Top

Published in:

01-09-2020 | Autopsy | Short Communication

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

Authors: Laura Jane Heathfield, Wenelisile Bhengu, Susan Louw, Lorna Jean Martin, Raj Ramesar

Published in: International Journal of Legal Medicine | Issue 5/2020

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.

Available only for authorised users

Dronamraju K (1992) Profiles in genetics: Archibald E. Garrod (1857-1936). Am J Hum Genet 51:216–219PubMedPubMedCentral

Mak CM, Lee H-CH, Chan AY-W, Lam C-W (2013) Inborn errors of metabolism and expanded newborn screening: review and update. Crit Rev Clin Lab Sci 50:142–162CrossRef

South African Government (1959) The Inquests Act 58 of 1959

South African Government (2004) The National Health Act No 61 of 2003

Kinney HC, Thach BT (2009) The sudden infant death syndrome. N Engl J Med 361:795–805CrossRef

Bennett MJ, Powell S (1994) Metabolic disease and sudden, unexpected death in infancy. Hum Pathol 25:742–746CrossRef

Opdal SH, Rognum TO (2004) The sudden infant death syndrome gene: does it exist? Pediatrics 114:e506–e512CrossRef

Krous HF, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T, Cutz E, Hanzlick R, Keens TG, Mitchell EA (2004) Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics 114:234–238CrossRef

Matsubara Y, Narisawa K, Miyabayashi S, Tada K, Coates PM, Bachmann C, Elsas LJ II, Pollitt RJ, Rhead WJ, Roe CR (1990) Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency. Biochem Biophys Res Commun 171:498–505CrossRef

10.

Yokota I, Coates PM, Hale DE, Rinaldo P, Tanaka K (1991) Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain Acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency. Am J Hum Genet 49:1280–1291PubMedPubMedCentral

11.

Miller ME, Brooks JG, Forbes N, Insel R (1992) Frequency of medium-chain acyl-CoA dehydrogenase deficiency G-985 mutation in sudden infant death syndrome. Pediatr Res 31:305–307CrossRef

12.

Dundar M, Lanyon WG, Connor JM (1993) Scottish frequency of the common G985 mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene and the role of MCAD deficiency in sudden infant death syndrome (SIDS). J Inherit Metab Dis 16:991–993CrossRef

13.

Lecoq I, Mallet E, Bonté JB et al (1995) Screening of A985 to G mutation of medium-chain acyl-CoA dehydrogenase (MCAD) gene in Normandy. Evaluation of the role of MCAD deficiency in sudden infant death. C R Séances Soc Biol Fil 189:295–301PubMed

14.

Brackett JC, Sims HF, Steiner RD, Nunge M, Zimmerman EM, deMartinville B, Rinaldo P, Slaugh R, Strauss AW (1994) A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden neonatal death. J Clin Invest 94:1477–1483CrossRef

15.

Rhead WJ (2006) Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: a global perspective. J Inherit Metab Dis 29:370–377CrossRef

16.

van der Watt G, Owen EP, Berman P, Meldau S, Watermeyer N, Olpin SE, Manning NJ, Baumgarten I, Leisegang F, Henderson H (2010) Glutaric aciduria type 1 in South Africa-high incidence of glutaryl-CoA dehydrogenase deficiency in black South Africans. Mol Genet Metab 101:178–182CrossRef

17.

Kölker S, Christensen E, Leonard JV, Greenberg CR, Boneh A, Burlina AB, Burlina AP, Dixon M, Duran M, García Cazorla A, Goodman SI, Koeller DM, Kyllerman M, Mühlhausen C, Müller E, Okun JG, Wilcken B, Hoffmann GF, Burgard P (2011) Diagnosis and management of glutaric aciduria type I – revised recommendations. J Inherit Metab Dis 34:677–694CrossRef

18.

Henderson H, Leisegang F, Brown R, Eley B (2002) The clinical and molecular spectrum of galactosemia in patients from the Cape Town region of South Africa. BMC Pediatr 2:7CrossRef

19.

Kalckar HM, Kinoshita JH, Donnell GN (1973) Galactosemia: biochemistry, genetics, pathophysiology, and developmental aspects. In: Biology of brain dysfunction. Springer US, Boston, pp 31–88CrossRef

20.

Garmany TH, Wambach JA, Heins HB et al (2008) Population and disease-based prevalence of the common mutations associated with surfactant deficiency. Pediatr Res 63:645–649CrossRef

21.

