Various Degrees Of Mental Retardation Research Articles

Hardware Psychodiagnosis of Resilience Indicators Mental Health

The article reveals the psychohygienic significance of apparatus-psychological objectification of the main indicators of mental health for each person to acquire knowledge about his own individuality and self-regulation of his own mental states. It is noted that self-control of one’s own mental functioning is necessary in the process of treatment of mental disorders and the long-term rehabilitation of patients with chronic mental illnesses, as it allows activating the awareness of the main objective parameters of one’s own mental capabilities in relation to the desired capabilities necessary for a full-fledged life. The functions of the “Hyst” device, manufactured by the Kyiv Telekom-pneumatik plant under the patent of Dr. Sergii Boltivets, are presented as a separate device and a program installed on a computer that processes the received psychodiagnostic data. In accordance with the psychodiagnostic purpose of each of the components of the apparatus complex, its use allows to conduct reactometry, labiliometry and tremormetry of the psychomotor praxis of thinking of children and adults, starting, as a rule, from the age of 5. The device provides the possibility of choosing both a single signal and a series of 10 responses with separate calculation of the reaction of the right and left hand and leg. This provides a psychodiagnostic assessment of interhemispheric interaction and the presence of asymmetry of interhemispheric functioning and its severity. The obtained data are important for identifying the consequences of unconscious but existing craniocerebral injuries and other dysfunctions of psychophysical development. The results of psychological examinations of 2,548 people, including children and adults aged 5 to 82 years, regardless of mental health status, including both self-actualized individuals with high quality indicators of mental health and individuals with chronic mental disorders and various degrees of mental retardation. This made it possible to generalize the main indicators of the instrumental and psychological objectification of the main indicators of the stability of mental health. It was established that the functional indicators of reactometry, labiliometry and tremometry are the basic characteristics of individuality, activity and the ability to self-regulate, which are the main indicators of the stability of a person’s mental health. It was noted that such universal forms and patterns of mental self-organization of a person, which, being transformed during human life, are not lost, have the greatest value.

A rare cause of hypocalcemia: Pseudohypoparathyroidism

Pseudohypoparathyroidism is a rare inherited metabolic disorder that associated with parathormone resistance. Low serum calcium, high phosphates and raised parathormone levels suggesting parathormone resistance are biochemical characteristic features of disorder . Pseudohypoparathyroidism type 1 is known as Albright’s hereditary osteodystrophy that characterized by a typical phenotype. This syndrome encompasses multiple clinical findings such as brachydactyly, rounded face, short stature, central obesity, and variable degrees of mental retardation. Here, we present a patient with pseudohypoparathyroidism which is rare cause of hypocalcemia and parathormone resistance .

Clinical features and genetic analysis of three children with mental retardation, language impairment and autistic features due to de novo variants of FOXP1 gene

To analyze the clinical features and genetic basis of three children with mental retardation, language impairment and autistic features due to de novo variants of FOXP1 gene. Clinical data of the children were collected.Trio-whole exome sequencing was carried out for the children and their parents. Pathogenicity of the variants was analyzed through bioinformatics prediction. All of the children had various degrees of mental retardation in conjunct with language deficit, global developmental delay, abnormal behavior and peculiar facial features, among whom two also developed autism spectrum disorders. The results of genetic testing showed that all three children harbored de novo variants of the FOXP1 gene, namely c.613_c.614delCTinsTA, c.1248delC and c.1393A>G. Two of these were frameshift variants and one was missense variant, which were all rated as pathogenic based on the guidelines of the American College of Medical Genetics (ACMG). Database search suggested that c.613_c.614delCTinsTA and c.1248delC were unreported previously. For the three children from unrelated families with mental retardation in conjunct with language deficit, global growth delay, abnormal behavior and peculiar facial features, the c.613_ c. 614delCTinsTA, c.1248delC and c.1393A>G variants of the FOXP1 gene may be the pathogenic factors. Above cases have further expanded the genotype-phenotype profile of FOXP1 deficiency syndrome.

