ABSTRACT
In pleiotropic diseases, multiple organ systems are affected causing a variety of clinical manifestations. Here, we report a pleiotropic disorder with a unique constellation of neurological, endocrine, exocrine, and haematological findings that is caused by biallelic MADD variants. MADD, the mitogen-activated protein kinase (MAPK) activating death domain protein, regulates various cellular functions, such as vesicle trafficking, activity of the Rab3 and Rab27 small GTPases, tumour necrosis factor-α (TNF-α)-induced signalling and prevention of cell death. Through national collaboration and GeneMatcher, we collected 23 patients with 21 different pathogenic MADD variants identified by next-generation sequencing. We clinically evaluated the series of patients and categorized the phenotypes in two groups. Group 1 consists of 14 patients with severe developmental delay, endo- and exocrine dysfunction, impairment of the sensory and autonomic nervous system, and haematological anomalies. The clinical course during the first years of life can be potentially fatal. The nine patients in Group 2 have a predominant neurological phenotype comprising mild-to-severe developmental delay, hypotonia, speech impairment, and seizures. Analysis of mRNA revealed multiple aberrant MADD transcripts in two patient-derived fibroblast cell lines. Relative quantification of MADD mRNA and protein in fibroblasts of five affected individuals showed a drastic reduction or loss of MADD. We conducted functional tests to determine the impact of the variants on different pathways. Treatment of patient-derived fibroblasts with TNF-α resulted in reduced phosphorylation of the extracellular signal-regulated kinases 1 and 2, enhanced activation of the pro-apoptotic enzymes caspase-3 and -7 and increased apoptosis compared to control cells. We analysed internalization of epidermal growth factor in patient cells and identified a defect in endocytosis of epidermal growth factor. We conclude that MADD deficiency underlies multiple cellular defects that can be attributed to alterations of TNF-α-dependent signalling pathways and defects in vesicular trafficking. Our data highlight the multifaceted role of MADD as a signalling molecule in different organs and reveal its physiological role in regulating the function of the sensory and autonomic nervous system and endo- and exocrine glands.
Subject(s)
Death Domain Receptor Signaling Adaptor Proteins/genetics , Developmental Disabilities/genetics , Guanine Nucleotide Exchange Factors/genetics , Nervous System Diseases/genetics , Humans , Mutation , Phenotype , Protein Transport/genetics , Signal Transduction/geneticsABSTRACT
INTRODUCTION: Although intrathecal baclofen (ITB) therapy is an effective treatment for spasticity, it has several disadvantages and a risk of complications. METHODS: We present six pediatric patients who suffered from unusual mechanical failures of intrathecal baclofen pump systems. RESULTS: With these case-vignettes, we provide a systematic approach on how to interpret the symptoms of ITB complications and an advice which further diagnostic and therapeutic steps to follow. We underline the seriousness of baclofen overdose, underdosing or withdrawal.
Subject(s)
Cerebral Palsy , Muscle Relaxants, Central , Baclofen/therapeutic use , Cerebral Palsy/drug therapy , Child , Humans , Infusion Pumps, Implantable , Injections, Spinal , Muscle Relaxants, Central/therapeutic use , Muscle Spasticity/drug therapyABSTRACT
The SET domain containing 2, histone lysine methyltransferase encoded by SETD2 is a dual-function methyltransferase for histones and microtubules and plays an important role for transcriptional regulation, genomic stability, and cytoskeletal functions. Specifically, SETD2 is associated with trimethylation of histone H3 at lysine 36 (H3K36me3) and methylation of α-tubulin at lysine 40. Heterozygous loss of function and missense variants have previously been described with Luscan-Lumish syndrome (LLS), which is characterized by overgrowth, neurodevelopmental features, and absence of overt congenital anomalies. We have identified 15 individuals with de novo variants in codon 1740 of SETD2 whose features differ from those with LLS. Group 1 consists of 12 individuals with heterozygous variant c.5218C>T p.(Arg1740Trp) and Group 2 consists of 3 individuals with heterozygous variant c.5219G>A p.(Arg1740Gln). The phenotype of Group 1 includes microcephaly, profound intellectual disability, congenital anomalies affecting several organ systems, and similar facial features. Individuals in Group 2 had moderate to severe intellectual disability, low normal head circumference, and absence of additional major congenital anomalies. While LLS is likely due to loss of function of SETD2, the clinical features seen in individuals with variants affecting codon 1740 are more severe suggesting an alternative mechanism, such as gain of function, effects on epigenetic regulation, or posttranslational modification of the cytoskeleton. Our report is a prime example of different mutations in the same gene causing diverging phenotypes and the features observed in Group 1 suggest a new clinically recognizable syndrome uniquely associated with the heterozygous variant c.5218C>T p.(Arg1740Trp) in SETD2.
