Inborn errors of metabolism in a cohort of pregnancies with non-immune hydrops fetalis: a single center experience
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Zandrè Bruwer
Abstract
Objective:
The purpose of this study was to determine the frequency of non-immune hydrops fetalis (NIHF) among all pregnancies referred for prenatal care at Sultan Qaboos University Hospital (SQUH) during the study period and to evaluate the underlying etiologies of NIH.
Study design:
All pregnancies referred to SQUH between February 2014 and December 2015 were identified, and all pregnancies meeting the diagnosis of NIHF were included in this study. All cases of NIHF referred to our center during this period underwent standard systematic diagnostic work-up that included biochemical and molecular studies in addition to the standard investigations for hydrops fetalis. Clinical characteristics and results of the diagnostic work-up were retrospectively reviewed.
Results:
A total of 3234 pregnancies were referred for prenatal care at SQUH during the study period, and 12 pregnancies were affected by NIHF. An underlying diagnosis was established in nine cases, and the majority of cases (7/9) were caused by inborn errors of metabolism (IEM). These included a novel homozygous variant in the AARS2 gene (5/7) and two cases of galactosialidosis (2/7).
Conclusion:
IEM was a major cause of NIHF in this cohort. The AARS2 variant accounts for a significant number of cases with NIHF in this cohort of Omani patients.
Acknowledgments
The authors express gratitude to the families for their involvement in the study and gratefully acknowledge Maria Al-Hinai for her contribution with regard to data collection.
Author’s statement
Conflict of interest: Authors state no conflict of interest.
Material and methods: Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
References
[1] Potter EL. Universal oedema of the fetus unassociated with erythroblastosis. Am J Obstet Gynaecol. 1943;46: 130–34.10.1016/S0002-9378(16)40458-8Search in Google Scholar
[2] Abrams ME, Meredith KS, Kinnard P, Clark RH. Hydrops fetalis: a retrospective review of cases reported to a large national database and identification of risk factors associated with death. Pediatrics. 2007;120:84–9.10.1542/peds.2006-3680Search in Google Scholar
[3] Bellini C, Hennekam RC, Fulcheri E, Rutigliani M, Morcaldi G, Boccardo F, et al. Etiology of nonimmune hydrops fetalis: a systematic review. Am J Med Genet A. 2009;149A:844–51.10.1002/ajmg.a.32655Search in Google Scholar
[4] Bellini C, Hennekam RC. Non-immune hydrops fetalis: a short review of etiology and pathophysiology. Am J Med Genet. 2012;158A:597–605.10.1002/ajmg.a.34438Search in Google Scholar
[5] Huang HR, Tsay PK, Chiang MC, Lien R, Chou YH. Prognostic factors and clinical features in liveborn neonates with hydrops fetalis. Am J Perinatol. 2007;24:33–8.10.1055/s-2006-958158Search in Google Scholar
[6] Heinonen S, Ryynanen M, Kirkinen P. Etiology and outcome of second trimester non-immunologic fetal hydrops. Acta Obstet Gynaecol Scand. 2000;79:15–8.Search in Google Scholar
[7] Machim GA. Hydrops revisited: literature review of 1414 cases published in the 1980s. Am J Med Genet. 1989;34:366–90.10.1002/ajmg.1320340313Search in Google Scholar
[8] Gimovosky AC, Luzi P, Berghella V. Lysosomal storage disease as an etiology of nonimmune hydrops. Am J Obstet Gynaecol. 2015;212:281–90.10.1016/j.ajog.2014.10.007Search in Google Scholar
[9] Bellini C, Donarini G, Paladini D, Calevo MG, Bellini T, Ramenghi LA, et al. Etiology of non-immune hydrops fetalis: an update. Am Med Genet A. 2015;167A:1082–8.10.1002/ajmg.a.36988Search in Google Scholar
[10] Jauniaux E, Van Maldergem L, De Munter C, Moscoso G, Gillerot Y. Nonimmune hydrops fetalis associated with genetic abnormalities. Obstet Gynecol. 1990;75:568–72.Search in Google Scholar
[11] Burin MG, Scholz AP, Gus R, Sanseverino MT, Fritsh A, Magalhães JA, et al. Investigation of lysosomal storage diseases in nonimmune hydrops fetalis. Prenat Diagn. 2004;24:653–7.10.1002/pd.967Search in Google Scholar