Pseudohypoparathyroidism and its various phenotypes: three sisters with three different clinical presentations

Pseudohypoparathyroidism (PHP) is a heterogeneous group of hereditary disorders characterized by clinical and biological characteristics of resistance to parathyroid hormone (PTH) caused by impaired hormonal signalling via receptors that are coupled, through the α- subunit of the stimulatory G protein (Gsα). In some cases, resistance to other hormones (such as TSH, gonadotropins, GHRH and calcitonin) that have receptors coupled via Gsα is observed. A subset of patients with PHP are characterized by the variable expression of a collection of physical features, termed Albright hereditary osteodystrophy (AHO), which includes brachydactyly, rounded face, short stature, central obesity, subcutaneous ossifications, and variable degrees of mental retardation. These patients face a wide range of problems from early childhood to adulthood, which include potentially severe alterations in mineral metabolism, which could be associated with seizures; other endocrine deficiencies due to hormone resistance that lead to hypothyroidism, hypogonadism and GH deficiency; growth impairment independently of hormonal status; ectopic ossifications with potential severe limitation of mobility; skeletal issues and cognitive and psychomotor impairment. Here we report three sisters affected by pseudohypoparathyroidism but with remarkably differences from each other in terms of phenotypic and clinical-auxological characteristics, a demonstration of how this disease is characterized by a very heterogeneous phenotype, even among patients carrying the same genetic alteration.

Badania obiektywne słuchu u osób z zespołem Downa a dalsze postępowanie logopedyczne

Down syndrome (ZD) is the most common pathology of the human genotype. In the speech therapy practice, we very often meet children with DS. Children with DS struggle with many health problems, incl. visual impairment, decreased muscle tone, heart defects and hearing impairment. Due to various degrees of mental retardation, it is important to eliminate factors that additionally adversely affect linguistic, cognitive and social development. Hearing disorders are very common in this group of patients. As a result of such factors as an abnormal anatomy of the hearing organ, lowered immunity, frequent inflammation of the upper respiratory tract and reduced muscle tone, the chronic ear inflammation occurs. Consequently, this may lead to hearing loss. The aim of the study is to assess the usefulness of objective hearing tests in children with DS in relation to the proposedspeech therapy.Material: The material of the study included 39 people with Down’s syndrome (ZD group), aged 1 to 27 (mean 10.7 ± 5.2), including 19 boys and 20 girls, and 112 people (58 girls and 63 boys) with normal hearing (age from 1 to 35 years, mean age (mean: 9.8 ± 5.7 years), who constituted the control group - Group N.Results: Based on the analysis of the results of all objective hearing tests performed in all ears (n = 78), the following diagnoses were made: auditory norm 36 ears (46.1%), cochlear hearing loss 27 ears (34.6%), conductive hearing loss 8 ears (10, 3%), deafness in 7 ears (9.0%). Conclusions: The results of this study entitle us to draw a conclusion that objective tests must be performed before starting speech therapy, also (and perhaps in particular) in patients with Down’s syndrome. Clinical practice shows that quite often in patients undergoing speech therapy it is the speech therapist who forces the child to be referred for a full diagnosis of the hearing organ using objective methods. The results of this study showed the high value of objective hearing tests in thediagnosis of hearing disorders in people with Down syndrome, regardless of the patient’s age.

Probably Pathogenic KMT2D Variants Presenting with Cytopenias and Primary Immune Deficiency