Subject(s)
Genetic Predisposition to Disease , Histone-Lysine N-Methyltransferase/genetics , Intellectual Disability/genetics , Neurodevelopmental Disorders/genetics , Tubulin/genetics , Child , Child, Preschool , Codon/genetics , Epigenesis, Genetic/genetics , Female , Genetic Association Studies , Humans , Infant , Intellectual Disability/pathology , Loss of Function Mutation/genetics , Male , Mutation, Missense , Nervous System Malformations/genetics , Nervous System Malformations/pathology , Neurodevelopmental Disorders/physiopathologyABSTRACT
In trisomy 9 mosaicism, plexus hypertrophy has been described as a phenotypical feature and cause of hydrocephalus. We report on a 15-month-old child with hydrocephalus and trisomy 9 mosaicism primarily diagnosed in amniocentesis. After implantation of a ventriculoperitoneal shunt and subsequent revision, he presented with an exhaustion of peritoneal absorption leading to massive ascites. The implantation of a peritoneal drainage offered the unique opportunity to monitor cerebrospinal fluid (CSF) production indirectly via abdominal CSF drainage. In an individual trial, we performed endoscopic choroid plexus cauterization to reduce cerebrospinal fluid production, which failed to reduce excessive CSF production. In a second procedure, a ventriculoatrial shunt was implanted and succeeded to treat persistent hydrocephalus.
Subject(s)
Choroid Plexus , Hydrocephalus , Child , Choroid Plexus/diagnostic imaging , Choroid Plexus/surgery , Chromosomes, Human, Pair 9 , Humans , Hydrocephalus/complications , Hydrocephalus/surgery , Infant , Male , Mosaicism , Trisomy/genetics , Uniparental DisomyABSTRACT
This article reports on a previously healthy 17-month-old boy who developed pulmonary mucormycosis after a near-drowning incident in a goose pond. The patient survived without neurological sequelae and recovered, under treatment with amphotericin B, from the rare and often invasive fungal infection with Rhizopus spp., usually occurring in immunodeficient patients.
Subject(s)
Lung Diseases, Fungal , Mucormycosis , Near Drowning , Rhizopus , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Humans , Infant , MaleABSTRACT
INTRODUCTION: Malaria is a widespread mosquito-borne infectious disease with over 300 million cases and roughly 900 thousand deaths in 2013. Cerebral involvement of malaria causes 50 % of all infection-associated deaths, especially in children below the age of 5 years. Hydrocephalus is a medical condition with abnormal accumulation of cerebrospinal fluid in physiological cavities and ventricles. Standard treatment is the implantation of a cerebrospinal fluid shunt device. A common problem associated with shunt treatment especially in pediatric patients is infection and consecutive shunt dysfunction caused by bacteriae or high protein levels clogging the valve. In these cases, Staphylococcus aureus and Staphylococcus epidermidis are predominantly found in CSF cultures. CASE PRESENTATION: We present a case of a 2-year old boy from Saudi Arabia with a ventriculoperitoneal (VP)-shunt-dependent congenital hydrocephalus who suffered from cerebral malaria and developed consecutive shunt failure. CONCLUSION: To the best of our knowledge, shunt failure caused by malaria CNS infection with Plasmodium falciparum has not yet been reported in the literature and should be considered as a rare cause of VP-shunt failure in patients with atypical VP-shunt infections living in or traveling from endemic areas.
