OBJECTIVE: To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature. METHODS: A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038). RESULTS: The proband, a female infant, was delivered by Cesarean section at 36⁺¹ weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms. CONCLUSION O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans ; Female ; Infant, Newborn ; Male ; Mutation ; Hearing Loss, Sensorineural/genetics* ; Diarrhea, Infantile/genetics* ; Exome Sequencing ; Phenotype ; Fetal Growth Retardation ; Hair Diseases ; Facies

OBJECTIVE: To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR). METHODS: A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University on December 6,2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using "hypoparathyroidism""sensorineural deafness""renal dysplasia""HDR""Barakat" and"GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. RESULTS: A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously. CONCLUSION For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.
Humans ; Hypoparathyroidism/diagnosis* ; Female ; Infant, Newborn ; Hearing Loss, Sensorineural/diagnosis* ; GATA3 Transcription Factor/genetics* ; Nephrosis/genetics* ; Phenotype ; Exome Sequencing

Objective:To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR).Methods:A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University in on December 6, 2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using " hypoparathyroidism" " sensorineural deafness" " renal dysplasia" " HDR" " Barakat" and" GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. Results:A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously.Conclusion:For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.

Objective:To explore the value of the neutrophil-to-lymphocyte ratio（NLR）in early prediction of retinopathy of prematurity（ROP）.Methods:The medical records of 325 preterm infants with a gestational age <32 weeks who were admitted to the Neonatology Department of the First Affiliated Hospital of Zhengzhou University from January 1,2019 to December 31,2019 were retrospectively reviewed.The complete blood cell results at 7-10 days of age were collected，including white blood cell，neutrophil，lymphocyte，monocyte，and platelet counts.The NLR，lymphocyte-to-monocyte ratio（LMR），and platelet-to-lymphocyte ratio（PLR）were calculated.Logistic regression analysis was used to assess the risk factors associated with ROP.The receiver operating characteristic curve was performed to evaluate the value of NLR in the early prediction of ROP.Results:A total of 325 infants were involved,including 110（33.8%）with ROP and 215（61.2%）without ROP.The gestational age，birth weight，platelet count，lymphocyte count，and LMR were significantly lower in the ROP group（ P<0.05），whereas the neutrophil count and NLR were found to be significantly higher（ P<0.05）.Multivariate Logistic regression analysis revealed that small gestational age，low birth weight,and high NLR were major risk factors for the development of ROP.The sensitivity and specificity of NLR in early predicting ROP were 90.1% and 74.4%，respectively. Conclusion:The NLR at the first week after birth can serve as a simple method for early prediction of the development of ROP.

Objective:To summarize the clinical characteristics and treatment outcomes of neonatal congenital chylothorax (CC) and to provide evidence for improving its clinical management.Methods:The clinical data from 21 neonates diagnosed with CC and admitted to the Department of Neonatology, the First Affiliated Hospital of Zhengzhou University, from February 2014 to June 2024 were retrospectively reviewed. According to gestational age, patients were classified into preterm group (<37 weeks) and full-term group (≥37 weeks). The clinical manifestations, therapeutic approaches, and outcomes were analyzed.Results:A total of 21 children with CC were included, including 16 males and five females, with an average gestational age of (36.35±2.39) weeks.Pleural effusion was bilateral in 13 cases, right-sided in seven cases, and left-sided in one case. Seven infants presented with fetal hydrops, and nine experienced birth asphyxia. The premature infants were 13 cases and the full-term infants were eight cases.The preterm group had a significantly higher rate of intrauterine therapy and lower serum albumin levels compared with the full-term group ( P<0.05). No significant differences were observed between the two groups in the use of mechanical ventilation, treatment modality, duration of pleural effusion, or length of hospital stay ( P>0.05). Of the 21 cases of CC,12 cases achieved resolution of pleural effusion after conservative treatment, which included thoracentesis, sequential nutritional therapy, and octreotide administration. Eight infants required additional chemical pleurodesis with intrathoracic erythromycin and subsequently recovered. Among all patients, 18 cases were discharged after improvement, and no recurrence was found after telephone follow-up for 8~12 months after birth.Three infants were diagnosed with Down syndrome,one died after early withdrawal of treatment, and the other two with pleural effusion disappeared after treatment were lost to follow-up after discharge. Conclusions:Preterm infants with CC are more likely to receive intrauterine therapy and have lower serum albumin levels than full-term infants. For patients who do not respond to conservative management, chemical pleurodesis with intrathoracic erythromycin can be considered. Most neonates with CC have a favorable prognosis after appropriate treatment.

Objective:To explore the value of the neutrophil-to-lymphocyte ratio（NLR）in early prediction of retinopathy of prematurity（ROP）.Methods:The medical records of 325 preterm infants with a gestational age <32 weeks who were admitted to the Neonatology Department of the First Affiliated Hospital of Zhengzhou University from January 1,2019 to December 31,2019 were retrospectively reviewed.The complete blood cell results at 7-10 days of age were collected，including white blood cell，neutrophil，lymphocyte，monocyte，and platelet counts.The NLR，lymphocyte-to-monocyte ratio（LMR），and platelet-to-lymphocyte ratio（PLR）were calculated.Logistic regression analysis was used to assess the risk factors associated with ROP.The receiver operating characteristic curve was performed to evaluate the value of NLR in the early prediction of ROP.Results:A total of 325 infants were involved,including 110（33.8%）with ROP and 215（61.2%）without ROP.The gestational age，birth weight，platelet count，lymphocyte count，and LMR were significantly lower in the ROP group（ P<0.05），whereas the neutrophil count and NLR were found to be significantly higher（ P<0.05）.Multivariate Logistic regression analysis revealed that small gestational age，low birth weight,and high NLR were major risk factors for the development of ROP.The sensitivity and specificity of NLR in early predicting ROP were 90.1% and 74.4%，respectively. Conclusion:The NLR at the first week after birth can serve as a simple method for early prediction of the development of ROP.

