Early Childhood Mortality Research Articles

Pediatric Morbidity Among Black Haitians in Canada: A Longitudinal Cohort Study.

In the U.S., Black children have disproportionately elevated rates of pediatric morbidity compared with White children, but data are lacking for other countries. We studied the extent to which Black Haitians were at risk of pediatric morbidity in Canada. We analyzed a retrospective cohort of 736,498 children born in Quebec between 2008 and 2020. We identified Black Haitians using the mother tongue and birth country of parents. The outcome was mortality or hospitalization for infectious diseases, allergy, cancer, and other morbidity between birth and 12years of age. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for these outcomes, comparing Haitians with non-Haitians in Cox regression models adjusted for patient characteristics. Compared with non-Haitians, Haitians tended to have a greater risk of pediatric mortality, especially before age 2years (HR 1.56, 95% CI 1.00-2.45). However, Haitian children had a lower risk of hospitalization than non-Haitian children (HR 0.61, 95% CI 0.59-0.63). Haitians were less likely to be hospitalized for infectious diseases, allergies, appendicitis, cancers, fractures, dental caries, and ophthalmologic conditions. Hospitalization rates were low throughout childhood, even though Haitian children were more likely to be born preterm, develop severe neonatal morbidity, and have other adverse outcomes at birth. Haitian children have an elevated risk of neonatal morbidity and early childhood mortality, but lower risk of hospitalization compared with non-Haitians in Canada. The reasons for the disparity are unclear, but greater effort is needed to address potential gaps in healthcare among Black children.

IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport

Mutations in the IER3IP1 (Immediate Early Response-3 Interacting Protein 1) gene can give rise to MEDS1 (Microcephaly with Simplified Gyral Pattern, Epilepsy, and Permanent Neonatal Diabetes Syndrome-1), a severe condition leading to early childhood mortality. The small endoplasmic reticulum (ER)-membrane protein IER3IP1 plays a non-essential role in ER-Golgi transport. Here, we employed secretome and cell-surface proteomics to demonstrate that the absence of IER3IP1 results in the mistrafficking of proteins crucial for neuronal development and survival, including FGFR3, UNC5B and SEMA4D. This phenomenon correlates with the distension of ER membranes and increased lysosomal activity. Notably, the trafficking of cargo receptor ERGIC53 and KDEL-receptor 2 are compromised, with the latter leading to the anomalous secretion of ER-localized chaperones. Our investigation extended to in-utero knock-down of Ier3ip1 in mouse embryo brains, revealing a morphological phenotype in newborn neurons. In summary, our findings provide insights into how the loss or mutation of a 10 kDa small ER-membrane protein can cause a fatal syndrome.

Pili Torti: A Clue to Life-threatening Illness – A Rare Case Report

Menkes kinky hair disease (MKHD) is a rare inherent error of copper metabolism presenting during early infancy with multi-system involvement. It is associated with high morbidity and mortality in early childhood. Characteristic hair changes mirror internal metabolic alterations. Here, we report a case of 13-month-old male child who presented with peculiar changes of skin and hair along with convulsion and high-grade fever. Dermatoscopy and hair mount examination showing pili torti with pigmentary dilution pointed toward the diagnosis of MKHD, which was further enforced with blood investigations showing low copper and ceruloplasmin levels. Cutaneous findings play a crucial role in early diagnosis, thereby reducing morbidity with timely treatment.

The experiences and outcomes of Gypsy, Roma, and Traveller pregnant people in pregnancy: A scoping review.