Subject(s)
Central Nervous System Infections , Malaria/complications , Ventriculoperitoneal Shunt/adverse effects , Central Nervous System Infections/complications , Central Nervous System Infections/etiology , Central Nervous System Infections/parasitology , Cerebral Ventricles/surgery , Child, Preschool , Humans , Malaria/pathology , MaleABSTRACT
Cystic fibrosis (CF) is an inherited disease with a defect in epithelial chloride transport that results in a multisystem disease. Although pulmonary disease remains the primary cause of morbidity and mortality, focal biliary cirrhosis and portal hypertension may develop in up to 8% of these patients. Liver transplantation (TX) is an accepted therapy and shows good results. We report on a patient with cystic fibrosis homozygous for the most common CFTR mutation delta F 508 who received a combined heterotopic liver and pancreas transplantation at the age of 18 yr. He suffered from CFRD, which untypically required high doses of insulin. In addition, the patient had pulmonary complications, was chronically colonized with multiresistant Pseudomonas aeruginosa (MBL) and had an allergic bronchopulmonary aspergillosis (ABPA). The patient remained in stable health for 54 months post-TX and was able to live a nearly normal life. With a follow-up of five yr, the function of the liver and pancreas allografts was excellent. However, and sadly, his pulmonary function continued to deteriorate from progression of his CF, and he died of respiratory failure due to a severe pneumonia and septicemia at the age of 23 yr and five months.
Subject(s)
Cystic Fibrosis/therapy , Diabetes Mellitus/therapy , Liver Transplantation/methods , Pancreas Transplantation/methods , Aspergillosis, Allergic Bronchopulmonary/complications , Cystic Fibrosis/complications , Diabetes Complications/therapy , Disease Progression , Fatal Outcome , Graft Survival , Humans , Lung Diseases/microbiology , Male , Pseudomonas Infections/complications , Pseudomonas Infections/therapy , Pseudomonas aeruginosa , Young AdultABSTRACT
Fatal and nonfatal drowning are among the leading causes of death and lifelong severe neurological impairment among children and adolescents. This study aimed to complement research from Leipzig 1994-2008 to seek trends within risk factors, treatments, and outcomes throughout the last decade. We retrospectively investigated data of 47 inpatients aged 0-18 admitted to Leipzig University Department of Pediatrics who matched ICD-10 code T75.1 from 2008 to 2020 and compared them to a preceding study at the same institution. We also examined the prognostic value of parameters regarding the patients' outcomes. There were three median incidents per annum. The median age was 2.75 years; 76% of incidents happened in males. An accumulation was seen during the summer months and weekends. Most drowning incidents occurred in private ponds or pools (48.9%). Thirty-nine children were discharged without resulting morbidity, four showed neurological impairment, and three died. Risk factors concerning age, sex, and incident characteristics were confirmed. Special supervision needs still apply to 1-3-year-old male children or children with pre-existing health conditions around private pools and ponds. Hospitalization duration shortened, and morbidity and lethality decreased since the previous study. There was structural improvement in primary care and medical documentation. Parameters suggesting good outcomes include a submersion time < 5 min, GCS > 3 points, spontaneous movement upon admission, remaining pupillary light response, the absence of cardiovascular arrest, body temperature ≥ 32 °C, pH > 7, blood glucose < 15 mmol/L, lactate < 14 mmol/L, base excess ≥ -15 mmol/L, and the absence of ARDS. Clear legislation can contribute to improved private home water safety. Further studies should include a broad in- and outpatient spectrum and standardized incident documentation presupposing Utstein-style reporting. Regular reinvestigation of consistent geographical regions facilitates process evaluations of drowning epidemiology and therapy evolution.