Background The mutations in KMT2D gene are well known to be associated with Kabuki syndrome. Up to date, 1,027 different germline KMT2D variants have been reported in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/?term=KMT2D%5Bgene%5D), and among them, 365 variants (35.5%) are classified as uncertain significance and 53 (5.2%) are assigned to conflicting interpretations. This means about 40% of KMTD2 variants still need further evaluation to figure out whether they are 'pathogenic' or 'likely pathogenic'. Currently, the problem with the respect to the interpretation of variants is that they are prone to be reported as variants of unknown significance (VUS) without further study if the KMT2D variants have not been clinically described and reported previously. And in the clinical field, the KMT2D variants interpreted as VUS most likely do not get paid attention by the clinicians and can be easily ignored without further testing. Recently, Hadjadj et al.1 brought up the criteria 'probably pathogenic' variants which include the minor allele frequency less than 0.01 in the general population, and in Silico algorithms predicts the pathogenicity of missense variants. The authors found these 'probably pathogenic' variants were not significantly different from 'pathogenic' mutations in Evans syndrome in terms of clinical manifestations. Hypothesis and objective We hypothesized that there could be 'probably pathogenic' KMT2D variants which have been reported as VUS in patients with hematologic cytopenias and primary immune deficiency and we sought to find these 'probably pathogenic' variants for further evaluation to figure out their pathogenicity. Methods We analyzed the next generation sequencing data performed on patients with hematologic cytopenias and primary immune deficiency at the Ann and Robert H. Lurie Children's Hospital from March 2017 to May 2019. This primary immune deficiency (PID) panel analyzes 290 genes and the clinical manifestations of the patients were compared with the previous reports published regarding the KMT2D pathogenic mutations. We reviewed not only the online PubMed resource, but the websites well known for gene analysis were also used as references (https://www.ncbi.nlm.nih.gov/clinvar/, http://exac.broadinstitute.org/, http://genetics.bwh.harvard.edu/pph2/, http://provean.jcvi.org/index.php, https://sift.bii.a-star.edu.sg/, etc). Results Among 52 patients who had a PID panel ordered, 10 patients (19.2%) were found to have KMT2D variants. Among them, 4 variants (7.6%) were polymorphisms (c.7705G>A, p.Gly2569Ser; c.11849A>G, p.Gln3950Arg; c.1408C>T, p.Pro470Ser; c.2506C>A, p.Ile238Val) and 6 (11.5%) 'probably pathogenic' KMT2D variants were newly identified. Novel heterozygous KMT2D variants, previously reported as VUS: c.15341A>C, p.His5114Pro; c.10640G>A, p.Arg3547; c.6902C>T, p.Pro2301Leu; c.7328G>T, p.Arg2443Leu; c.15694A>G, p.I5232V; c.7001G>A, p.R2334Q were identified in patients who presented with various clinical manifestations known to be associated with KMT2D mutations which are neutropenia, anemia, thrombocytopenia, cardiac anomaly, urogenital anomaly, primary immune deficiency, variable degrees of mental retardation and distinctive facial features that include arched eyebrows, long eyelashes, elongated eyelids with lower lids that turn out, prominent ears, a flat tip of the nose, and a downward slant to the mouth. Further parental testing revealed one of them was a novel de novo mutation which was reclassified as 'likely pathogenic', 4 variants were inherited from mother or father and parental testing was not done for 1 patient. Conclusion We concluded that the mutational gene analysis should be correlated with patients' clinical manifestations. The second look analysis of the 'probably pathogenic' variants reported as VUS to figure out the clinical meaning would be important in terms of diagnosis and treatment of patients in the future. Further evaluation regarding family history and gene analysis would be necessary as well as further downstream pathway studies to confirm the pathogenicity of the 'probably pathogenic' KMT2D variants.

Aminoguanidine alleviated MMA-induced impairment of cognitive ability in rats by downregulating oxidative stress and inflammatory reaction

Methylmalonic acidemia (MMA) is the most common organic acidemia in childhood. Many “treated” patients continued to display various degrees of mental retardation and psychomotor delay, which could be caused by brain damage from elevated oxidative stress. Aminoguanidine (AG), a synthetic antioxidant, was tested in a MMA rat model for its potential therapeutic effects on memory impairment. The effects of AG on MMA-induced cognitive impairment in Wistar rats were evaluated with Morris Water Maze. The levels of nerve cell apoptosis and microglial activation were investigated to illustrate the mechanisms of the improvement of cognition with AG treatment in MMA rats. To further explore the mechanism of neuroprotection induced by AG, several biomarkers including free radicals and inflammatory cytokines in the hippocampus were quantified. The results showed that the rats treated with AG exhibited better neurological behavior performances than MMA model rats. The AG-treated rats had a decreased level of apoptosis of the hippocampal neurons, which could be the structural basis of the observed neural behavior protection. In addition, AG treatment significantly inhibited the activation of microglia. The AG-treated rats had decreased levels of IL-1β, IL-6, TNF-α, NO, malonaldehyde and iNOS activities in the hippocampus. The level of glutathione and superoxide dismutase activity in the hippocampus of the AG-treated rats increased significantly. In conclusion, AG could alleviate the MMA-induced cognitive impairment via down-regulating of oxidative stress and inflammatory reaction and provide a basis as a therapeutic potential against MMA-induced cognitive impairment.

