scholarly journals Magnesium Supplement and the 15q11.2 BP1–BP2 Microdeletion (Burnside–Butler) Syndrome: A Potential Treatment?

2019 ◽  
Vol 20 (12) ◽  
pp. 2914 ◽  
Author(s):  
Merlin G. Butler
Keyword(s):  
Behavioral Problems ◽  
Clinical Severity ◽  
Brain Diseases ◽  
Medical Community ◽  
Type I ◽  
Cellular Functions ◽  
Motor Delay ◽  
Magnesium Transporters ◽  
Abnormal Brain ◽  
Paranoid Psychosis

The 15q11.2 BP1–BP2 microdeletion (Burnside–Butler) syndrome is an emerging disorder that encompasses four genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5). When disturbed, these four genes can lead to cognitive impairment, language and/or motor delay, psychiatric/behavioral problems (attention-deficit hyperactivity, autism, dyslexia, schizophrenia/paranoid psychosis), ataxia, seizures, poor coordination, congenital anomalies, and abnormal brain imaging. This microdeletion was reported as the most common cytogenetic finding when using ultra-high- resolution chromosomal microarrays in patients presenting for genetic services due to autism with or without additional clinical features. Additionally, those individuals with Prader–Willi or Angelman syndromes having the larger typical 15q11–q13 type I deletion which includes the 15q11.2 BP1–BP2 region containing the four genes, show higher clinical severity than those having the smaller 15q11–q13 deletion where these four genes are intact. Two of the four genes (i.e., NIPA1 and NIPA2) are expressed in the brain and encode magnesium transporters. Magnesium is required in over 300 enzyme systems that are critical for multiple cellular functions, energy expenditure, protein synthesis, DNA transcription, and muscle and nerve function. Low levels of magnesium are found in those with seizures, depression, and acute or chronic brain diseases. Anecdotally, parents have administered magnesium supplements to their children with the 15q11.2 BP1–BP2 microdeletion and have observed improvement in behavior and clinical presentation. These observations require more attention from the medical community and should include controlled studies to determine if magnesium supplements could be a treatment option for this microdeletion syndrome and also for a subset of individuals with Prader–Willi and Angelman syndromes.

Stridor as one of the symptoms of 5p deletion syndrome in a five-month-old child

2017 ◽  
Vol 6 (3) ◽  
pp. 37-42
Author(s):  
Katarzyna Malicka ◽  
Ewa Grochowska-Bohatyrewicz ◽  
Aleksandra Pietrzyk ◽  
Stecewicz Iwona ◽  
Ewa Jaworowska ◽  
...  
Keyword(s):  
Behavioral Problems ◽  
Genetic Disorder ◽  
Later Life ◽  
Deletion Syndrome ◽  
Type I ◽  
Speech Impairment ◽  
Motor Delay ◽  
Feeding Difficulties ◽  
Dysmorphic Features ◽  
5P Deletion

The 5p deletion syndrome (5p-, Cri-du-chat syndrome, CdCS) is a genetic disorder which results from a partial deletion of the short arm of chromosome 5. It was first described by Lejeune et al. in 1963. The incidence ranges from 1:15 000 to 1:50 000 live births. The 5p- is usually diagnosed in the first days of life because of the characteristic monotonous high pitched cat-like cry and relatively constant dysmorphic features. Other symptoms often present in the neonatal period include low birth weight, muscle hypotonia, asphyxia and feeding difficulties due to impaired suction and swallowing, which may all lead to failure to thrive. Organ malformations, with various larynx abnormalities, although not very frequent, can also be present. Symptoms that are prevalent in later life include severe motor delay and intellectual disability with significant speech impairment, as well as behavioral problems. The case report presents a female infant in her 5th month of life in whom, despite the typical symptoms of 5p-, stridor and episodes of choking were the main problems. Laryngotracheal endoscopy revealed the type I laryngeal cleft. Genetic analysis confirmed the diagnose of 5p- syndrome. The presented case shows that it is critically important to perform a further investigation and refer a child with laryngological problems coexisting with dysmorphic features to a clinical geneticist.