Within Europe, Roma, Gypsy, and Traveller groups have been marginalized and discriminated against by larger society. Persecution and displacement have resulted in high rates of unemployment, reduced access to education, and poorer health, with significantly increased risk of poverty compared with the general population. In pregnancy, there appears to be a gap in the literature surrounding the experiences and outcomes of pregnant people within these ethnic groups. The aim of this study was therefore to scope published research, specifically questioning "What is the experience of Roma Gypsy and Traveller pregnant people who access maternity care?" and "What are the obstetric outcomes within these groups?" This review followed frameworks proposed by Arksey and O'Malley, Levac, and the Joanna Brigg's Institute. The PRISMA extension for Scoping Reviews (PRISMA-ScR) tool was used. The search strategy and specific terms were chosen using the population-concepts-context framework. Titles and abstracts were reviewed independently by two reviewers. Inclusion and exclusion criteria were defined to set clear guidance for reviewers to identify appropriate studies. Five electronic databases were searched (CINAHL, EMBASE, MEDLINE [OVID] Web of Science and SCOPUS). A charting form was developed to record key characteristics systematically and uniformly from the studies. Five themes were identified: systemic issues, antenatal care, complications of pregnancy, birth experience, and postnatal care. Systemic issues included racism, barriers to care, and adapted antenatal care. Antenatal issues included teenage pregnancy, smoking, risk of venous thrombus embolism, dietary issues, risk of communicable diseases, domestic violence, and mental health concerns. Increased risks of congenital abnormalities, growth restriction, premature labor, and perinatal and early childhood mortality were identified. For Roma women, negative birth experiences were reported, whereas the experiences of Traveller women varied. The findings identified in this study serve to create a framework upon which healthcare providers can tailor the way in which pregnant people from a Roma, Gypsy, or Irish Traveller background are cared for. Using such a framework would hopefully begin to reduce the systematic marginalization and discrimination of these minorities.

Antenatal care coverage and early childhood mortality in Zimbabwe: new interpretations from nationally representative household surveys.

Zimbabwe has implemented universal antenatal care (ANC) policies since 1980 that have significantly contributed to improvements in ANC access and early childhood mortality rates. However, Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), two of Zimbabwe's main sources of health data and evidence, often provide seemingly different estimates of ANC coverage and under-five mortality rates. This creates confusion that can result in disparate policies and practices, with potential negative impacts on mother and child health in Zimbabwe. We conducted a comparability analysis of multiple DHS and MICS datasets to enhance the understanding of point estimates, temporal changes, rural-urban differences and reliability of estimates of ANC coverage and neonatal, infant and under-five mortality rates (NMR, IMR and U5MR, separately) from 2009 to 2019 in Zimbabwe. Our two samples z-tests revealed that both DHS and MICS indicated significant increases in ANC coverage and declines in IMR and U5MR but only from 2009 to 2015. NMR neither increased nor declined from 2009 to 2019. Rural-urban differences were significant for ANC coverage (2009-15 only) but not for NMR, IMR and U5MR. We found that there is a need for more precise DHS and MICS estimates of urban ANC coverage and all estimates of NMR, IMR and U5MR, and that shorter recall periods provide more reliable estimates of ANC coverage in Zimbabwe. Our findings represent new interpretations and clearer insights into progress and gaps around ANC coverage and under-five mortality rates that can inform the development, implementation, monitoring and evaluation of policy and practice responses and further research in Zimbabwe.

Breast-feeding Practices among Primipara mothers at Selected Community, Chennai

Introduction: Breast milk is the best and most comprehensive source of nutrients for babies. Poor baby feeding practices are the cause of 60% of infant and early child mortality worldwide. The growth and development of children may be negatively impacted by inappropriate newborn feeding practices, particularly in underdeveloped and developing nations. Hence the present study was undertaken to determine the Breast-feeding Practices among Primipara Mothers at Selected Community, Chennai. Methods: A descriptive correlational design was used. The study was carried out in a community area in Chennai. Using the purposive sampling technique, 100 primipara mothers with infants between the ages of 1-12 months who fulfil the inclusion criteria were selected after obtaining formal agreement from the relevant authorities of the selected community area and ethical clearance from the institutional ethical committee. The data was gathered through interview method using pre-tested instruments such as background variable proforma, obstetrical variable proforma, and proforma to evaluate primipara mothers' breastfeeding practices. Results: The study findings revealed that 73% of the primipara mothers had moderately adequate practice. None of them in the category of needs improvement. There was a significant association between selected obstetrical variables such as mode of delivery and practice on breast feeding in primipara mothers (p<0.05). Those who had normal vaginal delivery had good practice when compared to those who delivered through LSCS.