MORPHOFUNCTIONAL AND PSYCHOPHYSIOLOGICAL FEATURES IN CHILDREN WITH INTELLECTUAL DISORDERS

The article studies morphofunctional and psychophysiological features in children with mental disabilities. The research features 7–9-year-old children, both male and female, with different central nervous system diseases (various degrees of mental retardation, Down's syndrome, autism, epilepsy). All the children were characterized by various degrees of mental retardation. The degree of mental retardation and the type of central nervous system affect, in various ways, the severity of abnormalities in physical development, impaired posture, manual dexterity development, especially the formation of functional brain asymmetry and spatial perception. In the group of children with mild mental retardation there were fewer examples of low manual dexterity development, uncertain signs of functional asymmetry of the brain and low levels of spatial perception compared to the group of children with severe mental retardation, Down syndrome and autism.

A Rare Association of Monosomy 18 with Translocation 13p 11/18 with Cholelithiasis

Monosomy 18p is a rare chromosomal disorder in which all or part of the short arm (p) of chromosome 18 is deleted (monosomic). The disorder is typically characterized by short stature, variable degrees of mental retardation, speech delays, malformations of the skull and facial (craniofacial) region, and/or additional physical abnormalities. We report monosomy 18 with translocation 13p 11/18 with Cholelithiasis in a 8 year old girl who presented with acute right hypochondriac pain with fever. This association has never been reported in this age group. This case report highlights this rare association which a clinician should keep in mind while dealing with this disorder.

Multidisciplinary approach for evaluation of neurocutaneous disorders in children in Sohag University Hospital, Upper Egypt

BackgroundNeurocutaneous syndromes (NCS) are a broad term for a group of neurologic disorders that involve the nervous system and the skin. The most common examples are neurofibromatosis type 1 (NF-1) and type 2 (NF-2), tuberous sclerosis (TS), Sturge–Weber syndrome (SWS), ataxia telangiectasia (AT), and Von Hippel Lindau disease (VHL). These disorders are characterized clinically by neurological manifestations such as convulsions, mental retardation and learning disabilities in addition to cutaneous manifestations, and lastly tubers (benign growths found in different organs of the body). Aim of the studyThis study aimed to identify clinical, imaging, and neurophysiological profiles of neurocutaneous disorders. Children presented to the Pediatric neurology and Dermatology clinics, Sohag University Hospital who fulfilled the criteria for diagnosis of specific neurocutaneous syndromes were eligible for this study. Patients and methodsAll studied patients were subjected to thorough clinical history, full clinical examination, developmental assessment, and dermatological examination. Computed tomography of the brain (CT) and electroencephalography (EEG), ophthalmic, and phoniatric evaluation were also done for all children. Echocardiography was done for only twenty children. ResultsDuring the period of the study we diagnosed 27 cases with neurocutaneous disorders, tuberous sclerosis represented the majority of cases as it was detected in 12 cases (44.45%). The main complaint was convulsions in 19 cases (70.37%), whereas skin pigmentation was detected in 18 cases (66.66%). Developmental assessment showed that global developmental delay was found in 20 cases (74%). CT of the brain showed that 15 cases (55.55%) had intracranial calcifications and abnormal EEG findings were detected in 23 cases (85.2%). 85% of the studied children had various degrees of mental retardation. Echocardiography showed that three cases (15%) had ventricular wall tumor mostly rhabdomyoma. ConclusionNeurocutaneous disorders had multiple clinical presentations and required a team work approach including various specialties in their evaluation and management.

