Gaucher Disease Coexisting with Cytomegalovirus Infection: A Rare Presentation in an Infant.

BACKGROUND Gaucher disease is a rare autosomal recessive disorder characterized by mutations in the glucocerebrosidase gene, resulting in deficient enzyme activity and accumulation of glucocerebroside in macrophages, which leads to pathological changes in affected organs. The atypical clinical manifestations of Gaucher disease often contribute to delays in diagnosis and treatment. CASE REPORT We present the case of a 4-month-old female infant admitted to the Department of Pediatrics with progressive hepatosplenomegaly since birth. Concurrently, she had cytomegalovirus infection and sensory neurological hearing loss. Gaucher disease diagnosis was confirmed through whole-exome sequencing and validated by a glucocerebrosidase activity test, revealing the mutation site as c.1448T>C. This report outlines the differential diagnosis process for Gaucher disease in this infant before confirmation, contributing valuable insights for early diagnosis. CONCLUSIONS Our case underscores the challenge of diagnosing Gaucher disease due to its atypical presentation. The coexistence of cytomegalovirus infection complicates the clinical picture, emphasizing the need for careful differential diagnosis. Unfortunately, delayed diagnosis is all too common in rare diseases like Gaucher disease, even when the clinical presentation is seemingly typical. This highlights the need for increased awareness and education within the medical community to facilitate early recognition, which is essential for prompt intervention and improved outcomes. This report contributes valuable clinical and genetic information, aiming to enhance awareness and deepen the understanding of Gaucher disease in infants, particularly those with concurrent infections.

Social visual preference mediates the effect of cortical thickness on symptom severity in children with autism spectrum disorder.

Background: Evidence suggests that there is a robust relationship between altered neuroanatomy and autistic symptoms in individuals with autism spectrum disorder (ASD). Social visual preference, which is regulated by specific brain regions, is also related to symptom severity. However, there were a few studies explored the potential relationships among brain structure, symptom severity, and social visual preference. Methods: The current study investigated relationships among brain structure, social visual preference, and symptom severity in 43 children with ASD and 26 typically developing (TD) children (aged 2-6 years). Results: Significant differences were found in social visual preference and cortical morphometry between the two groups. Decreased percentage of fixation time in digital social images (%DSI) was negatively related to not only the thickness of the left fusiform gyrus (FG) and right insula, but also the Calibrated Severity Scores for the Autism Diagnostic Observation Schedule-Social Affect (ADOS-SA-CSS). Mediation analysis showed that %DSI partially mediated the relationship between neuroanatomical alterations (specifically, thickness of the left FG and right insula) and symptom severity. Conclusion: These findings offer initial evidence that atypical neuroanatomical alterations may not only result in direct effects on symptom severity but also lead to indirect effects on symptom severity through social visual preference. This finding enhances our understanding of the multiple neural mechanisms implicated in ASD.

Lactobacillus rhamnosus GG and butyrate supplementation in rats with bone cancer reduces mechanical allodynia and increases expression of µ-opioid receptor in the spinal cord.

Introduction: Chronic cancer pain is one of the most unbearable symptoms for the patients with advanced cancer. The treatment of cancer pain continues to possess a major challenge. Here, we report that adjusting gut microbiota via probiotics can reduce bone cancer pain (BCP) in rats. Methods: The model of BCP was produced by tumor cell implantation (TCI) to the tibia in rats. Continuous feeding of Lactobacillus rhamnosus GG (LGG) was used to modulate the gut microbiota. Mechanical allodynia, bone destruction, fecal microbiota, and neurochemical changes in the primary dorsal root ganglion (DRG) and the spinal dorsal horn (DH) were assessed. Results: LGG supplementation (109 CFU/rat/day) delayed the production of BCP for 3-4 days and significantly alleviated mechanical allodynia within the first 2 weeks after TCI. TCI-induced proinflammatory cytokines TNF-α and IL-ß in the DH, and TCI-induced bone destruction in the tibia were both significantly reduced following LGG supplementation examined on day 8 after TCI. Meanwhile, we found that LGG supplementation, in addition to inhibiting TCI-induced pain, resulted in a significantly increased expression of the µ-opioid receptor (MOR) in the DH, but not in the DRG. LGG supplementation significantly potentiated the analgesic effect of morphine. Furthermore, LGG supplementation led to an increase in butyrate levels in the feces and serum and a decrease in histone deacetylase 2 (HDAC2) expression in the DH. Feeding TCI-rats with sodium butyrate solution alone, at a dose of 100 mg/kg, resulted in decreased pain, as well as decreased HDAC2 expression and increased MOR expression in the DH. The increased expression of MOR and decreased HDAC2 were also observed in neuro-2a cells when we treated the cells with serum from TCI rats with supplementation of LGG or sodium butyrate. Discussion: This study provides evidence that reshaping the gut microbiota with probiotics LGG can delay the onset of cancer pain. The butyrate-HDAC2-MOR pathway may be the underlying mechanism for the analgesic effect of LGG. These findings shed light on an effective, safe, and non-invasive approach for cancer pain control and support the clinical implication of probiotics supplementation for patients with BCP.

