Retrospective analysis on clinical data and genetic variations of patients with beta-ketothiolase deficiency / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
; (6): 199-202, 2019.
Article
ي Zh
| WPRIM
| ID: wpr-775769
المكتبة المسؤولة:
WPRO
ABSTRACT
OBJECTIVE@#To summarize the clinical, biochemical and molecular characteristics of 8 patients with beta-ketothiolase deficiency (BKD).@*METHODS@#Clinical characteristics, biochemical markers detected by tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS), and variations of ACAT1 gene of the 8 patients were reviewed.@*RESULTS@#Three patients were diagnosed by newborn screening and were asymptomatic. Five patients showed dyspnea and metabolic acidosis through high risk screening. Blood methylcrotonyl carnitine (C51) were 0.43 (0.20-0.89) μmol/L and 3-hydroxyisovaleryl carnitine(C5-OH) were 1.37 (0.98-3.40) μmol/L. Both were significantly higher than those of healthy controls (PG (p.N375S) variant, which accounted for 28.6% of all 14 mutant alleles. Four novel variants, namely c.229delG (p.E77KfsTer10), c.373G>T (p.V125F), c.419T>G (p.L140R) and c.72+1G>A, were discovered. Pathogenicity assessment of two highly conservative missense variants (p.V125F) and (p.L140R) were 0.994 and 1.0 (Scores obtained from PolyPhen2), and PROVEAN scores were -4.652 and -5.399, respectively. c.72+1g>a was suspected (by Human Splicing Finder) to alter the wild type donor motif and most probably affect the splicing.@*CONCLUSION@#Clinicians should consider MS/MS and GC/MS testing for those with unexplained neurological symptoms and metabolic acidosis in order to attain early diagnosis of BKD. Genetic testing should be used to confirm the diagnosis.
النص الكامل:
1
الفهرس:
WPRIM
الموضوع الرئيسي:
Acetyl-CoA C-Acyltransferase
/
Carnitine
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Retrospective Studies
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Tandem Mass Spectrometry
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Amino Acid Metabolism, Inborn Errors
نوع الدراسة:
Observational_studies
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Screening_studies
المحددات:
Humans
/
Newborn
اللغة:
Zh
مجلة:
Chinese Journal of Medical Genetics
السنة:
2019
نوع:
Article