ABSTRACT
BACKGROUND: Children treated in a pediatric intensive care unit (PICU) often receive several drugs together, among them drugs defined as high-alert medications (HAMs). Those drugs carry a high risk of causing patient harm, for example, due to a higher potential for interactions. HAMs should therefore be administered with caution, especially in a PICU. OBJECTIVES: The objective of the current study was to identify drug-drug interactions involving HAMs that increase the risk of interaction-associated symptoms in pediatric intensive care. METHODS: In a retrospective study, we analyzed the electronic documentation of patients hospitalized for at least 48 h in a general PICU who received at least two different drugs within a 24-h interval. We assessed potential drug-drug interactions involving HAM on the basis of the two drug information databases UpToDate and drugs.com. Furthermore, we analyzed whether symptoms were observed after the administration of drug pairs that could lead to interaction-associated symptoms. For drug pairs involving HAM administered on at least 2% of patient days, and symptoms observed at least ten times after a respective drug pair, we calculated odds ratios, 95% confidence intervals, and p-values by using a univariate binary logistic regression. RESULTS: Among 315 analyzed patients, 81.3% (256/315) received drugs defined as high-alert medication for pediatric patients. Those high-alert medications were involved in 20,150 potential drug-drug interactions. In 14.0% (2830/20,150) of these, one or more symptoms were observed that could be a possible consequence of the interaction, resulting in 3203 observed symptoms affecting 56.3% (144/256) of patients receiving high-alert medication. The odds ratios for symptoms observed after a drug-drug interaction were increased for eight specific symptoms (each p ≤ 0.05), especially hemodynamic alterations and disturbances of electrolyte and fluid balance. The odds ratio was highest for decreased blood pressure observed after the administration of the drug pair fentanyl and furosemide (OR 5.06; 95% confidence interval 3.5-7.4; p < 0.001). Increased odds ratios for specific symptoms observed after drug-drug interactions resulted from eight combinations composed of eight different drugs: digoxin, fentanyl, midazolam, phenobarbital, potassium salts and vancomycin (high-alert medications), and the diuretics furosemide and hydrochlorothiazide (non-high-alert medications). The resulting drug pairs were: potassium salts-furosemide, fentanyl-furosemide, vancomycin-furosemide, digoxin-furosemide, digoxin-hydrochlorothiazide, fentanyl-phenobarbital, potassium salts-hydrochlorothiazide, and midazolam-hydrochlorothiazide. CONCLUSIONS: In a cohort of PICU patients, this study identified eight specific drug pairs involving high-alert medications that may increase the risk of interaction-associated symptoms, mainly hemodynamic alterations and electrolyte/fluid balance disturbances. If the administration of those drug pairs is unavoidable, patients should be closely monitored.
Subject(s)
Drug Interactions , Intensive Care Units, Pediatric , Humans , Retrospective Studies , Child , Male , Child, Preschool , Female , Infant , Adolescent , Drug-Related Side Effects and Adverse Reactions/epidemiologyABSTRACT
The tricarboxylic acid (TCA) cycle represents the key enzymatic steps in cellular energy metabolism. Once the TCA cycle is impaired in case of inherited metabolic disorders, life-threatening episodes of metabolic decompensation and severe organ failure can arise. We present the case of a 6 ½-year-old girl with propionic acidaemia during an episode of acute life-threatening metabolic decompensation and severe lactic acidosis. Citric acid given as an oral formulation showed the potential to sustain the TCA cycle flux. This therapeutic approach may become a treatment option in a situation of acute metabolic crisis, possibly preventing severe disturbance of energy metabolism.