Can earlier BCG-Japan and OPV vaccination reduce early infant mortality? A cluster-randomised trial in Guinea-Bissau

ObjectiveTo assess the effect of providing BCG and oral polio vaccine (OPV) at an early home visit after delivery.DesignCluster-randomised trial, randomising 92 geographically defined clusters 1:1 to intervention/control arms.SettingBandim Health...

The effect of folic acid intake on congenital anomalies. A systematic review and meta-analysis.

Congenital anomalies pose a significant challenge to global health and result in considerable morbidity and mortality in early childhood. With the decline of other causes of death among children under five, the burden of congenital anomalies is rising, emphasizing the need for improved prenatal care, screening, and nutrition for pregnant women. This systematic review and meta-analysis aim to estimate the pooled effect of folic acid intake on congenital anomalies. To identify relevant research published up until December 30/2023, we conducted electronic searches of PubMed/Medline, PubMed Central, Hinary, Google, African Journals Online, Web of Science, Science Direct, and Google Scholar databases using predefined eligibility criteria. We used Excel to extract data and evaluated the studies using the JBI appraisal checklist. We computed the pooled effect size with 95% confidence intervals for maternal folic acid intake on congenital anomalies using STATA version 17 and the DerSimonian and Laird random effects meta-analysis model. We assessed statistical heterogeneity using Cochran's Q-test, I 2 statistic, and visual examination of the funnel plot. The review included 16 case-control, cohort, and cross-sectional studies. According to the results of this systematic review and meta-analysis, maternal folic acid intake significantly lowers the incidence of congenital anomalies (odds ratio (OR), 0.23; confidence interval (CI), 0.16, 0.32). Among the included studies, both the Cochrane Q-test statistic (χ2 = 118.82, p < 0.001) and I 2 test statistic (I 2 = 87.38%, p < 0.001) revealed statistically significant heterogeneity. Egger's weighted regression (p < 0.001) and funnel plot show evidence of publication bias in this meta-analysis. The results of the recent meta-analysis and systematic review have demonstrated a significant association between maternal folic acid intake and the risk of congenital anomalies. Specifically, children whose mothers received periconceptional folic acid supplementation had a 77% reduced risk of congenital anomalies. To further investigate the correlation between maternal folic acid supplementation and the occurrence of various congenital anomalies, particularly in developing countries, it is recommended that a comprehensive prospective study be conducted. https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42024511508).

For Want of a Cup: The Rise of Tea in England and the Impact of Water Quality on Mortality

Abstract This paper explores the impact of water quality on mortality by exploiting a natural experiment: the rise of tea consumption in eighteenth century England. This resulted in an unintentional increase in consumption of boiled water, thereby reducing mortality rates. The methodology uses two identification strategies tying areas with lower initial water quality to larger declines in mortality rates after tea drinking became widespread and following larger volumes of tea imports. Results are robust to the inclusion of controls for income and access to trade. The hypothesis is further bolstered by suggestive evidence from cause specific deaths and early childhood mortality.

Differential regulation of MYC expression by PKHD1/Pkhd1 in human and mouse kidneys: phenotypic implications for recessive polycystic kidney disease.

Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is a severe, hereditary, hepato-renal fibrocystic disorder that leads to early childhood morbidity and mortality. Typical forms of ARPKD are caused by pathogenic variants in the PKHD1 gene, which encodes the fibrocystin/polyductin (FPC) protein. MYC overexpression has been proposed as a driver of renal cystogenesis, but little is known about MYC expression in recessive PKD. In the current study, we provide the first evidence that MYC is overexpressed in kidneys from ARPKD patients and confirm that MYC is upregulated in cystic kidneys from cpk mutant mice. In contrast, renal MYC expression levels were not altered in several Pkhd1 mutant mice that lack a significant cystic kidney phenotype. We leveraged previous observations that the carboxy-terminus of mouse FPC (FPC-CTD) is proteolytically cleaved through Notch-like processing, translocates to the nucleus, and binds to double stranded DNA, to examine whether the FPC-CTD plays a role in regulating MYC/Myc transcription. Using immunofluorescence, reporter gene assays, and ChIP, we demonstrate that both human and mouse FPC-CTD can localize to the nucleus, bind to the MYC/Myc P1 promoter, and activate MYC/Myc expression. Interestingly, we observed species-specific differences in FPC-CTD intracellular trafficking. Furthermore, our informatic analyses revealed limited sequence identity of FPC-CTD across vertebrate phyla and database queries identified temporal differences in PKHD1/Pkhd1 and CYS1/Cys1 expression patterns in mouse and human kidneys. Given that cystin, the Cys1 gene product, is a negative regulator of Myc transcription, these temporal differences in gene expression could contribute to the relative renoprotection from cystogenesis in Pkhd1-deficient mice. Taken together, our findings provide new mechanistic insights into differential mFPC-CTD and hFPC-CTD regulation of MYC expression in renal epithelial cells, which may illuminate the basis for the phenotypic disparities between human patients with PKHD1 pathogenic variants and Pkhd1-mutant mice.

Maternal psychiatric and somatic illness, and the risk of unintentional injuries in children: variation by type of maternal illness, type of injury and child age

BackgroundMaternal mental illness appears to increase the risk of unintentional childhood injuries, which are a common cause of morbidity and mortality in early childhood. However, little is known about the...

АНАЛІЗ ДИНАМІКИ НАРОДЖЕННЯ ДІТЕЙ З АУТОСОМНИМИ ТРИСОМІЯМИ ПО ХМЕЛЬНИЦЬКІЙ ОБЛАСТІ

In the face of challenging modern demographic conditions, the imperative of preserving human life is becoming increasingly urgent. Environmental pollution, a deteriorating ecological landscape, imbalanced nutrition, unhealthy lifestyles, the accumulation of hereditary defects, and a rising genetic burden collectively exert adverse effects on Ukraine's gene pool. This unfortunate scenario contributes to the increased rate of early child mortality and the birth of children with disabilities [7].&#x0D; The objective of this study was to analyze the trends in child births with Down, Edwards, and Patau syndromes while investigating the influence of maternal age on the incidence of these genetic anomalies in the Khmelnytskyi region from 2017 to 2021.&#x0D; We conducted an analysis of statistical data pertaining to newborns, utilizing information from the Main Statistical Office in the Khmelnytskyi region. This investigation was undertaken in collaboration with the medical and genetic consultation department of the KP "Khmelnytskyi City Perinatal Center." It involved a comprehensive review of outpatient records for patients born with Down, Edwards, and Patau syndromes, aimed at understanding the clinical condition of the infants and the course of pregnancy in their mothers.&#x0D; The analysis revealed that a total of 50,475 babies were born in the region over the course of five years. However, an annual decrease in the birth rate was observed, with an average reduction of 705 children per year. The incidence rate of newborns with Down syndrome, Edwards syndrome, and Patau syndrome ranged from 0.10% to 0.13%. During the research period, 45 children with Down syndrome were born in the Khmelnytskyi region. Cytogenetic analysis indicated that 39 of these children (87 %) had a complete trisomy, 4 had a mosaic form (9 %), and 2 (4 %) had a translocation form. Children with complete trisomy exhibited four or more phenotypic features simultaneously. In the region, 12 children were born with Edwards syndrome, including 9 with complete trisomy and 3 with a mosaic form. No newborns were identified with partial trisomy. Cases included both full-term and premature births, as well as instances of infant mortality. Two children with Patau syndrome were born (1 boy in 2017 and 1 girl in 2019), both with complete trisomy. They were born full-term but with low birth weight and multiple developmental disabilities, with one child surviving for 12 hours and the other for 31 hours.&#x0D; Upon analyzing the age of the parents of the probands, it was discovered that the majority (38 mothers, 64 %) were not within the age risk group for having a child with trisomy. This suggests that women of any age can be at risk of having a child with trisomy. Thus, there is a clear need for medical-genetic counseling and prenatal screening for every pregnant woman during the first trimester of pregnancy.