Objective:To summarize the clinical characteristics and treatment outcomes of neonatal congenital chylothorax (CC) and to provide evidence for improving its clinical management.Methods:The clinical data from 21 neonates diagnosed with CC and admitted to the Department of Neonatology, the First Affiliated Hospital of Zhengzhou University, from February 2014 to June 2024 were retrospectively reviewed. According to gestational age, patients were classified into preterm group (<37 weeks) and full-term group (≥37 weeks). The clinical manifestations, therapeutic approaches, and outcomes were analyzed.Results:A total of 21 children with CC were included, including 16 males and five females, with an average gestational age of (36.35±2.39) weeks.Pleural effusion was bilateral in 13 cases, right-sided in seven cases, and left-sided in one case. Seven infants presented with fetal hydrops, and nine experienced birth asphyxia. The premature infants were 13 cases and the full-term infants were eight cases.The preterm group had a significantly higher rate of intrauterine therapy and lower serum albumin levels compared with the full-term group ( P<0.05). No significant differences were observed between the two groups in the use of mechanical ventilation, treatment modality, duration of pleural effusion, or length of hospital stay ( P>0.05). Of the 21 cases of CC,12 cases achieved resolution of pleural effusion after conservative treatment, which included thoracentesis, sequential nutritional therapy, and octreotide administration. Eight infants required additional chemical pleurodesis with intrathoracic erythromycin and subsequently recovered. Among all patients, 18 cases were discharged after improvement, and no recurrence was found after telephone follow-up for 8~12 months after birth.Three infants were diagnosed with Down syndrome,one died after early withdrawal of treatment, and the other two with pleural effusion disappeared after treatment were lost to follow-up after discharge. Conclusions:Preterm infants with CC are more likely to receive intrauterine therapy and have lower serum albumin levels than full-term infants. For patients who do not respond to conservative management, chemical pleurodesis with intrathoracic erythromycin can be considered. Most neonates with CC have a favorable prognosis after appropriate treatment.

Objective:To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR).Methods:A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University in on December 6, 2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using " hypoparathyroidism" " sensorineural deafness" " renal dysplasia" " HDR" " Barakat" and" GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. Results:A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously.Conclusion:For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.

Objective:To construct a Chinese neonatal model of early-onset sepsis (EOS) using the Kaiser Permanente sepsis risk calculator and laboratory indicators and validate its clinical prediction potential.Methods:Newborns with a gestational age of ≥34 weeks, who were hospitalized in the Department of Neonatology, the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2022 were retrospectively recruited.Their clinical data were collected.Predictors were screened via the multivariate regression analysis, and the Nomogram model was constructed using R software and RStudio software.Hosmer-Lemeshow test, receiver operating characteristic curve, the decision curve analysis (DCA) were used to evaluate the prediction potential of the Nomogram.Results:A total of 769 patients were enrolled, including 107 patients in the EOS group (5 culture-confirmed cases and 102 clinically diagnosed cases), and 662 cases in the non-EOS group.Ten variables were screened and introduced into the Nomogram, including the gestational age, birth weight, body temperature, white blood cell count, C-reactive protein, procalcitonin, premature rupture of membranes≥18 h, infection of Group B Streptococcus, ventilator application, and prenatal antibiotics.The predictive model showed good discrimination and consistency, with the area under the curve of 0.834 (95% CI: 0.771-0.896). The DCA of the prediction model showed that it was effective in clinical application within the effective threshold of 6%-95%, with a net benefit following the application of corresponding treatment measures. Conclusions:A Chinese neonatal model of EOS was created by using the Kaiser Permanente sepsis risk calculator and laboratory indicators, which has been validated effective.It provides references for clinical management and the guidance for the use of antibiotics.

A 10-day-old male infant presented with skin erythema and blisters for 6 days. Skin examination showed scattered or confluent erythema all over the body, tense blisters of varying sizes on the normal skin or an erythematous base, and some blisters were ulcerated and erosive; bloody bullae and erythematous erosive patches could be seen on the oral mucosa. Histopathological examination revealed subepidermal blisters, and there were some neutrophils and a few eosinophils in the blisters. Direct immunofluorescence assay showed homogeneous linear IgA and granular C3 deposits along the basement membrane zone, without IgG deposits. The diagnosis of neonatal linear IgA bullous dermatosis was confirmed. After comprehensive treatments including nutritional support and anti-infection treatment, skin erythema and blisters subsided, and the mucosal damage was attenuated. The telephone follow-up 16 months after discharge showed that the infant was in good general condition with normal growth and development, and the oral mucosal lesions had subsided and healed, without new skin lesions.