Stridor as one of the symptoms of 5p deletion syndrome in a five-month-old child

2017 ◽  
Vol 6 (3) ◽  
pp. 16-21
Author(s):  
Przemysław Hubert Krawczyk ◽  
Dariusz Kaczmarczyk
Keyword(s):  
Behavioral Problems ◽  
Genetic Disorder ◽  
Later Life ◽  
Deletion Syndrome ◽  
Type I ◽  
Speech Impairment ◽  
Motor Delay ◽  
Feeding Difficulties ◽  
Dysmorphic Features ◽  
5P Deletion

The 5p deletion syndrome (5p-, Cri-du-chat syndrome, CdCS) is a genetic disorder which results from a partial deletion of the short arm of chromosome 5. It was first described by Lejeune et al. in 1963. The incidence ranges from 1:15 000 to 1:50 000 live births. The 5p- is usually diagnosed in the first days of life because of the characteristic monotonous high pitched cat-like cry and relatively constant dysmorphic features. Other symptoms often present in the neonatal period include low birth weight, muscle hypotonia, asphyxia and feeding difficulties due to impaired suction and swallowing, which may all lead to failure to thrive. Organ malformations, with various larynx abnormalities, although not very frequent, can also be present. Symptoms that are prevalent in later life include severe motor delay and intellectual disability with significant speech impairment, as well as behavioral problems. The case report presents a female infant in her 5th month of life in whom, despite the typical symptoms of 5p-, stridor and episodes of choking were the main problems. Laryngotracheal endoscopy revealed the type I laryngeal cleft. Genetic analysis confirmed the diagnose of 5p- syndrome. The presented case shows that it is critically important to perform a further investigation and refer a child with laryngological problems coexisting with dysmorphic features to a clinical geneticist.

scholarly journals Targeting the CCL2-CCR2 axis in depressive disorders

2021 ◽  
Author(s):  
Katarzyna Curzytek ◽  
Monika Leśkiewicz
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Affective Disorders ◽  
Depressive Disorders ◽  
Brain Diseases ◽  
Receptor System ◽  
Proinflammatory Mediators ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Abnormal Brain

AbstractSince affective disorders are considered to be underlain by the immune system malfunction, an important role in their pathophysiology is assigned to the proinflammatory mediators. Recently, chemokines, the group of chemotactic cytokines, have become a focus for basic and clinical scientists in the context of the development and treatment of brain diseases. Among them, chemokine CCL2 and its main receptor CCR2 have become candidate mediators of abnormal brain-immune system dialogue in depression. Besides the chemotactic activity, the CCL2-CCR2 axis is involved in various neurobiological processes, neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, as well as neuroregeneration. Given the range of immunomodulatory possibilities that the CCL2-CCR2 pair can exert on the nervous system, its proinflammatory properties were initially thought to be a major contributor to the development of depressive disorders. However, further research suggests that the malfunctions of the nervous system are rather associated with impaired homeostatic properties manifested by the CCL2-CCR2 dyad dysfunctions. This review aims to present literature data on the action of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions, as well as the contribution of this ligand-receptor system to the processes underlying affective disorders. Additionally, this article draws attention to the importance of the CCL2-CRR2 pathway as a potential pharmacological target with antidepressant potential.

Insulin-dependent Diabetes Mellitus

1994 ◽  
Vol 15 (4) ◽  
pp. 137-148
Author(s):  
Leslie Plotnick
Keyword(s):  
Diabetes Mellitus ◽  
Children And Adolescents ◽  
Plasma Glucose ◽  
Behavioral Problems ◽  
Insulin Dependent Diabetes Mellitus ◽  
Health Care Team ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Type I ◽  
Insulin Dependent

