Diagnostic Odyssey of Atypical Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD) Explained by Three Allelic Products From Two Pathogenic Variants.
Yutaka Furuta, Lynette C Rives, T Andrew Burrow et al.
✦ AI-curated · Sources linked
Case in brief
A 22-year-old male presented with an atypically mild form of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). Genetic analysis revealed a pathogenic frameshift variant inherited from the mother and a rare noncoding variant from the father, which was shown to disrupt normal splicing. The presence of residual normal transcripts from the paternal allele likely accounted for the patient's milder symptoms.
What made this case unusual
The case highlights the impact of a noncoding variant on splicing, leading to the production of both normal and aberrant transcripts, which is uncommon in LCHADD presentations.
Diagnostic / clinical pearl
Clinicians should consider the role of noncoding variants in splicing when evaluating atypical presentations of genetic disorders like LCHADD.
Why it matters
Understanding the effects of allelic variants on splicing can aid in the diagnosis and management of patients with atypical phenotypes in metabolic disorders.