The characterization of neuroenergetic effects of chronic L-tyrosine administration in young rats: evidence for striatal susceptibility.

Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in hepatic cytosolic aminotransferase. Affected patients usually present a variable degree of mental retardation, which may be related to the level of plasma tyrosine. In the present study we evaluated effect of chronic administration of L-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase and complexes I, II, II-III and IV in cerebral cortex, hippocampus and striatum of rats in development. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); rats were killed 12 h after last injection. Our results demonstrated that L-tyrosine inhibited the activity of citrate synthase in the hippocampus and striatum, malate dehydrogenase activity was increased in striatum and succinate dehydrogenase, complexes I and II-III activities were inhibited in striatum. However, complex IV activity was increased in hippocampus and inhibited in striatum. By these findings, we suggest that repeated administrations of L-tyrosine cause alterations in energy metabolism, which may be similar to the acute administration in brain of infant rats. Taking together the present findings and evidence from the literature, we hypothesize that energy metabolism impairment could be considered an important pathophysiological mechanism underlying the brain damage observed in patients with tyrosinemia type II.

Brain morphological defects in prolidase deficient mice: first report.

Prolidase gene (PEPD) encodes prolidase enzyme, which is responsible for hydrolysis of dipeptides containing proline or hydroxypro-line at their C-terminal end. Mutations in PEPD gene cause, in human, prolidase deficiency (PD), a rare autosomal recessive disorder. PD patients show reduced or absent prolidase activity and a broad spectrum of phenotypic traits including various degrees of mental retardation. This is the first report correlating PD and brain damages using as a model system prolidase deficient mice, the so called dark-like (dal) mutant mice. We focused our attention on dal postnatal brain development, revealing a panel of different morphological defects in the cerebral and cerebellar cortices, such as undulations of the cerebral cortex, cell rarefaction, defects in cerebellar cortex lobulation, and blood vessels overgrowth. These anomalies might be ascribed to altered angiogenic process and loss of pial basement membrane integrity. Further studies will be directed to find a correlation between neuroarchitecture alterations and functional consequences.

Clinical and Molecular Cytogenetic Study of 38 Williams-Beuren Syndrome Tunisian Patients

Background: Williams-Beuren syndrome (WBS) is a rare multi-system genomic disorder, caused by 7q11.23 microdeletion with a prevalence of 1/7500 - 1/20,000 live births. Clinical phenotype includes typical facial dysmorphism (elfin face), mental retardation associated with a peculiar neuropsychological profile and congenital heart defects. Other signs are occasional like ocular, skeletal, renal and dental anomalies. Here in, we present 38 WBS Tunisian patients. Methods: All patients underwent a genetic consultation and in order to confirm the clinical diagnosis of WBS, fluorescent in situ hybridization (FISH) was applied on metaphase spreads using the dual color locus specific identifier WBS region probe (Vysis probe) that hybridized to the ELN and LIMK1 loci at 7q11.23 and to control loci D7S486 and D7S522 at 7q31. About 15 to 20 metaphases were analyzed for each case. Results: The mean age at diagnosis was 4 years and 4 months. All patients showed facial dysmorphism. 66% (23/35) have cardiovascular anomaly, peripheral pulmonary stenosis (10/35) is interestingly more frequent than the supravalvular aortic stenosis (7/35). Various degrees of mental retardation were present and a normal intelligence was found in three patients. The unique cognitive profile was found in all patients except one who had autistic disorders. Ocular anomalies (13/38) were less frequent than described, the skeletal anomalies too (12/38). Dental malformations were frequent (22/32). Idiopathic hypercalcemia was present in 50% of children less than one year (2/4). Conclusions: WBS was a rare disorder, cardinal signs (facial dysmorphism, mental retardation and cardiovascular defects) were found in our patients in the same proportions than described. The occasional clinical signs have proportion different of precedent reported like hypercalcemia, ocular and dental anomalies. The identification of the different clinical signs in WBS patients permits to establish a strategy of follow up.