Subject(s)
Citric Acid Cycle/drug effects , Citric Acid/therapeutic use , Propionic Acidemia/drug therapy , Propionic Acidemia/metabolism , Acute Disease , Anticoagulants/therapeutic use , Child , Critical Illness , Energy Metabolism/drug effects , Female , Humans , Treatment OutcomeABSTRACT
BACKGROUND: Owing to complex treatment, critically ill children may experience alterations in their vital parameters. We investigated whether such hemodynamic alterations were temporally and causally related to drug therapy. METHODS: In a university pediatric intensive care unit, we retrospectively analyzed hemodynamic alterations defined as values exceeding the limits set for heart rate (HR) and blood pressure (BP). For causality assessment, we used the World Health Organization-Uppsala Monitoring Center (WHO-UMC) system, which categorizes the probability of causality as "certain," "probable," "possible," and "unlikely." RESULTS: Of 315 analyzed patients with 43,200 drug prescriptions, 59.7% experienced at least one hemodynamic alteration; 39.0% were affected by increased HR, 19.0% by decreased HR, 18.1% by increased BP, and 16.2% by decreased BP. According to drug information databases, 83.9% of administered drugs potentially lead to hemodynamic alterations. Overall, 88.3% of the observed hemodynamic alterations had a temporal relation to the administration of drugs; in 80.2%, more than one drug was involved. Based on the WHO-UMC system, a drug was rated as a "probable" causing factor for only 1.4% of hemodynamic alterations. For the remaining alterations, the probability ratings were lower because of multiple potential causes, e.g., several drugs. CONCLUSIONS: Critically ill children were frequently affected by hemodynamic alterations. The administration of drugs with potentially adverse effects on hemodynamic parameters is often temporally related to hemodynamic alterations. Hemodynamic alterations are often multifactorial, e.g., due to administering multiple drugs in rapid succession; thus, the influence of individual drugs cannot easily be captured with the WHO-UMC system.
Subject(s)
Critical Illness , Drug-Related Side Effects and Adverse Reactions , Humans , Child , Blood Pressure , Heart Rate , Retrospective Studies , Critical CareABSTRACT
Following the extensive non-pharmaceutical interventions (NPIs) and behavioral changes in the wake of the SARS-CoV-2 pandemic, an interseasonal rise in respiratory syncytial virus (RSV) cases was observed in Germany in 2021. The aim of this study was to characterize the local molecular epidemiology of RSV infections in comparison to the three pre-pandemic seasons. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of RSV infections. RSV detections peaked in calendar week 40 of 2021, 18 weeks earlier than the usual peak observed in the three pre-pandemic seasons. Sequence analysis revealed a close phylogenetic relatedness regardless of the season of origin. A significantly higher amount of pediatric cases (88.9% of all cases, p < 0.001) was observed for season 2021/2022. For the pediatric cases, significant differences were observed for an increased number of siblings in the household (p = 0.004), a lower rate of fever (p = 0.007), and a reduced amount of co-infections (p = 0.001). Although the mean age of the adult patients was significantly younger (47.1 vs. 64.7, p < 0.001), high rates of comorbidities, lower respiratory tract infections and intensive care unit admissions prevailed. The NPIs in the wake of the SARS-CoV-2 pandemic had a tremendous impact on the epidemiologic characteristics and seasonality of RSV and warrant further epidemiologic studies of this important pathogen.
Subject(s)
COVID-19 , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Adult , Humans , Child , Seasons , SARS-CoV-2/genetics , Pandemics/prevention & control , Phylogeny , Tertiary Care Centers , COVID-19/epidemiology , COVID-19/prevention & control , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/prevention & control , Germany/epidemiologyABSTRACT
Vascular access in severely injured pediatric trauma patients is associated with time-critical circumstances and low incidences, whereas only scarce literature on procedure performance is available. The purpose of this study was to analyze the performance of different vascular access procedures from the first contact at the scene until three hours after admission. Intubated pediatric trauma patients admitted from the scene to a single Level I trauma center between 2008 and 2019 were analyzed regarding intravenous (IV) and intraosseous (IO) accesses, central venous catheterization (CVC) and arterial line placement. Sixty-five children with a median age of 14 years and median injury severity score of 29 points were included, of which 62 (96.6%) underwent successful prehospital IV or IO access by emergency medical service (EMS) physicians, while it failed in two children (3.1%). On emergency department (ED) admission, IV cannulas of prehospital EMS had malfunctions or were dislodged in seven of 55 children (12.7%). IO access was performed in 17 children without complications, and was associated with younger age, higher injury severity and higher mortality. Fifty-two CVC placements (58 attempts) and 55 arterial line placements (59 attempts) were performed in 45 and 52 children, respectively. All CVC and arterial line placements were performed in the ED, operating room (OR) and intensive care unit (ICU). Ten mechanical complications related to CVC placement (17.8%) and seven related to arterial line placement (10.2%) were observed, none of which had outcome-relevant consequences. This case series suggests that mechanical issues of vascular access may frequently occur, underlining the need for special preparedness in prehospital, ED, ICU and OR environments.
ABSTRACT
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and its prognosis has considerably improved over the past 2 decades due to new therapeutic approaches. In some cases, however, it can develop very rapidly and cause possibly fatal complications. We report on the case of an 11-year-old boy with ALL, who rapidly developed severe lactic acidosis and abdominal compartment syndrome. He died of multiorgan failure only 5 days after diagnosis of ALL had been established. Autopsy revealed systemic leukemic infiltrations. We suppose that the mass of tumor cells induced a cascade of metabolic and endocrine reactions, which not only triggered the rapid progression of the disease but were also accountable for the lack of response to treatment. The pathophysiology of abdominal compartment syndrome as a rare and in our case ultimately fatal complication of ALL is described.
Subject(s)
Acidosis, Lactic/etiology , Intra-Abdominal Hypertension/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Acidosis, Lactic/physiopathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Fatal Outcome , Humans , Intra-Abdominal Hypertension/physiopathology , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology , Randomized Controlled Trials as TopicABSTRACT
Congenital mature teratomas of the umbilical cord are extremely rare. We report on a girl who presented with a ruptured omphalocele and a 7 cm mass connected to the umbilicus, which we resected on the first day of life. Histology revealed mature umbilical cord teratoma . On the 29th day of life, a secondary laparotomy was necessary to address the associated intestinal malformations (megaduodenum, stenotic small bowel with duplication and malrotation). After a prolonged hospital stay, we discharged the patient in age-appropriate conditions. Antenatal diagnosis of an umbilical cord tumor can be challenging in the presence of an omphalocele. Given the high prevalence of associated malformations, the finding of umbilical cord teratoma should be followed by a detailed and comprehensive neonatal workup for additional abnormalities.
ABSTRACT
Inadvertent tracheal tube misplacement and particularly endobronchial intubation are well-known complications of emergency endotracheal intubation (ETI) in pediatric trauma patients, which require repositioning of the tube to avoid impairment of gas exchange. The main aim of study was to identify the frequency of tube misplacement and associated factors of pediatric trauma patients who received ETI either by prehospital physician-staffed emergency medical service (EMS), or at emergency department (ED) admission to a single level-1 trauma center. Sixty-five patients (median age 14 years and median injury severity score 29) were included. Of these, 30 underwent helicopter EMS ETI, 29 ground EMS ETI, and 6 ED ETI. Seventeen cases (26%) of tracheal tube misplacement were recognized. After multivariable analysis, tracheal tube misplacement was independently negatively associated with body weight (OR 0.86; 95% CI, 0.76-0.99; p = 0.032) and helicopter EMS ETI (OR 0.20; 95% CI, 0.04-0.97; p = 0.036). Two of nineteen patients received tube thoracostomy due to endobronchial intubation. Mortality and length of stay were comparable in patients with misplaced tubes and correctly placed tubes. The results suggest that particularly small children require attention to avoid tracheal tube misplacement, which emphasizes the need for special training. Helicopter EMS physicians' expertise might be beneficial in prehospital pediatric trauma patients requiring advanced airway management.
ABSTRACT
Epidermal nevus syndromes encompass a highly heterogeneous group of systemic disorders, characterized by epidermal nevi, and a spectrum of neuromuscular, ocular, and bone abnormalities. Cutaneous-skeletal hypophosphatemia syndrome (CSHS) constitutes a specific sub-entity in which elevated levels of fibroblast growth factor-23 cause hypophosphatemic rickets that are, to date, not amenable to causal therapy. Here, we report the first long-term follow-up of causal treatment with burosumab in a 3-year-old female patient with CSHS. 4 weeks after initiation of burosumab treatment, serum phosphate normalized to age-appropriate levels. Furthermore, long-term follow-up of 42 months revealed significant improvement of linear growth and gross physical functions, including respiratory insufficiency. Radiographic rickets severity as well as subjective bone pain were strongly reduced, and no side effects were observed over the course of treatment. In summary, we, here, report about a successful treatment of hypophosphatemic rickets in CSHS with burosumab over the time course of 42 months. In our patient, burosumab showed convincing efficacy and safety profile, without any loss of effect or increase of dose.
Subject(s)
Familial Hypophosphatemic Rickets , Hypophosphatemia , Rickets, Hypophosphatemic , Antibodies, Monoclonal, Humanized , Child, Preschool , Familial Hypophosphatemic Rickets/complications , Familial Hypophosphatemic Rickets/drug therapy , Female , Humans , Hypophosphatemia/chemically induced , Hypophosphatemia/drug therapy , SyndromeABSTRACT
Constitutional partial trisomy 11q in man mostly occurs in combination with partial trisomy 22 due to a balanced parental translocation t(11;22). Occasionally a chromosome other than 22 is involved in the parental translocation with chromosome 11, resulting in partial monosomy for the other participating chromosome. We report of a patient with partial trisomy 11q and partial monosomy 10p [46,XX,der(10)t(10;11)(p15;q22)] due to a paternal balanced translocation [46,XY,t(10;11)(p15;q22)]. Array CGH showed heterozygosity for a deletion of â¼3.46 Mb at 10p15.3p15.2 and gain of â¼32.21 Mb at 11q22.2q25. The patient, a 19-year-old woman, has a multiple congenital anomaly syndrome with severe developmental and growth delay, muscular hypotonia, iris coloboma, abnormal external ears, widely spaced nipples, atrial septum defect, clubfoot, and arthrogryposis multiplex congenita. Despite multiple health problems and numerous hospitalizations due to massive seizures, pulmonary insufficiency and recurrent infections the patient reached adulthood. The clinical features in our patient are compared to other cases reported in the literature of either partial monosomy 10p or partial trisomy 11q. To the best of our knowledge, this is the first report of the combination of partial trisomy 11q and partial monosomy 10p. Comparing the molecular karyotype and the phenotype of our patient to other patients, the clinical features of our patient are more likely due to partial trisomy 11q than to partial monosomy 10p.
Subject(s)
Chromosome Disorders/complications , Chromosome Disorders/genetics , Genotype , Phenotype , Trisomy/genetics , Abnormal Karyotype , Adult , Chromosome Deletion , Chromosome Disorders/diagnosis , Chromosomes, Human, Pair 10/genetics , Chromosomes, Human, Pair 11/genetics , Comparative Genomic Hybridization , Facies , Female , Humans , Trisomy/diagnosis , Young AdultABSTRACT
Neurological complications of diabetic ketoacidosis (DKA) are still associated with significant mortality and morbidity. We report on two children who suffered from acute cerebral infarction (CI) and extra pontine myelinolysis (EPM) at onset of type 1 diabetes. Initially, clinical management had not been performed according to generally accepted guidelines. Putative risk factors that may have predisposed for the development of acute cerebrovascular complications are discussed. Not only cerebral edema (CE) but also other severe neurological complications such as CI should be suspected when neurological deterioration occurs during DKA. We conclude that not only an exceeded rehydration therapy but also a rapidly reduced serum osmolality due to an unbalanced rapid blood sugar decrease and serum sodium increase may have lead to the neurological disease. We propose that a reserved and well-defined rehydration strategy in the first 6 (-12) h of therapy is crucial for recovery and can reduce neurological complications of patients with DKA.