has a recessive autosomic inheritance, with an incidence of 1/185,000 newborns, without differences between male and female. Background: Maple syrup urine disease (MSUD) is secondary to a deficiency of deshydrogenase complex of a cetoacid of branched-chain.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |