Biallelic SHQ1 variants in early infantile hypotonia and paroxysmal dystonia as the leading manifestation.

Biallelic SHQ1 variant-related neurodevelopmental disorder is extremely rare. To date, only six affected individuals, from four families, have been reported. Here, we report eight individuals, from seven unrelated families, who exhibited neurodevelopmental disorder and/or dystonia, received whole-genome sequencing, and had inherited biallelic SHQ1 variants. The median age at disease onset was 3.5 months old. All eight individuals exhibited normal eye contact, profound hypotonia, paroxysmal dystonia, and brisk deep tendon reflexes at the first visit. Varying degrees of autonomic dysfunction were observed. One individual had cerebellar atrophy at the initial neuroimaging study, however, three individuals showed cerebellar atrophy at follow-up. Seven individuals who underwent cerebral spinal fluid analysis all had a low level of homovanillic acid in neurotransmitter metabolites. Four individuals who received 99mTc-TRODAT-1 scan had moderate to severe decreased uptake of dopamine in the striatum. Four novel SHQ1 variants in 16 alleles were identified: 9 alleles (56%) were c.997C > G (p.L333V); 4 (25%) were c.195T > A (p.Y65X); 2 (13%) were c.812T > A (p.V271E); and 1 (6%) was c.146T > C (p.L49S). The four novel SHQ1 variants transfected into human SH-SY5Y neuronal cells resulted in a retardation in neuronal migration, suggestive of SHQ1 variant correlated with neurodevelopmental disorders. During the follow-up period, five individuals still exhibited hypotonia and paroxysmal dystonia; two showed dystonia; and one had hypotonia only. The complex interactions among movement disorders, dopaminergic pathways, and the neuroanatomic circuit needs further study to clarify the roles of the SHQ1 gene and protein in neurodevelopment.

Genotype-Phenotype Dissociation in Two Taiwanese Children with Molybdenum Cofactor Deficiency Caused by MOCS2 Mutation.

BACKGROUND: To describe the genotype-phenotype dissociation in two Taiwanese patients with molybdenum cofactor deficiency (MoCoD) caused by MOCS2 gene mutations. PATIENT DESCRIPTION: Patient 1 exhibited early-onset neurological symptoms soon after birth, followed by subsequent myoclonic seizures and movement disorder. The brain magnetic resonance imaging (MRI) showed diffuse brain injury with cystic encephalomalacia along with bilateral globus pallidi involvement, hypoplasia of corpus callosum, and cerebellar atrophy. Patient 2 had a mild phenotype with prominent movement disorder after intercurrent illness, and the brain MRI showed selective injury of the bilateral globus pallidi and the cerebellum. Both patients had markedly low levels of plasma uric acid and harbored the same MOCS2 homozygous c.16C > T mutation. Patient 1 showed chronic regression of developmental milestones and died of respiratory failure at the age of 8 years, whereas patient 2 demonstrated improvement in motor function. CONCLUSION: Genotype-phenotype dissociation could be noted in patients with MoCoD due to MOCS2 mutation. Patients with neonatal seizures, developmental delay, movement disorder, and motor regression after an illness, as well as focal or bilateral involvement of the globus pallidi on the neuroimages, should undergo biochemical testing of plasma uric acid. A pronounced plasma uric acid level is a good indicator of MoCoD. Early diagnosis can allow early provision of adequate genetic counseling.

Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders.