625 Cystic fibrosis–related infant and early-childhood mortality in a cohort from South India: just the tip of the iceberg!

625 Cystic fibrosis–related infant and early-childhood mortality in a cohort from South India: just the tip of the iceberg!

Pkhd1cyli/cyli mice have altered renal Pkhd1 mRNA processing and hormonally sensitive liver disease.

Autosomal-recessive polycystic kidney disease (ARPKD; MIM #263200) is a severe, hereditary, hepato-renal fibrocystic disorder that causes early childhood morbidity and mortality. Mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene, which encodes the protein fibrocystin/polyductin complex (FPC), cause all typical forms of ARPKD. Several mouse lines carrying diverse, genetically engineered disruptions in the orthologous Pkhd1 gene have been generated, but none expresses the classic ARPKD renal phenotype. In the current study, we characterized a spontaneous mouse Pkhd1 mutation that is transmitted as a recessive trait and causescysticliver (cyli), similar to the hepato-biliary disease in ARPKD, but which is exacerbated by age, sex, and parity. We mapped the mutation to Chromosome 1 and determined that an insertion/deletion mutation causes a frameshift within Pkhd1 exon 48, which is predicted to result in a premature termination codon (UGA). Pkhd1cyli/cyli (cyli) mice exhibit a severe liver pathology but lack renal disease. Further analysis revealed that several alternatively spliced Pkhd1 mRNA, all containing exon 48, were expressed in cyli kidneys, but in lower abundance than in wild-type kidneys, suggesting that these transcripts escaped from nonsense-mediated decay (NMD). We identified an AAAAAT motif in exon 48 upstream of the cyli mutation which could enable ribosomal frameshifting, thus potentially allowing production of sufficient amounts of FPC for renoprotection. This mechanism, expressed in a species-specific fashion, may help explain the disparities in the renal phenotype observed between Pkhd1 mutant mice and patients with PKHD1-related disease. KEY MESSAGES: The Pkhd1cyli/cylimouse expresses cystic liver disease, but no kidney phenotype. Pkhd1 mRNA expression is decreased in cyli liver and kidneys compared to wild-type. Ribosomal frameshifting may be responsible for Pkhd1 mRNA escape from NMD. Pkhd1 mRNA escape from NMD could contribute to the absent kidney phenotype.

Examining the prevalence and determinants of early initiation of breastfeeding: Evidence from the 2017/2018 Benin demographic and health survey.

Early initiation of breastfeeding has been noted as one of the well-known and successful interventions that contributes to the reduction of early childhood mortality and morbidity. The Government of Benin has established multi-sectoral institutions and policies to increase the prevalence of early initiation of breastfeeding. However, there is little information on the prevalence and the determinants of early initiation of breastfeeding in Benin. This study therefore sought to examine the prevalence and determinants of early initiation of breastfeeding among women in Benin. This is a secondary data analysis of the 2017/2018 Benin demographic and health survey. The study included weighted sample of 7,223 women between the ages of 15 and 49. STATA was used for the data analysis. We used a multilevel logistic regression to investigate the factors of early breastfeeding initiation in Benin. To determine the significant relationships, the data were reported as odds ratios (ORs) with 95% confidence intervals (CIs) and p-value 0.05. The prevalence of early initiation of breastfeeding among mothers was 56.0%. Early initiation of breastfeeding was lower among employed women (aOR = 0.80, 95% CI = 0.69-0.94), women who had caesarean section (aOR = 0.21, 95% CI = 0.16-0.28), those exposed to mass media (aOR = 0.85, 95% CI = 0.75-0.96) and women who received assistance at birth from skilled worker (aOR = 0.57, 95% CI = 0.46-0.71). The findings of this study showed that four in ten children miss early initiation of breastfeeding in Benin. The findings, therefore, call for the need for policymakers to shape existing programs and consider new programs and policies to help improve early initiation of breastfeeding practices in Benin. It is, therefore, recommended that information, education and communication programs targeting mothers who are less likely to practice early initiation of breastfeeding be formulated, implemented, and monitored accordingly by the Ministry of Health.

