Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease

Liu,Yi‑Dan; Chu,Xu; Liu,Rui‑Hua; Sun,Ying; Kong,Qing‑Xia; Li,Qiu‑Bo

doi:10.3892/mmr.2019.10133

Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease

Authors:
- Yi‑Dan Liu
- Xu Chu
- Rui‑Hua Liu
- Ying Sun
- Qing‑Xia Kong
- Qiu‑Bo Li
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Affiliations: Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China, Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
Published online on: April 5, 2019 https://doi.org/10.3892/mmr.2019.10133
Pages: 4872-4880
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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. 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. An 11‑day‑old boy was admitted to the hospital with paroxysmal spasticity of lower extremities. 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. 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. 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 E1β 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.

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