AIM: To investigate the diagnostic yield and treatment impact of whole-genome sequencing (WGS) in patients with paediatric neurological disorders. METHOD: From January 2016 to December 2019, paediatric patients who had suspected genetic neurological disorders were assessed using WGS. The phenotypes of eligible patients were divided into four groups: patients with neurodevelopmental disorders; patients with epilepsy; patients with neuromuscular disorders; and patients with movement disorders. RESULTS: A total of 214 consecutive patients (128 males, 86 females) underwent WGS. The mean (SD) age of disease onset was 13.8 (27.6) months (range 1d-15y 5mo). The mean (SD) age at which WGS was performed was 71.7 (58.9) months (range 8d-18y). A molecular diagnosis was reported in 43.9% of patients. The highest diagnostic rate was achieved in 62.5% of patients with neuromuscular disorders, 47.5% of patients with epilepsy, 41.1% of patients with neurodevelopment disorders, and 15.4% of patients with movement disorders. All 94 patients with a WGS diagnosis were given access to genetic counselling and 23.4% of patients had immediate changes in treatment strategies after undergoing WGS. INTERPRETATION: WGS allows paediatric neurologists to integrate genomic data into their diagnosis and adjust management strategies for a range of clinical and genetically heterogeneous disease entities to improve the clinical outcomes of patients. In our cohort, the diagnosis of a significant proportion of patients was reached through WGS (43.9%). Clinicians could use these results to directly guide the management of their patients and improve their clinical outcomes (23.4%). What this paper adds For selected children in our cohort, the diagnostic yield of whole-genome sequencing (WGS) was 43.9%. WGS can be used to expand our knowledge of phenotype-genotype variations.

Antisense oligonucleotides modulate dopa decarboxylase function in aromatic l-amino acid decarboxylase deficiency.

Aromatic l-amino acid decarboxylase deficiency (AADCD), attributed to mutations in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disease resulting from a defect in the biosynthesis of dopamine and serotonin. The DDC c.714+4A>T mutation is the most prevalent mutation among patients with AADCD, and is also a founder mutation among Taiwanese patients. In this study, the molecular consequences and function of this mutation were examined in AADCD patient-derived lymphoblastoid cells. We identified novel DDC mRNA isoforms spliced with a new exon (exon 6a) in normal and c.714+4A>T lymphoblastoid cells. In addition, we identified the SR proteins (SRSF9 and SRSF6), as well as cis-elements involved in modulating the splicing of this mutated transcript. Notably, we demonstrated that antisense oligonucleotides (ASOs) were able to restore the normal mRNA splicing and increase the level of DDC protein, as well as its downstream product serotonin, in lymphoblastoid cells derived from the patient with AADCD, suggesting that these ASOs might represent a feasible alternative strategy for gene therapy of AADCD in patients with the common c.714+4A>T mutation.

Resolving unsolved whole-genome sequencing data in paediatric neurological disorders: a cohort study.

OBJECTIVE: To resolve unsolved whole-genome sequencing (WGS) data in individuals with paediatric neurological disorders. DESIGN: A cohort study method using updated bioinformatic tools, new analysis targets, clinical information and literature databases was employed to reanalyse existing unsolved genome data. PARTICIPANTS: From January 2016 to September 2023, a total of 615 individuals who aged under 18 years old, exhibited neurological disorders and received singleton WGS were recruited. 364 cases were unsolved during initial WGS analysis, in which 102 consented to reanalyse existing singleton WGS data. RESULTS: Median duration for reanalysis after initial negative WGS results was 2 years and 4 months. The diagnostic yield was 29 of 102 individuals (28.4%) through reanalysis. New disease gene discovery and new target acquisitions contributed to 13 of 29 solved cases (44.8%). The reasons of non-detected causative variants during initial WGS analysis were variant reclassification in 9 individuals (31%), analytical issue in 9 (31%), new emerging disease-gene association in 8 (27.6%) and clinical update in 3 (10.3%). The 29 new diagnoses increased the cumulative diagnostic yield of clinical WGS in the entire study cohort to 45.5% after reanalysis. CONCLUSIONS: Unsolved paediatric WGS individuals with neurological disorders could obtain molecular diagnoses through reanalysis within a timeframe of 2-2.5 years. New disease gene, structural variations and deep intronic splice variants make a significant contribution to diagnostic yield. This approach can provide precise genetic counselling to positive reanalysis results and end a diagnostic odyssey.

Cerebellar atrophy in genetic epileptic encephalopathies: A cohort study and a systematic review.

OBJECTIVE: To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). METHODS: This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. RESULTS: The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. CONCLUSION: Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.

EGFR exon 19 in-frame deletion and polymorphisms of DNA repair genes in never-smoking female lung adenocarcinoma patients.

We explored potential associations between genetic polymorphisms in genes related to DNA repair and detoxification metabolism and epidermal growth factor receptor (EGFR) mutations in a cohort of 410 never-smoking patients with lung adenocarcinoma. Multivariate-adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CI) of EGFR mutation status in association with the genotypes of DNA repair and detoxification metabolism genes were evaluated using logistic regression analysis. We found an association between in-frame deletion in EGFR exon 19 and a single nucleotide polymorphism (SNP) rs1800566C/T located in NQO1 (aOR, 2.2 with 95% CI, 1.0-4.8) in female never-smokers. The SNP rs744154C/G in ERCC4 was also associated with the EGFR exon 19 in-frame deletion both in never-smokers (aOR, 1.7 with 95% CI, 1.0-3.0) and female never-smokers (aOR, 1.9 with 95% CI, 1.0-3.6). Although the association was marginally significant in multivariate logistic regression analysis, the A/A genotype of rs1047840 in EXO1 was associated with a 7.6-fold increase in the occurrence of the EGFR exon 19 in-frame deletion in female never-smokers. Moreover, risk alleles in NQO1, ERCC4 and EXO1 were associated with an increasing aOR of the EGFR exon 19 in-frame deletion both in never-smokers (p = 0.007 for trend) and female never-smokers (p = 0.002 for trend). Our findings suggest that the in-frame deletion in EGFR exon 19 is associated with polymorphisms in DNA repair and detoxification metabolism genes in never-smoking lung adenocarcinoma patients, especially in females.

Stromal-derived factor-1 gene variations in pediatric patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) of childhood is an autoimmune disease characterized by abnormally increased destruction of platelets and decreased megakaryopoiesis. Stromal-derived factor-1 (SDF-1) plays a role in megakaryopoiesis and may be involved in the pathogenesis of ITP. Five single nucleotide polymorphisms (SNPs) of the SDF-1 gene, including rs1801157, rs2839693, rs2297630, rs1065297, and rs266085, were assessed in 100 children with ITP and 126 healthy controls. The genotypes were analyzed by tetra ARMS polymerase chain reaction and confirmed by direct sequencing. Compared with controls, the rs2839693 A/A and rs266085 C/T genotypes were decreased in ITP patients (P = 0.004 and 0.007, respectively). The odds ratios of the latter genotypes were 0.48, 95% CI 0.28-0.82. Further analysis of the relationship between SDF-1 polymorphisms and clinical features showed that rs2297630 A/G was associated with protection from chronicity (P = 0.002; OR, 0.07; 95% CI, 0.01-0.61) and steroid dependence (P = 0.007; OR, 0.10; 95% CI, 0.01-0.84) in ITP patients. However, rs266085 genotype C/C was associated with risk of steroid dependence (P = 0.012, OR 3.87, 95% CI 1.27-11.77). The findings of this study suggest that SDF-1 gene variations may be associated with the occurrence and prognosis of childhood ITP.

Long-Term Outcome of Pediatric Patients with Anti-NMDA Receptor Encephalitis in a Single Center.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common autoimmune encephalitis in children. There is a high probability of recovery if treated promptly. We aimed to analyze the clinical features and long-term outcomes of pediatric patients with anti-NMDA receptor encephalitis. METHOD: We conducted a retrospective study with definite diagnoses of anti-NMDA receptor encephalitis in 11 children treated in a tertiary referral center between March 2012 and March 2022. Clinical features, ancillary tests, treatment, and outcomes were reviewed. RESULTS: The median age at disease onset was 7.9 years. There were eight females (72.7%) and three males (27.3%). Three (27.3%) patients initially presented with focal and/or generalized seizures and eight (72.7%) with behavioral change. Seven patients (63.6%) revealed normal brain MRI scans. Seven (63.6%) had abnormal EEG results. Ten patients (90.1%) received intravenous immunoglobulin, corticosteroid, and/or plasmapheresis. After a median follow-up duration of 3.5 years, one patient was lost to follow-up at the acute stage, nine (90%) had an mRS ≤ 2, and only one had an mRS of 3. CONCLUSIONS: With the early recognition of anti-NMDA receptor encephalitis based on its clinical features and ancillary tests, we were able to treat patients promptly with first-line treatment and achieve favorable neurological outcomes.

Intrafamilial phenotypic variability in TBC1D24-TLDc homozygous pathogenic variant-related developmental and epileptic encephalopathy.

OBJECTIVE: To describe intrafamilial phenotypic variability in rare TBC1D24-TLDc homozygous pathogenic variant-related developmental and epileptic encephalopathy (DEE). METHODS: Four individuals from two unrelated families who had been diagnosed with DEE caused by TBC1D24-TLDc homozygous c.1499C>T (p.A500V) pathogenic variant were recruited. RESULTS: The age of seizure onset ranged from 1 to 7 months. All four individuals exhibited very prolonged multifocal myoclonus or focal clonic fits, and the interictal EEGs were prone to dissociation with clinical seizures. The common precipitating factors for seizures were viral infection and fever. Two individuals from family II had progressive cerebellar atrophy: one had ataxia and the other one had no cerebellar signs clinically. All individuals had pharmaco-resistant epilepsy. However, the younger siblings of the two sibling pairs had normal neurodevelopmental outcomes. CONCLUSION: Intrafamilial phenotypic variability of cerebellar neurodegeneration on neuroimages and neurodevelopmental outcomes might be noted in individuals with TBC1D24-TLDc homozygous c.1499C>T (p.A500V) pathogenic variant-related DEE.

Clinico-Radiological Phenotype of UBTF c.628G>A Pathogenic Variant-Related Neurodegeneration in Childhood: A Case Report and Literature Review

Background: This work aims to describe the clinico-radiological phenotype of UBTF c.628G>A (p.Glu210Lys) pathogenic variant-related neurodegeneration in childhood. Methods: We describe the progress of clinical and neuroimaging features in a male individual who had childhood-onset neuroregression and carried the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant. Clinical cases reported in the literature are reviewed. Results: Fifteen individuals, from 14 reported cases and the index case, were noted. The median age at onset of neurodegeneration was 3 years. Clinical phenotype was consistent among the affected individuals, with progressive motor, speech, cognitive, and social−emotional regression together with ataxia and prominent pyramidal and extrapyramidal symptoms and signs in early to middle childhood. All individuals had the same brain MRI features in terms of symmetric and diffuse T2 high signal intensity over the bilateral subcortical, periventricular, and peritrigonal white matter and progressive cortical and subcortical supratentorial atrophy. Two individuals were reported to have bilateral thalamic involvement. All individuals had profound intellectual disability with loss of verbal and/or ambulatory functions during follow-up. Conclusions: Individuals with the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant had consistent clinical progress and neuroimaging features. Familiarity with this clinico-radiological phenotype may allow earlier diagnosis of this rare disease.

Frasier Syndrome: A Rare Cause of Refractory Steroid-Resistant Nephrotic Syndrome.

Frasier syndrome is a rare disease that affects the kidneys and genitalia. Patients who have Frasier syndrome develop nephrotic syndrome (NS) featuring focal segmental glomerulosclerosis (FSGS) that is resistant to steroid treatment in early childhood. Male patients can have female external genitalia (pseudo-hermaphroditism) at birth and develop gonado-blastoma in their adolescence. Frasier syndrome is caused by mutations in the splice donor site at intron 9 of the Wilms' tumor WT1 gene; these mutations result in an imbalanced ratio of WT1 protein isoforms and affect the development of the urogenital tract, podocyte function, and tumor suppression. Here, we report on a patient with long-term refractory NS who developed a malignant mixed germ cell tumor arising in a gonado-blastoma of the ovary 8 years after the onset of proteinuria.

Depression and suicide risk in hemodialysis patients with chronic renal failure.