Jumbo-Lucioni PP, Garber K, Kiel J, Baric I, Berry GT, Bosch A, Burlina A, Chiesa A, Pico MLC, Estrada SC, Henderson H, Leslie N, Longo N, Morris AAM, Ramirez-Farias C, Scheweitzer-Krantz S, Silao CLT, Vela-Amieva M, Waisbren S, Fridovich-Keil JL (2012) Diversity of approaches to classic galactosemia around the world: a comparison of diagnosis, intervention, and outcomes. J Inherit Metab Dis 35:1037–1049CrossRef

22.

Heathfield LJ, Martin LJ, Ramesar R (2019) A 5-year retrospective analysis of infant death at Salt River Mortuary, Cape Town South African. J Child Health (Accepted)

23.

Heathfield LJ, Maistry S, Martin LJ et al (2017) Ethical considerations in forensic genetics research on tissue samples collected post-mortem in Cape Town, South Africa. BMC Med Ethics 18:1–8CrossRef

24.

Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215CrossRef

25.

ZymoResearch (2011) Quick-DNA™ Miniprep kit instruction manual. Zymo Res Corp, pp 1–11

26.

Vernarecci S, Ottaviani E, Agostino A, Mei E, Calandro L, Montagna P (2015) Quantifiler® trio kit and forensic samples management: a matter of degradation. Forensic Sci Int Genet 16:77–85CrossRef

27.

Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucliec Acids Symp Ser 41:95–98

28.

Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–423CrossRef

29.

Khalid JM, Oerton J, Cortina-Borja M, Andresen BS, Besley G, Dalton RN, Downing M, Green A, Henderson M, Leonard J, Dezateux C, UK Collaborative Study of Newborn Screening for MCADD (2008) Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants. J Med Screen 15:112–117CrossRef

30.

Leal J, Ades AE, Wordsworth S, Dezateux C (2014) Regional differences in the frequency of the c.985A>G ACADM mutation: findings from a meta-regression of genotyping and screening studies. Clin Genet 85:253–259CrossRef

31.

Gregersen N, Winter V, Curtis D et al Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: the prevalent mutation G985 (K304E) is subject to a strong founder effect from northwestern Europe. Hum Hered 43:342–350

32.

Rathi N, Rathi A (2011) Galactosemia presenting as recurrent sepsis. J Trop Pediatr 57:487–489CrossRef

33.

Kelly S (1971) Septicemia in galactosemia. JAMA 216:330CrossRef

34.

Barr PH (1992) Association of Escherichia coli sepsis and galactosemia in neonates. J Am Board Fam Pract 5:89–91PubMed

35.

Shurin SB (1977) Escherichia coli septicemia in neonates with galactosemia. N Engl J Med 297:1403–1404PubMed

36.

Levy HL, Sepe SJ, Shih VE, Vawter GF, Klein JO (1977) Sepsis due to Escherichia coli in neonates with galactosemia. N Engl J Med 297:823–825CrossRef

37.

Verma S, Bharti B, Inusha P (2010) Association of fungal sepsis and galactosemia. Indian J Pediatr 77:695–696CrossRef

38.

Burman LA, Norrby R, Trollfors B (1985) Invasive pneumococcal infections: incidence, predisposing factors, and prognosis. Rev Infect Dis 7:133–142CrossRef

39.

Mathews S, Martin L, Scott C, et al (2015) Every child counts: lessons learned from the south African child death review pilot. A research brief. Cape Town

40.

Mazzanti A, Priori SG (2012) Molecular autopsy for sudden unexplained death? Time to discuss pros and cons. J Cardiovasc Electrophysiol 23:1099–1102CrossRef

41.

Michaud K, Fellmann F, Abriel H et al (2009) Molecular autopsy in sudden cardiac death and its implication for families: discussion of the practical, legal and ethical aspects of the multidisciplinary collaboration. Swiss Med Wkly 139:712–718PubMed

Title: Assessment of candidate variants causative of inborn metabolic diseases in SUDI cases in South Africa, and a case report
Authors: Laura Jane Heathfield
Wenelisile Bhengu
Susan Louw
Lorna Jean Martin
Raj Ramesar
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Autopsy
Sudden Infant Death Syndrome
Galactosemia
Published in: International Journal of Legal Medicine / Issue 5/2020
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-020-02337-6

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2020

A distant relationship?—investigation of correlations between DNA isolated from backspatter traces recovered from firearms, wound profile characteristics, and shooting distance

Letter to the editor: the successful identification of a scuba diver’s corpse after 26 years of submersion

Beyond metrics and morphology: the potential of FTIR-ATR and chemometrics to estimate age-at-death in human bone

Correction to: Intra- and intermuscular variations of postmortem protein degradation for PMI estimation

Skin pigmentation and genetic variants in an admixed Brazilian population of primarily European ancestry

Effects of cocaine and levamisole (as adulterant) on the isolated perfused Langendorff heart