Related Experiment Video
Updated: Aug 11, 2026
A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis
A Boneh1, B S Andresen, N Gregersen
1Metabolic Service and Newborn Screening Laboratory, Genetic Health Services Victoria, Melbourne, Australia. avihu.boneh@ghsv.org.au
Insights
Newborn screening identified very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) in six infants. Early blood sample timing and genetic mutation analysis are crucial for accurate VLCADD diagnosis in newborns.
Area of Science:
- Biochemistry
- Genetics
- Newborn Screening
- Metabolic Disorders
Background:
- Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a rare inherited metabolic disorder.
- Newborn screening programs aim to detect treatable conditions early.
- Accurate diagnosis of VLCADD in newborns is critical for timely intervention.
Purpose of the Study:
- To report the prevalence and diagnostic challenges of VLCADD identified through newborn screening in Victoria.
- To evaluate the utility of blood sample timing and mutation analysis for VLCADD diagnosis.
- To highlight the importance of genotype-phenotype correlation for patient management.
Main Methods:
- Retrospective analysis of newborn screening data over three years in Victoria.
- Genetic mutation analysis (identifying known and novel mutations) in affected infants.
- Comparison of diagnostic results from initial blood samples (48-72 h) versus later samples and urine analysis.
Main Results:
- Six cases of VLCADD were diagnosed, yielding a prevalence of 1:31,500.
- Seven known and two novel mutations were identified; 2/6 were homozygotes, 4/6 compound heterozygotes.
- Initial blood samples were diagnostic, but repeat samples at older ages were normal in 4/6 infants; urine analysis was consistently normal.
Conclusions:
- The timing of blood collection for newborn screening is critical for VLCADD detection.
- Mutation analysis is essential to prevent false-negative diagnoses in asymptomatic newborns.
- Genotype-phenotype correlations aid in tailoring follow-up and treatment strategies for VLCADD patients.
Abstract:
We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false-negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients.