BACKGROUND: Depression and suicide are well established as prevalent mental health problems for patients on hemodialysis. OBJECTIVE: The authors examined the demographic and psychological factors associated with depression among hemodialysis patients and elucidated the relationships between depression, anxiety, fatigue, poor health-related quality of life, and increased suicide risk. METHOD: This cross-sectional study enrolled 200 end-stage renal disease patients age ≥18 years on hemodialysis. Psychological characteristics were assessed with the Mini-International Neuropsychiatric Interview, the Hospital Anxiety and Depression Scale, the short-form Health-Related Quality of Life Scale, and Chalder Fatigue Scale, and structural equation modeling was used to analyze the models and the strength of relationships between variables and suicidal ideation. RESULTS: Of the 200 patients, 70 (35.0%) had depression symptoms, and 43 (21.5%) had had suicidal ideation in the previous month. Depression was significantly correlated with a low body mass index (BMI) and the number of comorbid physical illnesses. Depressed patients had greater levels of fatigue and anxiety, more common suicidal ideation, and poorer quality of life than nondepressed patients. Results revealed a significant direct effect for depression and anxiety on suicidal ideation. CONCLUSION: Among hemodialysis patients, depression was associated with a low BMI and an increased number of comorbid physical illnesses. Depression and anxiety were robust indicators of suicidal ideation. A prospective study would prove helpful in determining whether early detection and early intervention of comorbid depression and anxiety among hemodialysis patients would reduce suicide risk.

Electroclinical variability of pyridoxine-dependent epilepsy caused by ALDH7A1 gene mutations in four Taiwanese children.

BACKGROUND: The aim of this study was to describe the electroclinical variability of four Taiwanese patients with pyridoxine-dependent epilepsy (PDE) caused by ALDH7A1 gene mutations. METHODS: Demographic data, case histories, clinical seizure patterns, EEG features, neuroimaging findings, ALDH7A1 gene mutations, treatments, and neurodevelopmental outcomes of the four patients were collected and analyzed. RESULTS: The four patients exhibited the first symptom between the ages of 6 days and 11 months. The age of diagnosis was between 2 months and 13 years 8 months. Patient 1 exhibited classical phenotype of PDE, neonatal onset epileptic encephalopathy. Patient 2 showed atypical phenotypes of intractable epilepsy with additional neurological and abdominal symptoms. Patients 3 and 4, who had normal neurodevelopment, had familial epilepsy with fever sensitivity. Patients 2, 3, and 4 had atypical phenotypes and showed seizure exacerbation during febrile infections. EEG features of patient 1 revealed alternating rhythmic discharges followed by electrodecremental episodes; while those of patients 2, 3, and 4 disclosed nonspecific findings or normal results. Administration of oral pyridoxine hydrochloride resulted in seizure cessation in patients 1, 3, and 4, and they achieved normal neurodevelopmental outcomes, but intractable epilepsy and profound mental retardation occurred in patient 2 as he was not diagnosed until he was 13 years and 8 months old. CONCLUSION: Electroclinical features of PDE vary widely, including patients with normal neurodevelopment and normal or nonspecific EEG findings. To avoid delay in treatment, a therapeutic trial with pyridoxine hydrochloride should be performed in all cases of neonatal, infantile, and childhood refractory epilepsy until ALDH7A1 gene mutation-related PDE has been excluded. Pyridoxine treatment may show clinical effectiveness even in a relatively late stage, i.e., age older than one year.

Respiratory presentation of patients infected with enterovirus D68 in Taiwan.

BACKGROUND: Enterovirus-D68 (EV-D68) has been endemic in Taiwan for some years with a small number of positive cases. Detailed information about respiratory presentation is lacking. This study characterized the clinical course in children admitted to the medical center and regional hospital in Taichung during 2015. METHODS: Retrospective chart review of patients with confirmed EV-D68 infection admitted to the medical center and regional hospital in Taichung with respiratory symptoms in the second half of 2015. Past medical history, clinical presentation, management, and course in hospital were collected and analyzed. Simple demographic data and clinical symptoms were also collected from patients confirmed with EV-D68 infection who visited clinics in Taichung. RESULTS: Six children were included. Two patients had a prior history of asthma or recurrent dyspnea, and one had other preexisting medical comorbidities. One child was admitted to the pediatric intensive care unit. All the patients were cured. Cough, rhinorrhea, tachypnea and fever were the most common clinical symptoms among inpatients, while influenza-like illness (ILI) was prevalent in outpatients. CONCLUSION: EV-D68 infection resulted in respiratory presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of asthma or recurrent dyspnea appear to be more severely affected.