Insulin-dependent diabetes mellitus (IDDM) is a chronic, serious disease in children and adolescents. Its diagnosis is straightforward and rarely subtle. The major challenges of this disease for the child, family, and health-care team involve long-term management of medical and metabolic factors as well as psychological and behavioral concerns. While developments in the past 10 to 15 years have made metabolic control technically possible, psychological stresses and behavioral problems often interfere with metabolic goals. There are few, if any, other diseases that require such intensive and extensive self-care skills. Definitions Diabetes generally is classified in two types. Type I, or IDDM, is seen mostly in younger people (children and adolescents). It previously was called juvenile onset or ketosisprone. Insulin deficiency characterizes IDDM, and patients need exogenous insulin for survival. Type II, or non-IDDM (NIDDM), previously called adult or maturity onset, is the type seen most commonly in older people and in obesity and is not discussed in this review. To make a diagnosis of diabetes, a child must have either classic symptoms with a random plasma glucose above 200 mg/dL or specific plasma glucose levels before and after a standard glucose load if asymptomatic. The diagnosis of IDDM usually is clear-cut.

Advanced oxidation protein products in serum of patients with myotonic disease type I: association with serum γ-glutamyltransferase and disease severity

2005 ◽  
Vol 43 (7) ◽  
Author(s):  
Gabriele Siciliano ◽  
Livia Pasquali ◽  
Anna Rocchi ◽  
Michela Falorni ◽  
Fabio Galluzzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Characteristic Curve ◽  
Advanced Oxidation ◽  
Clinical Severity ◽  
Total Serum ◽  
Type I ◽  
Advanced Oxidation Protein Products ◽  
Severity Scores

AbstractSteinert's disease (myotonic dystrophy type 1; MD) is caused by a CTG trinucleotide expansion on 19q13.3. Although the pathogenic mechanism underlying multisystem involvement in MD is still unclear, a role of oxidative stress in this disease has been suggested. We investigated 39 MD patients to assess the plasma concentration of advanced oxidation protein products (AOPPs) and γ-glutamyltransferase (GGT) and related them to clinical severity scores. Plasma AOPP levels (p=0.021), total serum GGT activity (p=0.0005) and GGT activity associated with low-density lipoprotein (p=0.0021) were significantly higher in patients than in controls. There was significant correlation between serum GGT levels and AOPPs (r=0.5831; p=0.0022). A statistically significant increase in serum GGT with age was found in MD patients (p=0.0193). Receiver operating characteristic curve analysis showed that higher AOPP levels were significantly associated with extra-muscular signs of the disease, i.e., cataracts and heart involvement (area under the curve±SE=0.908±0.083), but not with muscular involvement. The concomitant increment in GGT and AOPPs indicates a possible role of oxidative stress in the pathogenesis of MD type 1, while the association of increased AOPP levels with extra-muscular signs of the disease suggests that individual susceptibility to oxidative stress can modulate the extra-muscular phenotype of the disease.

Smith-Lemli-Opitz Syndrome

2016 ◽  
Author(s):  
Christopher Cunniff ◽  
Raoul C. Hennekam
Keyword(s):  
Behavioral Problems ◽  
Postnatal Growth ◽  
Clinical Severity ◽  
Metabolic Disturbances ◽  
Physical Problems ◽  
Associated Malformations ◽  
Opitz Syndrome ◽  
Cholesterol Supplementation ◽  
Sun Sensitivity ◽  
And Behavior

Smith-Lemli-Opitz syndrome (SLOS) is characterized by prenatal and postnatal growth retardation, characteristic face, genital and distal limb anomalies, and intellectual disability. There is a weak correlation between the metabolic disturbances with clinical severity and with genotype, but wide ranges exist within each group. SLOS is infrequently described in adults. The associated malformations are usually treated in infancy and childhood and have only limited influences in adulthood. Main physical problems are scoliosis and pectus formation, sun sensitivity, and disturbed hearing and vision. Rarely adrenal insufficiency is present. Marked cognitive impairment and behavioral problems including self-harm and aggressive outbursts may have a significant impact on quality of life. Cholesterol supplementation decreases sun sensitivity, but cognition and behavior seem to respond less well.