MCT8 Deficiency

Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked disorder resulting from an impairment of the transcellular transportation of thyroid hormones. Within the central nervous system thyroid hormone transport is normally mediated by MCT8. Patients are described as affected by a static or slowly progressive clinical picture which consists of variable degrees of mental retardation, hypotonia, spasticity, ataxia and involuntary movements, occasionally paroxysmal. The authors describe the clinical and neuroradiological picture of 3 males patients with marked delayed brain myelination and in which the clinical picture was dominated by early onset nonparoxysmal extrapyramidal symptoms. In one subject a novel mutation is described.

Pyruvate and creatine prevent oxidative stress and behavioral alterations caused by phenylalanine administration into hippocampus of rats

Phenylketonuria is characterized by a variable degree of mental retardation and other neurological features whose mechanisms are not fully understood. In the present study we investigated the effect of intrahippocampal administration of phenylalanine, isolated or associated with pyruvate or creatine, on rat behavior and on oxidative stress. Sixty-day-old male Wistar rats were randomly divided into 6 groups: saline; phenylalanine; pyruvate; creatine; phenylalanine + pyruvate; phenylalanine + creatine. Phenylalanine was administered bilaterally in the hippocampus one hour before training; pyruvate, at the same doses, was administered in the hippocampus one hour before phenylalanine; creatine was administered intraperitoneally twice a day for 5 days before training; controls received saline solution at same volumes than the other substances. Parameters of exploratory behavior and of emotionality were assessed in both training and test sessions in the open field task. Rats receiving phenylalanine did not habituate to the open field along the sessions, indicating deficit of learning/memory, but parameters of emotionality were normal, not interfering in the habituation process. Pyruvate or creatine administration prevented the lack of habituation caused by phenylalanine. Pyruvate and creatine also prevented alterations provoked by phenylalanine on lipid peroxidation, total content of sulfhydryls, total radical-trapping antioxidant potential and total antioxidant reactivity. The results suggest that the behavioral alterations provoked by intra-hippocampal administration of phenylalanine may be caused, at least in part, by oxidative stress and/or energy deficit. If this also occurs in PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric patients.

The Clinical Implication of Array-CGH (Agilent 244K and 4X180K) Analysis in Pediatric Services

Background and aim: Array comparative genomic hybridisation (aCGH) is used to detect small copy number changes within the genome that are not always visible by conventional karyotyping. Patients with mental retardation (MR), developmental delay (DD), autism, or/and multiple congenital anomalies (MCA) may have normal standard karyotype and not always can be classified as distinctive syndromes. To detect submicroscopic chromosomal aberrations 253 patients with various degrees of MR, DD, autism, and/or single or multiple congenital abnormalities and normal previous conventional karyotype, many of which had also received a variety of other genetic tests (FRAX, RETT, single FISH tests or metabolic screens), were analyzed with aCGH.Methods: Agilent 244K & 4x180K was performed allowing a theoretical resolution of >50Kb.Results: Clinically significant submicroscopic imbalances were detected in 92 (∽30%) patients. Some patients presented with more than one aberration relevant to their phenotype. The high percentage of positive patients is probably due to the strict criteria of patient selection. Table Table Full size table Conclusions: Array CGH is a powerful tool for the identification of novel chromosomal syndromes and for more accurate prognosis and phenotype-genotype correlations.

Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum

Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder.