Leigh syndrome: clinical and neuroimaging follow-up.

Leigh syndrome, caused by dysfunction in mitochondrial energy metabolism, is an inherited, heterogeneous, and progressive neurodegenerative disorder of infancy and childhood. From 1983 to August 2006, 14 cases diagnosed with Leigh syndrome were studied in terms of characteristic neuroimaging findings and abnormal mitochondrial configurations under electron microscopy, as well as molecular analysis. Of the 14 cases, 11 presented clinical features before age 1 (79%). All 14 presented with variable symptoms of central nervous system involvement. The three most common symptoms were developmental delay (12/14; 86%), seizures (11/14; 79%), and altered consciousness (8/14; 57%). Extra-central nervous system manifestations were observed in 10 of the 14 cases, the most common symptoms being failure to thrive (5/14; 36%), pericardial effusion and dilated cardiomyopathy (3/14; 21%), and liver function impairment (3/14; 21%). In all 14 cases, neuroimaging revealed abnormal findings over the basal ganglion, brainstem, or both. The putamen was the most common lesion site in the basal ganglia (11/12; 92%). Cranial magnetic resonance imaging was used for follow-up in 6 cases because of changes in clinical features; in all 6 cases the imaging revealed evolution in the brain. Cranial magnetic resonance spectroscopy was performed in 3 cases and in 2 of them revealed lactate peaks during deterioration of the disease course. The prognosis for Leigh syndrome was poor during long-term follow-up. Seven cases were early fatalities, before 1 year and 6 months of age. Follow-up cranial magnetic resonance imaging together with magnetic resonance spectroscopy in cases with clinical evolution is helpful for monitoring this disease.

Do serological tests provide adequate rapid diagnosis of Mycoplasma pneumoniae infection?

This study was designed to evaluate the serologic response to Mycoplasma pneumoniae infection. A total of 589 children < or =18 years (190 in the year 2004; 399 in 2005) and 2,073 adults > or = 18 years of age (980 in the year 2004; 1,093 in 2005) with respiratory symptoms underwent serological testing for M. pneumoniae infection. The tests included passive particle agglutination (PA) and enzyme-linked immunosorbent assay (ELISA). The seroprevalence rates of M. pneumoniae infection in the years 2004 and 2005 were 6.9 and 10.1%, respectively. The seropositivity rate was significantly higher in children (29.6% in 2005; 23.7% in 2004) than in adults (2.9% in 2005; 3.7% in 2004) (odds ratio, 8.138 in 2004; 13.923 in 2005; 95% confidence interval, 5.077-13.045 in 2004; 9.220-21.026 in 2005). Paired sera for the PA test were obtained from 32 of 399 children, and 22 of them demonstrated at least fourfold rises in antibody titer. ELISA had a sensitivity of 77.3% and a specificity of 40.0%; PA had a sensitivity of 9.5% and a specificity of 80%. The ELISA test was superior to the PA test in diagnosing acute M. pneumoniae infection in children. Both tests were significantly more sensitive when they were performed 1 week after the onset of infection.

The neurological evolution of Pearson syndrome: case report and literature review.

