Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease.
Mol Med Rep
; 19(6): 4872-4880, 2019 Jun.
Article
em En
| MEDLINE
| ID: mdl-30957186
ABSTRACT
Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in genes that encode subunits of the branchedchain αketoacid dehydrogenase (BCKD) complex. Impairment of the BCKD complex results in an abnormal accumulation of branchedchain amino acids and their corresponding branchedchain keto acids in the blood and cerebrospinal fluid, which are neurovirulent and may become lifethreatening. An 11dayold boy was admitted to the hospital with paroxysmal spasticity of lower extremities. Of note, his 10yearold sister presented similar symptoms during the neonatal period, and her condition was diagnosed as MSUD when she was 1.5 years old. 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 ß (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. 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). Neither of the BCKDHB alleles in the compound heterozygote patients is able to generate normal E1ß subunits, resulting in a possible impairment of the activity of the BCKD complex. 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Extremidade Inferior
/
Irmãos
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3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)
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Doença da Urina de Xarope de Bordo
Tipo de estudo:
Diagnostic_studies
Limite:
Child
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article