[12] Piraud M, Froissart R, Mandon G, Bernard A, Maire I. Amniotic fluid for screening of lysosomal storage diseases presenting in utero (mainly as non-immune hydrops fetalis). Clinica Chimica Acta. 1996;248:143–55.10.1016/0009-8981(95)06250-5Search in Google Scholar
[13] Al-Thihli K, Al Murshedi F, Al-Hashmi N, Al-Mamari W, Islam MM, Al-Yahyaee SA. Consanguinity, endogamy and inborn errors in metabolism in Oman: a cross-sectional study. Hum Hered. 2014;77:183–8.10.1159/000362686Search in Google Scholar
[14] Gort L, Granell MR, Fernandez G, Carreto P, Sanchez A, Coll MJ. Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops fetalis. Prenat Diagn. 2012;32:1139–42.10.1002/pd.3972Search in Google Scholar
[15] Kooper AJ, Janssens PM, de Groot AN, Liebrand-van Sambeek ML, van den Berg CJ, Tan-Sindhunata GB, et al. Lysosomal storage diseases in non-immune hydrops fetalis pregnancies. Clinica Chimica Acta. 2006;371:176–82.10.1016/j.cca.2006.03.007Search in Google Scholar
[16] Whybra C, Mengel E, Russo A, Bahlmann F, Kampmann C, Beck M, et al. Lysosomal storage disorder in non-immunological hydrops fetalis (NIHF) – more common than assumed? Report of four cases with transient NIHF and a review of the literature. Orphanet J Rare Dis. 2012;7:86–95.10.1186/1750-1172-7-86Search in Google Scholar
[17] Gillan JE, Lowden JA, Gaskin K, Cutz E. Congenital ascites as a presenting sign of lysosomal storage disease. J Pediatr. 1984;104:225–31.10.1016/S0022-3476(84)80997-XSearch in Google Scholar
[18] Groener JE, de Graaf FL, Poorthuis BJ, Kanhai HH. Prenatal diagnosis of lysosomal storage diseases using fetal blood. Prenat Diagn. 1999;19:930–3.10.1002/(SICI)1097-0223(199910)19:10<930::AID-PD664>3.0.CO;2-XSearch in Google Scholar
[19] Favre R, Dreux S, Dommergues M, Dumez Y, Luton D, Oury JF, et al. Nonimmune fetal ascites: a series of 79 cases. Am J Obstet Gynecol. 2004;190:407–12.10.1016/j.ajog.2003.09.016Search in Google Scholar
[20] Mahony BS, Filly RA, Callen PW, Chinn DH, Golbus MS. Severe nonimmune hydrops fetalis: sonographic evaluation. Radiology. 1984;151:757–61.10.1148/radiology.151.3.6718738Search in Google Scholar
[21] Fritsch A, Müller AL, Sanseverino MT, Kessler RG, Barrios PM, Patusco LM, et al. Nonimmune hydrops fetalis: two decades of experience in a university hospital. Rev Bras Ginecol Obstet. 2012;34:310–5.10.1590/S0100-72032012000700004Search in Google Scholar
[22] Sohan K, Carroll SG, De La Fuente S, Soothill P, Kyle P. Analysis of outcome in hydrops fetalis in relation to gestational age at diagnosis, cause and treatment. Acta Obstet Gynecol Scand. 2001;80:726–30.10.1034/j.1600-0412.2001.080008726.xSearch in Google Scholar
[23] Takci S, Gharibzadeh M, Yurdakok M, Ozyuncu O, Korkmaz A, Akcoren Z, et al. Etiology and outcome of hydrops fetalis: report of 62 cases. Pediatr Neonatol. 2014;55:108–13.10.1016/j.pedneo.2013.07.008Search in Google Scholar PubMed
[24] Gotz A, Tyynismaa H, Euro L, et al. Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. Am J Hum Genet. 2011;88: 635–42.10.1016/j.ajhg.2011.04.006Search in Google Scholar PubMed PubMed Central
[25] Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. J Am Med Assoc. 2014;312:68–77.10.1001/jama.2014.7184Search in Google Scholar PubMed PubMed Central
[26] Palombo F, Al-Wardy N, Ruscone GA, Oppo M, Kindi MN, Angius A, et al. A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman. J Hum Genet. 2017;62:259–64.10.1038/jhg.2016.120Search in Google Scholar PubMed
[27] Dallabona C, Diodato D, Kevelam SH, Haack TB, Wong L-J, et al. Novel (ovario) leukodystrophy related to AARS2 mutations. Neurology. 2014;82:2063–71.10.1212/WNL.0000000000000497Search in Google Scholar PubMed PubMed Central
[28] Diadato D, Ghezzi D, Tiranti. The mitochondrial aminoacyl tRNA synthetases: genes and syndromes. Int J Cell Biol. 2014;21:244–55.10.1155/2014/787956Search in Google Scholar PubMed PubMed Central
[29] Santo S, Mansour S, Thilaganathan B, Homfray T, Papageorghiou A, Calvert S, et al. Prenatal diagnosis of non-immune hydrops fetalis: what do we tell the parents? Prenat Diagn. 2011;31:186–95.10.1002/pd.2677Search in Google Scholar PubMed