scholarly journals Exchangeable Chaperone Modules Contribute to Specification of Type I and Type II Hsp40 Cellular Function

2004 ◽  
Vol 15 (2) ◽  
pp. 761-773 ◽  
Author(s):  
Chun-Yang Fan ◽  
Soojin Lee ◽  
Hong-Yu Ren ◽  
Douglas M. Cyr
Keyword(s):  
In Vivo Studies ◽  
Cell Physiology ◽  
Type I ◽  
Type Ii ◽  
Cellular Functions ◽  
Chaperone Function ◽  
Sequence Identity ◽  
Carboxyl Terminal ◽  
High Degree

Hsp40 family members regulate Hsp70s ability to bind nonnative polypeptides and thereby play an essential role in cell physiology. Type I and type II Hsp40s, such as yeast Ydj1 and Sis1, form chaperone pairs with cytosolic Hsp70 Ssa1 that fold proteins with different efficiencies and carry out specific cellular functions. The mechanism by which Ydj1 and Sis1 specify Hsp70 functions is not clear. Ydj1 and Sis1 share a high degree of sequence identity in their amino and carboxyl terminal ends, but each contains a structurally unique and centrally located protein module that is implicated in chaperone function. To test whether the chaperone modules of Ydj1 and Sis1 function in the specification of Hsp70 action, we constructed a set of chimeric Hsp40s in which the chaperone domains of Ydj1 and Sis1 were swapped to form YSY and SYS. Purified SYS and YSY exhibited protein-folding activity and substrate specificity that mimicked that of Ydj1 and Sis1, respectively. In in vivo studies, YSY exhibited a gain of function and, unlike Ydj1, could complement the lethal phenotype of sis1Δ and facilitate maintenance of the prion [RNQ+]. Ydj1 and Sis1 contain exchangeable chaperone modules that assist in specification of Hsp70 function.

scholarly journals Short-term complication rate following orthopedic surgery in a tertiary care center in Argentina

SICOT-J ◽  
2018 ◽  
Vol 4 ◽  
pp. 26 ◽  
Author(s):  
Gaston Camino Willhuber ◽  
Joaquin Stagnaro ◽  
Matias Petracchi ◽  
Agustin Donndorff ◽  
Daniel Godoy Monzon ◽  
...  
Keyword(s):  
Orthopedic Surgery ◽  
Complication Rate ◽  
Care Center ◽  
Critical Role ◽  
Tertiary Care ◽  
Additional Treatment ◽  
Clinical Severity ◽  
Type I ◽  
Short Term ◽  
Start Time

Introduction: Registration of adverse events following orthopedic surgery has a critical role in patient safety and has received increasing attention. The purpose of this study was to determine the prevalence and severity of postoperative complications in the department of orthopedic unit in a tertiary hospital. Methods: A retrospective review from the postoperative complication registry of a cohort of consecutive patients operated in the department of orthopedic surgery from May 2015 to June 2016 was performed. Short-term complications (3 months after surgery), age gender, types of surgery (elective, scheduled urgency, non-scheduled urgency, and emergency), operative time, surgical start time (morning, afternoon or evening), American Society of Anesthesiologists score and surgeon's experience were assessed. Complications were classified based on their severity according to Dindo-Clavien system: Grade I complications do not require alterations in the postoperative course or additional treatment; Grade II complications require pharmacological treatment; Grade III require surgical, endoscopic, or radiological interventions without (IIIa) or with (IIIb) general anesthesia; Grade IV are life-threatening with single (IVa) or multi-organ (IVb) dysfunction(s), and require ICU management; and Grade V result in death of the patient. Complications were further classified in minor (Dindo I, II, IIIa) and major (Dindo IIIb, IVa, IVb and V), according to clinical severity. Results: 1960 surgeries were performed. The overall 90-day complication rate was 12.7% (249/1960). Twenty-three complications (9.2 %) were type I, 159 (63.8%) type II, 9 (3.6%) type IIIa, 42 (16.8%) type IIIb, 7 (2.8%) type IVa and 9 (3.6%) were grade V according to Dindo-Clavien classification (DCC). The most frequent complication was anemia that required blood transfusion (27%) followed by wound infection (15.6%) and urinary tract infection (6%). Discussion: The overall complication rate after orthopedic surgery in our department was 12.7%. The implementation of the DCC following orthopedic surgery was an important tool to measure the standard of care.