Neurological Disorders of Purine and Pyrimidine Metabolism

Purines and pyrimidines, regarded for a long time only as building blocks for nucleic acid synthesis and intermediates in the transfer of metabolic energy, gained increasing attention since genetically determined aberrations in their metabolism were associated clinically with various degrees of mental retardation and/or unexpected and often devastating neurological dysfunction. In most instances the molecular mechanisms underlying neurological symptoms remain undefined. This suggests that nucleotides and nucleosides play fundamental but still unknown roles in the development and function of several organs, in particular central nervous system. Alterations of purine and pyrimidine metabolism affecting brain function are spread along both synthesis (PRPS, ADSL, ATIC, HPRT, UMPS, dGK, TK), and breakdown pathways (5NT, ADA, PNP, GCH, DPD, DHPA, TP, UP), sometimes also involving pyridine metabolism. Explanations for the pathogenesis of disorders may include both cellular and mitochondrial damage: e.g. deficiency of the purine salvage enzymes hypoxanthine-guanine phosphoribosyltransferase and deoxyguanosine kinase are associated to the most severe pathologies, the former due to an unexplained adverse effect exerted on the development and/or differentiation of dopaminergic neurons, the latter due to impairment of mitochondrial functions. This review gathers the presently known inborn errors of purine and pyrimidine metabolism that manifest neurological syndromes, reporting and commenting on the available hypothesis on the possible link between specific enzymatic alterations and brain damage. Such connection is often not obvious, and though investigated for many years, the molecular basis of most dysfunctions of central nervous system associated to purine and pyrimidine metabolism disorders are still unexplained.

Seizures and EEG pattern in Kabuki syndrome

Purpose: Kabuki syndrome (KS) is a rare dysmorphogenic disorder that is characterized by multiple congenital abnormalities with central nervous system involvement. The diagnosis is clinical and a variable degree of mental retardation is always present. Epilepsy is frequently reported, but a typical electroclinical pattern has not been described. We describe the electroclinical features of eight KS non-Japanese patients with epilepsy. Methods: We analysed seizure characteristics and pattern EEG and clinical outcomes in eight KS patients. Results: All patients presented with focal seizures. A frontal epileptic status was present in two cases. We highlighted the fact that, during evolution, seven patients shared the same interictal EEG pattern, which was characterized by isolated or repetitive biphasic spikes or sharp waves, followed by a slow wave of medium and high voltage, predominantly localised in the fronto-central regions. The natural course of seizures is favourable. Conclusions: Our results showed a peculiar homogeneous electroclinical pattern in KS, characterized by focal seizures more frequently origin in fronto-central area which demonstrated that seizures are mostly focal in type and that a fronto-central origin is more frequently evident.

Dyggve-Melchior-Clausen syndrome: clinical, genetic, and radiological study of 15 Egyptian patients from nine unrelated families.

Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive type of skeletal dysplasia. It is characterized by the association of progressive spondyloepimetaphyseal dysplasia (SEMD), microcephaly, mental retardation (MR), and coarse facies. The radiographic appearance of generalized platyspondyly with double-humped end plates and the lace-like appearance of iliac crests are pathognomonic and distinctive of DMC syndrome. The disorder results from mutations in the DYM gene mapped in the 18q12-12.1 chromosomal region. In this report, we studied 15 Egyptian cases with DMC syndrome from nine unrelated families. We aimed to emphasize the characteristic clinical and radiological features in order to differentiate the condition from other SEMDs and mucopolysaccharidosis (MPS). Patients were subjected to detailed history taking, three-generation family pedigree analysis, complete physical examination, anthropometric measurements, quantitative estimation, and two-dimensional electrophoresis of glycosaminoglycans in the urine and measurement of α-l-iduronidase and galactose-6-sulfatase enzyme activities to exclude Hurler and Morquio diseases (MPS type I and MPS type IVA), respectively. Other investigations were carried out whenever indicated. All patients were the offspring of consanguineous apparently normal parents. Positive family history and similarly affected sibs were noted, confirming the autosomal recessive inheritance pattern of the syndrome. Short stature, microcephaly, variable degree of MR, and coarse facies were constant features. The frequency of characteristic orthopedic and radiological findings was reported. Orthopedic surgical intervention was carried out for two patients. The study concluded that DMC syndrome may be more frequent in Egypt than previously thought, especially due to misdiagnosis. Characteristic facial dysmorphism, body habitus, and pathognomonic radiological signs suggest the diagnosis and differentiate it from other types of SEMDs and MPS for proper genetic counseling and management.