Genome-wide copy number variation-, validation- and screening study implicates a new copy number polymorphism associated with suicide attempts in major depressive disorder.

BACKGROUND: The genetic basis of suicide attempts (SA) remains unclear. Especially the role of copy number variations (CNVs) remains to be elucidated. The present study aimed to identify susceptibility variants associated with SA among Chinese with major depressive disorder (MDD), covering both CNVs and single-nucleotide polymorphisms (SNPs). METHODS: We conducted a genome-wide association study (GWAS) on MDD patients with and without SA and top results were tested in a replication study. A genome-wide CNV study was also performed. Subsequently, a validation assay using qRT-PCR technology was performed to confirm any associated CNVs and then applied to the entire cohort to examine the association. RESULTS: Although GWAS did not identify any SNPs reaching genome-wide significance, we identified TPH2 as the top susceptibility gene (p-value = 2.75e-05) in gene-based analysis, which is a strong biological candidate for its role in the serotonergic system. As for CNV analysis, we found that the global rate of CNV was higher in SA than that in non-SA subjects (p-value = 0.023). Genome-wide CNV study revealed an SA-associated CNV region that achieved genome-wide significance (corrected p-value = 0.014). The associated CNV was successfully validated with a more rigorous qRT-PCR assay and identified to be a common variant in this cohort. Its deletion rate was higher in SA subjects [OR = 2.05 (1.02-4.12), adjusted p-value = 0.045]. Based on the GTEx database, genetic variants that probed this CNV were significantly associated with the expression level of ZNF33B in two brain regions (p-value < 4.2e-05). In stratified analysis, the CNV showed a significant effect [OR = 2.58 (1.06-6.27), p-value = 0.039] in those with high neuroticism but not in those with average or low neuroticism. CONCLUSIONS: We identified a new common CNV likely involved in the etiology of SA. This finding sheds light on an important role of common CNVs in the pathophysiology of SA, suggesting a new promising avenue for investigating its genetic architecture.

[Value of serum miR-17-92 cluster in diagnosis of retinoblastoma].

OBJECTIVE: To investigate the value of serum miR-17-92 cluster in the diagnosis of retinoblastoma (RB). METHODS: Serum samples were collected from 20 children with RB and 20 healthy controls. Quantitative real-time PCR was used to measure the expression of miR-17-92 cluster. The expression of miR-17-92 cluster was compared between children with different stages of RB and the changes in the expression of miR-17-92 cluster after multimodality therapy were analyzed. The receiver operating characteristic (ROC) curve was used to investigate the value of serum miR-17-92 cluster in the diagnosis of RB. RESULTS: Compared with the healthy controls, the children with RB had significantly higher relative expression of miR-17-3P, miR-17-5P, miR-18a, and miR-20a in serum (P<0.05), and miR-18a showed the greatest increase. There were no significant differences in the relative expression of miR-19a, miR-19b-1, and miR-92a-1 between children with RB and healthy controls (P>0.05). There were no significant differences in the expression of miR-17-5P, miR-17-3P, miR-18a, and miR-20a between the children with early-to-moderate stage of RB and those with advanced stage of RB (P>0.05), but there were significant reductions after multimodality therapy (P<0.05). In the diagnosis of RB, the areas under the ROC curve (AUCs) for serum miR-17-3P, miR-17-5P, miR-18a, and miR-20a were 0.770, 0.755, 0.828, and 0.665 respectively, and miR-18a had the largest AUC, with a sensitivity of 90% and a specificity of 65%. CONCLUSIONS: miR-17-3P, miR-17-5P, miR-18a, and miR-20a are highly expressed in the serum of children with RB, and miR-18a may be used as a new marker for the diagnosis of RB.