2-Hydroxyglutaric Acidurias

2016 ◽  
Author(s):  
Eduard A. Struys ◽  
Marjo S. van der Knaap ◽  
Gajja S. Salomons
Keyword(s):  
Acid Metabolism ◽  
Clinical Presentation ◽  
Treatment Options ◽  
Type I ◽  
Neonatal Encephalopathy ◽  
Congenital Diseases ◽  
Motor Delay ◽  
Open Treatment ◽  
Disease Entities ◽  
Hydroxyglutaric Acid

The group of congenital diseases related to 2-hydroxyglutaric acid metabolism consists of five disease entities: D-2-hydroxyglutaric aciduria Type I (D2HGA-I), D-2-hydroxyglutaric aciduria Type II (D2HGA-II), metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA), L-2-hydroxyglutaric aciduria (L2HGA), and combined D,L-2-hydroxyglutaric aciduria (DL2HGA). Overall, the clinical presentation varies from early onset with mostly lethal neonatal encephalopathy in DL2HGA to slowly progressive mental and motor delay with white matter abnormalities, with an insidious and sometimes adult clinical presentation in L2HGA. Currently no proven treatment options are available for these diseases, although recently gained novel biochemical and genetic insights open treatment perspectives.

scholarly journals Mouse model of severe recessive RYR1-related myopathy

2019 ◽  
Vol 28 (18) ◽  
pp. 3024-3036 ◽  
Author(s):  
Stephanie Brennan ◽  
Maricela Garcia-Castañeda ◽  
Antonio Michelucci ◽  
Nesrin Sabha ◽  
Sundeep Malik ◽  
...  
Keyword(s):  
Mouse Model ◽  
Force Production ◽  
Clinical Severity ◽  
Type I ◽  
Dystrophic Muscle ◽  
Major Barrier ◽  
Muscle Disorders ◽  
Functional Studies ◽  
Protein Levels ◽  
Reduced Body

Abstract Ryanodine receptor type I (RYR1)-related myopathies (RYR1 RM) are a clinically and histopathologically heterogeneous group of conditions that represent the most common subtype of childhood onset non-dystrophic muscle disorders. There are no treatments for this severe group of diseases. A major barrier to therapy development is the lack of an animal model that mirrors the clinical severity of pediatric cases of the disease. To address this, we used CRISPR/Cas9 gene editing to generate a novel recessive mouse model of RYR1 RM. This mouse (Ryr1TM/Indel) possesses a patient-relevant point mutation (T4706M) engineered into 1 allele and a 16 base pair frameshift deletion engineered into the second allele. Ryr1TM/Indel mice exhibit an overt phenotype beginning at 14 days of age that consists of reduced body/muscle mass and myofibre hypotrophy. Ryr1TM/Indel mice become progressively inactive from that point onward and die at a median age of 42 days. Histopathological assessment shows myofibre hypotrophy, increased central nuclei and decreased triad number but no clear evidence of metabolic cores. Biochemical analysis reveals a marked decrease in RYR1 protein levels (20% of normal) as compared to only a 50% decrease in transcript. Functional studies at end stage show significantly reduced electrically evoked Ca2+ release and force production. In summary, Ryr1TM/Indel mice exhibit a post-natal lethal recessive form of RYR1 RM that pheno-copies the severe congenital clinical presentation seen in a subgroup of RYR1 RM children. Thus, Ryr1TM/Indel mice represent a powerful model for both establishing the pathomechanisms of recessive RYR1 RM and pre-clinical testing of therapies for efficacy.

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