[30] Al-Riyami A, Afifi M, Al-Kharusi H, Morsi M. National health survey. Ministry of Health. Muscat, Oman, 2000.Search in Google Scholar
©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Fetal anomalies – From prenatal diagnosis to therapy
- Corner of Academy
- The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications
- Research articles – Obstetrics
- Assessment of strain and dyssynchrony in normal fetuses using speckle tracking echocardiography – comparison of three different ultrasound probes
- Inborn errors of metabolism in a cohort of pregnancies with non-immune hydrops fetalis: a single center experience
- Cytogenetic analysis in fetuses with late onset abnormal sonographic findings
- Fetal MRI, lower acceptance by women in research vs. clinical setting
- Neurological complications after therapy for fetal-fetal transfusion syndrome: a systematic review of the outcomes at 24 months
- Evaluation of management and surgical outcomes in pregnancies complicated by acute cholecystitis
- Pentaerythrityltetranitrate (PETN) improves utero- and feto-placental Doppler parameters in pregnancies with impaired utero-placental perfusion in mid-gestation – a secondary analysis of the PETN-pilot trial
- Early onset preeclampsia is associated with an elevated mean platelet volume (MPV) and a greater rise in MPV from time of booking compared with pregnant controls: results of the CAPE study
- Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study
- Risk factors and classification of stillbirth in a Middle Eastern population: a retrospective study
- Selective IUGR in dichorionic twins: what can Doppler assessment and growth discordancy say about neonatal outcomes?
- Early fetal megacystis: Is it possible to predict the prognosis in the first trimester?
- Research articles – Fetus
- A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses
- Birth-weight centiles and the risk of serious adverse neonatal outcomes at term
- Short communication
- Maternal and neonatal vitamin D deficiency and transient tachypnea of the newborn in full term neonates
- Acknowledgment
Articles in the same Issue
- Frontmatter
- Editorial
- Fetal anomalies – From prenatal diagnosis to therapy
- Corner of Academy
- The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications
- Research articles – Obstetrics
- Assessment of strain and dyssynchrony in normal fetuses using speckle tracking echocardiography – comparison of three different ultrasound probes
- Inborn errors of metabolism in a cohort of pregnancies with non-immune hydrops fetalis: a single center experience
- Cytogenetic analysis in fetuses with late onset abnormal sonographic findings
- Fetal MRI, lower acceptance by women in research vs. clinical setting
- Neurological complications after therapy for fetal-fetal transfusion syndrome: a systematic review of the outcomes at 24 months
- Evaluation of management and surgical outcomes in pregnancies complicated by acute cholecystitis
- Pentaerythrityltetranitrate (PETN) improves utero- and feto-placental Doppler parameters in pregnancies with impaired utero-placental perfusion in mid-gestation – a secondary analysis of the PETN-pilot trial
- Early onset preeclampsia is associated with an elevated mean platelet volume (MPV) and a greater rise in MPV from time of booking compared with pregnant controls: results of the CAPE study
- Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study
- Risk factors and classification of stillbirth in a Middle Eastern population: a retrospective study
- Selective IUGR in dichorionic twins: what can Doppler assessment and growth discordancy say about neonatal outcomes?
- Early fetal megacystis: Is it possible to predict the prognosis in the first trimester?
- Research articles – Fetus
- A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses
- Birth-weight centiles and the risk of serious adverse neonatal outcomes at term
- Short communication
- Maternal and neonatal vitamin D deficiency and transient tachypnea of the newborn in full term neonates
- Acknowledgment