[A preliminary study of retinoblastoma-related serum tumor markers].

OBJECTIVE: To screen out retinoblastoma (RB)-related serum tumor markers by measuring the levels of serum alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) in children with RB. METHODS: The levels of seven serum tumor markers (AFP, CEA, NSE, CA125, CA153, CA199, and CA724) were determined in 20 children with RB and 20 healthy children (control) using a chemiluminescent immunoassay. RESULTS: The serum levels and positive rates of NSE, CA153, and CA199 in the RB group were significantly higher than those in the control group (P<0.05). However, there were no significant differences in the levels of AFP, CEA, CA125, and CA724 between the two groups (P>0.05). NSE had the highest sensitivity, but a relatively low specificity for the diagnosis of RB. CA153 and CA199 had a relatively high specificity, but a relatively low sensitivity for the diagnosis of RB. CONCLUSIONS: The serum levels and positive rates of NSE, CA153, and CA199 are high in children with RB. Combined measurement of these three serum tumor markers may have an important diagnostic value for RB.

[Changing trends and clinical characteristics of febrile seizures in children].

OBJECTIVE: To investigate the clinical characteristics and changing trends of febrile seizures (FS) in children. METHODS: The clinical data of 1 922 children with FS admitted from 2004 to 2013 were analyzed retrospectively. The clinical characteristics and changing trends of FS in the two five-year periods were analyzed. RESULTS: In 1 922 children with FS, the male/female ratio was 2.27:1. The mean age at onset was 3.0±1.8 years, while the peak age at onset was 1-3 years. There were 1 556 children (80.96%) with simple FS and 366 (19.04%) with complex FS. The number of children with FS in the second five-year period (1 202 cases) increased by 66.9% compared with that in the first five-year period (720 cases). The proportion of children with complex FS was significantly higher in the second five-year period than in the first five-year period (21.13% vs 15.56%; P<0.05). In children with simple FS, there were no significant differences in the age and body temperature at onset, convulsion duration, and the incidence of complications between the two five-year periods (P>0.05). However, children with complex FS had a significantly lower age at onset, a significantly lower body temperature at onset, a significantly longer convulsion duration, and a significantly higher incidence of complications including myocardial injury and hyponatremia in the second five-year period than in the first five-year period (P<0.05). CONCLUSIONS: In the last decade, the number of children with FS and incidence of complex FS increased, and the outcome became worse according to clinical characteristics, suggesting that more attention should be paid to timely diagnosis and treatment of complex FS.

[Preventive effect of behavioral therapy plus flunarizine in children with migraine].

OBJECTIVE: To investigate the preventive effect of behavioral therapy plus flunarizine in children with migraine. METHODS: Ninety pediatric patients with migraine between January 2011and January 2014 were randomly divided into treatment group (45 cases) and control group (45 cases). The treatment group received behavioral therapy in addition to oral flunarizine, while the control group received oral flunarizine alone. All patients were followed up for 3 months to evaluate the therapeutic effect by the Pediatric Migraine Disability Assessment Score (PedMIDAS) and improved Bussone headache index. RESULTS: There were no significant differences in PedMIDAS (P>0.05) and improved Bussone headache index (P>0.05) between the control and treatment groups before treatment. Significant differences were observed in PedMIDAS (16±8 vs 20±10; P<0.05) and improved Bussone headache index (25±18 vs 37±21; P<0.05) between the two groups after 3 months of treatment. CONCLUSIONS: Preventive treatment of behavioral therapy plus oral flunarizine shows a better clinical efficacy than oral flunarizine alone in children with migraine and holds promise for clinical application.

[Clinical features and risk factors of co-morbid tic disorder in children with attention deficit hyperactivity disorder].

OBJECTIVE: To study the clinical features and risk factors of co-morbid tic disorder (TD) in children with attention deficit hyperactivity disorder (ADHD). METHODS: A total of 312 children with ADHD were involved in this study. Subtypes of co-morbid TD, incidences of TD in different subtypes of ADHD (ADHD-I, ADHD-HI and ADHD-C) were observed. Thirteen potential factors influencing the comorbidity rate of TD in ADHD were evaluated by univariate analysis and multiple logistic regression analysis. RESULTS: Forty-two of 312 children with ADHD suffered from co-morbid TD (13.5%). Comorbidity rate of TD in children with ADHD-C (24.1%) was significantly higher than in those with ADHD-HI (10.9%) and ADHD-I (8.8%) (P<0.05). There were 21 cases (50.0%) of transient TD, 12 cases (28.6%) of chronic TD, and 9 cases (21.4%) of Tourette syndrome. The univariate analysis revealed 6 factors associated with comorbidity: addiction to mobile phone or computer games, poor eating habits, infection, improper family education, poor relationship between parents and poor relationship with schoolmates. Multiple logistic analysis revealed two independent risk factors for comorbidity: improper family education (OR=7.000, P<0.05) and infection (OR=2.564, P<0.05). CONCLUSIONS: The incidence of co-morbid TD in children with ADHD is influenced by many factors, and early interventions should be performed based on the main risk factors.