BACKGROUND: Pearson syndrome (PS) is an uncommon specific syndrome among mitochondrial diseases. It has unique clinical presentations. AIMS: The purpose of this article is to clarify the neurological evolution, neuroimage findings, molecular genetic analysis and outcomes in PS cases with neurologic manifestations. METHODS: We described the clinical progress of a female patient who was diagnosed as PS with a novel 6.0 kbp mitochondrial DNA deletion. She had typical clinical features of PS in early infancy followed by multiple organs involvement after the age of 1 year. At age 3, Kearns-Sayre syndrome (KSS) and Leigh syndrome (LS) developed. We also reviewed PS cases reported in the literature and analyzed the neurological evolution. RESULTS: Total 55 PS cases, including our index case, had been reported. Among them, 11 cases had detailed clinical descriptions in terms of hypotonia, developmental delay, ataxia or tremor. In whom, PS might evolve into KSS and/or LS: three cases evolving into KSS; one case on the transition of KSS; three cases evolve into LS; our index case has both presentations. The neuroimage findings of PS were quite different which might be from normal to specific abnormal findings over the cerebral white matter, cerebellum, basal ganglion and brainstem. Among those cases, the molecular analysis revealed large-scale mitochondrial deletion around 3.1-6.0kbp. The outcome of PS was opposite: either early death before age 4 or survived beyond age 7. CONCLUSIONS: The neurological features of PS have potential evolution changes that are from normal, mild neurological deficits to special mitochondrial syndromes: KSS and LS. Closely monitoring neurological symptoms, arranging eye fundus examinations and neuroimaging studies in cases with changes of neurological signs are crucial.

Rapid diagnosis of Mycoplasma pneumoniae infection in children by polymerase chain reaction.

BACKGROUND AND PURPOSE: Endemic atypical pneumonia was noted in central Taiwan during 2005. The serological response to Mycoplasma pneumoniae infection was usually poor in its early course; convalescent serum was needed in most cases, which was sometimes difficult to obtain in children. Empiric antimicrobial therapy was usually initiated before serological testing. A rapid test would be useful to define the etiology and initiate appropriate management. We studied the usefulness of polymerase chain reaction (PCR) analysis for diagnosis in this setting. METHODS: This 1-year prospective study conducted during 2005 in central Taiwan enrolled 307 hospitalized children (aged 3 months to 16 years) with respiratory tract infections, some complicated with systemic manifestations, such as encephalitis and skin rash. Fifty one patients were excluded due to unavailability of data or lack of consent. PCR analysis of samples using a primer set for the P1 gene of M. pneumoniae was compared to serological testing, including particle agglutinin test and enzyme-linked immunosorbent assay. RESULTS: 263 throat swabs from 256 patients were available for PCR tests, and serological tests were performed in 140 children (55%) with clinical suspicion of atypical pneumonia. Eighty two children (32%) were positive by the PCR method and 76 (30%) were serologically positive. Seventy one patients (87%) with duration of disease onset of 2 to 7 days had positive PCR results. The mean age of patients with M. pneumoniae infection was 5.2 years, with 27% of patients <2 years old and 73% of patients >2 years of age. The diagnoses were as follows: pneumonia (n = 44); pneumonia complicated with pleural effusion (n = 12); bronchitis and bronchopneumonia (n = 18); asthmatic bronchitis (n = 2); croup syndrome (n = 1); pharyngitis (n = 3); and herpangina (n = 2). Coinfection with bacteria or virus was found in 21% of patients with M. pneumoniae infection. CONCLUSIONS: The PCR method could provide earlier diagnosis of M. pneumoniae infection and was useful to identify variable clinical features of infection, especially in younger children.

Early cardiac involvement in an infantile Sandhoff disease case with novel mutations.

INTRODUCTION: Hepatosplenomegaly is often present in infantile Sanshoff disease. However, cardiac involvement is extremely uncommon. CASE REPORT: We describe a 14-month-old female baby who exhibited mitral regurgitation and cardiomegaly at the age of 2months, dilation of the left atrium and left ventricle at age of 6months, followed by regression of developmental milestones after an episode of minor infection at age of 14months. Brain magnetic resonance imaging revealed signal changes over the bilateral thalami, bilateral cerebral white matter and left putamen. An examination of the fundus showed presence of cherry-red spots in both macular areas. The lysosomal enzymatic activities showed a marked reduction of ß-hexosaminidase B (HEXB) activity. Two novel mutations of HEXB gene were identified. One of the mutations was a c.1538 T>C mutation, which predicted a p.L513P amino acid substitution of leucine to proline; the other was a c.299+5 G>A mutation, which was a splice site mutation. CONCLUSION: Cardiac involvement might occur prior to neurological symptoms in infantile Sandhoff disease, and it should be included in the differential diagnoses of metabolic cardiomyopathies in the infantile stage.