Comparative proteomics reveals Cryptosporidium parvum infection disrupts cellular barriers

Cryptosporidium is a protozoan parasite capable of infecting humans and animals and is a leading cause of diarrheal disease and early childhood mortality. The molecular mechanisms underlying invasive infection and its pathogenesis remain largely unknown. To better understand the molecular mechanism of the interaction between C. parvum and host cells, we profiled the changes of host cells membrane proteins extracted using native membrane protein extraction kit between C. parvum-infected HCT-8 cells and the control group after C. parvum infected 6 h combined with quantitative Tandem Mass Tags (TMT) liquid chromatography-dual mass spectrometry proteomic analysis. Among the 4844 quantifiable proteins identified, the expression levels of 625 were upregulated, and those of 116 were downregulated at 6 h post-infection compared with controls (1.5-fold difference in abundance, p < 0.05). Enrichment analysis of the function, protein domain and Kyoto Encyclopedia of Genes and Genomes pathway of the differentially expressed proteins revealed that the differentially expressed proteins were mainly related to biological functions related to the cytoskeleton and cytoplasmic matrix. We also found that infection with C. parvum may destroy HCT-8 intercellular space adhesion. Six proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. Through systematic analysis of proteomics related to HCT-8 cell membranes infected by C. parvum, we found many host membrane proteins that can serve as potential receptors in C. parvum adhesion or invasion. C. parvum infection destroyed host cell barrier function and caused extensive changes in host cytoskeleton proteins, providing a deeper understanding of the molecules and their functions involved in the host-C. parvum interaction. SignificanceThere is a lack of systematic research on the molecular mechanisms underlying the interaction of C. parvum with host cells. Changes of host cell membrane proteins after C. parvum infection may be used to examine the host cell receptors for parasite adhesion and invasion, and how the parasite interacts with these receptors. It is of great significance that host cells undergo membrane fusion to mediate invasion. Through proteomic studies on the host cell membrane after infection with HCT-8 cells by C. parvum, we observed disruption of the host cell cellular barrier function and widespread alteration of host cytoskeletal proteins caused by C. parvum infection, providing a deeper understanding of the molecules and their functions involved in host-C. parvum interaction.

The non-specific effects of maternal immunization on birth outcomes: The evidence, mechanisms, and the implications.

Preterm birth (PTB) and stillbirth remain two of the most important causes of death, morbidity, and disability in childhood. Despite efforts to reduce PTB and stillbirth worldwide, rates of these adverse outcomes remain persistently elevated, independent of income setting. There is an urgent need for more effective interventions to reduce associated neonatal and early childhood morbidity and mortality. Maternal vaccines are a well-established strategy used for prevention of pathogen-specific disease in mothers and infants through transplacental antibody transfer. Beyond these pathogen-specific benefits, some studies have also identified non-specific effects (NSEs) of maternal vaccination protecting against several adverse birth outcomes, including PTB and stillbirth. This paper will review the evidence supporting the NSEs of maternal vaccination on birth outcomes, describe the possible underlying mechanisms, outline the research gaps, and summarize the significance from a global health perspective.

