Assessment of candidate variants causative of inborn metabolic diseases in SUDI cases in South Africa, and a case report

Abstract

Sudden unexpected death in infants (SUDI) is a devastating event, and unfortunately is still a burden in many parts of the world, including in South Africa. Due to the absence of routine testing for inborn metabolic diseases in newborns and in a post-mortem context, little is known about the presence of metabolic diseases in local SUDI cases. The aim of this study was to genotype five candidate variants previously associated with metabolic disorders in a cohort of SUDI cases (n = 169) from Salt River Mortuary, Cape Town. DNA was isolated from blood, and SNaPshot® PCR and Sanger sequencing were used to genotype the following variants: ACADM: c.583G > A, ACADM: c.985A > G, GCDH: c.877G > A/T, GALT: c.404C > G/T and GALT: c.563A > G. Four carriers of GCDH: c.877G > A/T were identified, while one infant was homozygous for the founder mutation GALT: c.404C > G/T; the latter which is causative of galactosaemia and was previously undiagnosed. During the follow-up with the family, it emerged that the affected infant’s identical twin had subsequently demised. The findings in this study highlight possible new candidate variants to assess in South African SUDI cases, and these results directly contribute to the development of a molecular autopsy which is locally relevant. It is evident that until newborn screening becomes routine and accessible in South Africa, molecular autopsies should include testing for inherited metabolic disorders, as it holds potential to save lives.

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Acknowledgements

Surita Meldau, Caitlin Herbert and Lerato Majara for technical assistance as well as Loyiso Vuko for language translation.

Funding

This research was funded by the National Health Laboratory Service Development Trust grant and the University Research Committee, University of Cape Town.

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Correspondence to Laura Jane Heathfield.

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Heathfield, L.J., Bhengu, W., Louw, S. et al. Assessment of candidate variants causative of inborn metabolic diseases in SUDI cases in South Africa, and a case report. Int J Legal Med (2020). https://doi.org/10.1007/s00414-020-02337-6

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Keywords

  • Sudden unexpected death in infants
  • MCAD deficiency
  • Galactosaemia
  • Glutaric aciduria type 1
  • Molecular autopsy