[Therapeutic effects of exercise-based treatment programme on children with attention-deficit/hyperactivity disorder].

OBJECTIVE: To evaluate the effects of an exercise-based treatment programme (dyslexia, dyspraxia and attention-deficit treatment, DDAT) on various subtypes of attention-deficit/hyperactivity disorder (ADHD). METHOD: Ninety-one ADHD children with standing balance dysfunction (ADHD-I 43, ADHD-HI 15 and ADHD-C 33) were given DDAT for 6 months, the efficacy of DDAT was evaluated before DDAT, three, six months after the treatment and three month after end of the treatment according to SNAP-IV, before and after the treatment by balancing function test and Conners Parents Rating Scale. RESULT: Inattention subscale scores of ADHD-I, ADHD-HI and ADHD-C before and after the interventions were 1.99 ± 0.34, 0.96 ± 0.31, 2.17 ± 0.31and 1.19 ± 0.45, 0.81 ± 0.28, 1.32 ± 0.37, differences of ADHD-I and ADHD-C were significant (P < 0.05), hyperactivity subscale scores of three subtypes of ADHD were 0.81 ± 0.35, 2.01 ± 0.35, 1.96 ± 0.33 vs.0.45 ± 0.33, 0.79 ± 0.41, 1.10 ± 0.35, there were significant differences as well (P < 0.05). The score of hyperactivity symptom was reduced more compared to that of inattention symptom by the SNAP-IV scale parent forms. There were significant difference before and after the treatment based on Conners parent scale for conduct problem (1.11 ± 0.48 vs. 0.76 ± 0.44) , learning problem (1.97 ± 0.58 vs.1.60 ± 0.67), psychosomatic problems (0.61 ± 0.49 vs. 0.29 ± 0.35) , activity/ hyperactivity (1.46 ± 0.69 vs.1.09 ± 0.55) and anxiousness (1.05 ± 0.63 vs.0.62 ± 0.47) as well (P < 0.05); the standing balance dysfunction improved for most of the children, total effective rate was 87.9%, no significant difference was found among the three subtypes (P > 0.05). CONCLUSION: DDAT is a safe and efficient intervention for the ADHD children with standing balance dysfunction, the improvement on hyperactivity symptom was better than that on inattention symptom. This study shows that an exercise-based treatment programme for cerebellum function improves symptoms of ADHD and balance function.

[An epidemiological survey of attention deficit hyperactivity disorder in school-age children in Shenzhen].

OBJECTIVE: To investigate the prevalence of attention deficit hyperactivity disorder (ADHD) and behavior problems among school-age children in Shenzhen City of Guangdong. METHODS: A total of 10553 students in Grades 1-6 from different primary schools in Shenzhen City were assessed by Conners Parent Symptom Questionnaire (PSQ) and Conners Teacher Rating Scale (TRS). Children showing abnormalities according to PSQ or TRS were further assessed according to the diagnostic standard for ADHD as laid out in the diagnostic and statistical manual for mental disorders- 4th edition (DSM-Ⅳ). RESULTS: A total of 8193 PSQ and TRS assessments were completed. The children were aged from 7 to 13 years. The total prevalence rate was 7.60% by PSQ and 5.59 % by TRS. Four hundred and forty-two children were diagnosed having ADHD by DSM-Ⅳ, with a prevalence rate of 5.39%. There were significant differences in the prevalence rate of ADHD among children aged 7 to 13 years (χ2=21.613, P<0.05). In children aged 7 to 9 years, the prevalence rate was higher (above 6%). The prevalence rate of ADHD in boys was significantly higher than in girls (6.65% vs 3.12%; P<0.05). Impulsion and hyperactivity (79.6%), learning (60.6%) and conduct disorders (52.0%) were the main behavioral problems in children with ADHD. The prevalence of learning disorders was higher in girls than in boys. Conclusions The prevalence rate of ADHD in children from primary schools in Shenzhen City is 5.39%, and it is higher in children aged 7 to 9 years. Boys have a higher prevalence rates of ADHD than girls. Impulsion and hyperactivity, learning and conduct disorders are common problems in children with ADHD.