Household Environment Status and Infant Mortality: A Study of West Bengal

The factors influencing infant mortality have been documented in a number studies. A number of individual, biological and household environmental factors were found to be the significant predictor of infant mortality in any human setting. Most existing studies on early childhood mortality in India were based on census data. Using the data from second and third rounds of District Level Household and Facility Survey of India this paper assessed the pattern and degree of association of infant mortality with household environment status at the district level in West Bengal. The estimates of infant mortality rate for districts of West Bengal were derived based on birth history data. The household environment status for each district was determined based on three selected household environment factors, namely, availability of toilet facility, availability of safe drinking water and existence of pucca house. Key findings showed that the northern and western districts of this state were backward in terms of household environment status and mostly the districts of those regions had higher levels of infant mortality. The association of availability of toilet facility with infant mortality was found to be significant and stronger, compared to that of other two household factors.

Cryptosporidium uses multiple distinct secretory organelles to interact with and modify its host cell

Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively remodels intestinal epithelial cells, building an elaborate interface structure. How this occurs at the molecular level and the contributing parasite factors are largely unknown. Here, we generated a whole-cell spatial proteome of the Cryptosporidium sporozoite and used genetic and cell biological experimentation to discover the Cryptosporidium-secreted effector proteome. These findings reveal multiple organelles, including an original secretory organelle, and generate numerous compartment markers by tagging native gene loci. We show that secreted proteins are delivered to the parasite-host interface, where they assemble into different structures including a ring that anchors the parasite into its unique epicellular niche. Cryptosporidium thus uses a complex set of secretion systems during and following invasion that act in concert to subjugate its host cell.

Pathogenicity Analysis of a Novel Variant in GTPBP3 Causing Mitochondrial Disease and Systematic Literature Review

Defect of GTPBP3, the human mitochondrial tRNA-modifying enzyme, can lead to Combined Oxidative Phosphorylation Deficiency 23 (COXPD23). Up to now, about 20 different variants of the GTPBP3 gene have been reported; however, genotype-phenotype analysis has rarely been described. Here, we reported a 9-year-old boy with COXPD23 who presented with hyperlactatemia, hypertrophic cardiomyopathy, seizures, feeding difficulties, intellectual disability and motor developmental delay, and abnormal visual development. Biallelic pathogenic variants of the GTPBP3 gene were identified in this boy, one novel variant c.1102dupC (p. Arg368Profs*22) inherited from the mother and the other known variant c.689A>C (p. Gln230Pro) inherited from father. We curated 18 COXPD23 patients with GTPBP3 variants to investigate the genotype-phenotype correlation. We found that hyperlactatemia and cardiomyopathy were critical clinical features in COXPD23 and the average onset age was 1.7 years (3 months of age for the homozygote). Clinical classification of COXPD23 for the two types, severe and mild, was well described in this study. We observed arrhythmia and congestive heart failure frequently in the severe type with early childhood mortality, while developmental delay was mainly observed in the mild type. The proportion of homozygous variants (71.4%) significantly differed from that of compound heterozygous variants (18.1%) in the severe type. Compared with the variants in gnomAD, the proportion of LOFVs in GTPBP3 was higher in COXPD23 patients (48.6% versus 8.9%, p < 0.0001 ****), and 31% of them were frameshift variants, showing the LOF mechanism of GTPBP3. Additionally, the variants in patients were significantly enriched in the TrmE-type G domain, indicating that the G domain was crucial for GTPBP3 protein function. The TrmE-type G domain contained several significant motifs involved in the binding of guanine nucleotides and Mg2+, the hydrolysis of GTP, and the regulation of the functional status of GTPases. In conclusion, we reported a mild COXPD23 case with typical GTPBP3-related symptoms, including seizures and abnormal visual development seldom observed previously. Our study provides novel insight into understanding the clinical diagnosis and genetic counseling of patients with COXPD23 by exploring the genetic pathogenesis and genotype-phenotype correlation of COXPD23.