[Clinical features of various subtypes of attention deficit hyperactivity disorders in children].

OBJECTIVE: To study the features of various subtypes of attention deficit hyperactivity disorders (ADHD) in children. METHODS: Sex composition, risk factors, comorbidities, intelligence quotient and behavioral problems were investigated in 175 children with ADHD who met the Diagnostic Statistical Manual of Mental Disorder Criteria (DSM-IV). The children were classified into three groups: ADHD predominantly inattentive (ADHD-I, n=82), ADHD predominantly hyperactive-impulsive (ADHD-HI, n=24) and ADHD combined type (ADHD-C, n=69). RESULTS: There were no significant differences in the sex composition among the three groups. The rates of birth abnormality in the ADHD-I and the ADHD-C groups were higher than those in the ADHD-HI group. Negative parenting practices were noted more frequently in the ADHD-HI and the ADHD-C groups than the ADHD-I group. There were no significant differences in the performance intelligence quotient (PIQ), verbal intelligence quotient (VIQ) and full intelligence quotient (FIQ) among the three groups. However, the incidence of imbalance between VIQ and PIQ in the ADHD-I group was higher than the other two groups. The rate of comorbidities with oppositional defiant disorder (ODD) and tic disorder (TD) in the ADHD-C and the ADHD-HI groups was higher than that in the ADHD-I group. Both the ADHD-I and the ADHD-C groups had a higher rate of comorbidities with learning disorder (LD) than the ADHD-HI group. The impulsive/hyperactive and conduct problems were more severe and the hyperactivity index was higher in the ADHD-C and the ADHD-HI groups than those in the ADHD-I group, while the learning difficulties in the ADHD-I group were the most severe. CONCLUSIONS: The children with ADHD-C or ADHD-HI have higher incidences of comorbidities with ODD and TD than those with ADHD-I who the learning difficulties and the imbalance between VIQ and PIQ are more severe.

[Effect of endogeneous gangliosides on integrin alpha2beta1-mediated adhesion of neuroblastoma cells to collagen].

OBJECTIVE: To study the effect of endogeneous gangliosides (Gls) on integrin alpha2beta1-mediated adhesion of neuroblastoma cells to collagen (Col). METHODS: Neuroblastoma SK-N-SH cell line was cultured in the modified eagle's medium with the presence of 10 mum D-threo-1-phenyl-2-decanolamino-3-morphinolin-1-propanol (D-PDMP), an inhibitor of glucosylceramide synthase. Flow cytometry was used to detect the expression of integrin alpha2beta1 in the cell line. The effects of Mg2(+) and monoclonal antibodies to integrin alpha2beta1 on the adhesion of the cell line to immobilized Col were observed. The adhesion cell number was measured with the BCA method and presented with absorptance A570. RESULTS: There was a high expression of integrin alpha2beta1 in the SK-N-SH cell line without D-PDMP treatment. Endogenous Gls in the cells were almost depleted after 6-day exposure to D-PDMP, but the integrin alpha2beta1 expression was not significantly changed. 1 mmoL/L Mg2(+) treatment increased significantly the number of adhesion cells in the SK-N-SH cell line. The adhesion to Col of the SK-N-SH cells exposed to D-PDMP which Gls was depleted was significantly reduced compared with the control SK-N-SH cells treated with 1 mmoL/L Mg2(+) (A570: 0.33 +/- 0.016 vs 0.57 +/- 0.033; P < 0.01). After endogeneous Gls was added into the Gls-depleted SK-N-SH cells, the adhesion of the cells was restored (A570: 0.52 +/- 0.035). The adhesion of SK-N-SH cells was significantly blocked by anti-alpha2 and anti-beta1 monoclonal antibodies, with A570 of 0.31 +/- 0.018 and 0.36 +/- 0.021 respectively. CONCLUSIONS: Endogenous tumor Gls increases neuroblastoma cell adhesion to Col by regulating the function of integrin alpha2beta1, but has no effects on the integrin expression. It is suggested that tumor Gls may play a role in migration, invasion and metastasis of tumor cells.