Cases of inborn errors of metabolism diagnosed in children with autism
CAKAR Emel Nafiye1, YILMAZBAS Pınar2
JANUARY 30, 2021
Clinical Neuroscience - 2021;74(01-02)
CAKAR Emel Nafiye1, YILMAZBAS Pınar2
JANUARY 30, 2021
Clinical Neuroscience - 2021;74(01-02)
Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.
Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of patient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.
Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.
Over the second half of the 19th century, numerous theories arose concerning mechanisms involved in understanding of action, imitative learning, language development and theory of mind. These explorations gained new momentum with the discovery of the so called “mirror neurons”. Rizzolatti’s work inspired large groups of scientists seeking explanation in a new and hitherto unexplored area of how we perceive and understand the actions and intentions of others, how we learn through imitation to help our own survival, and what mechanisms have helped us to develop a unique human trait, language. Numerous studies have addressed these questions over the years, gathering information about mirror neurons themselves, their subtypes, the different brain areas involved in the mirror neuron system, their role in the above mentioned mechanisms, and the varying consequences of their dysfunction in human life. In this short review, we summarize the most important theories and discoveries that argue for the existence of the mirror neuron system, and its essential function in normal human life or some pathological conditions.
Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.
Transcranial magnetic stimulation is a non-invasive procedure that uses robust magnetic fields to create an electrical current in the cerebral cortex. Dual stimulation consists of administering subthreshold conditioning stimulation (CS), then suprathreshold test stimulation (TS). When the interstimulus interval (ISI) is 1-6 msec, the motor evoked potential (MEP) decreases in amplitude; this decrease is termed “short interval intracortical inhibition” (SICI); when the ISI is 7-30 msec, an increase in MEP amplitude occurs, termed “short interval intracortical facilitation” (SICF). Continuous theta burst stimulation (cTBS), often applied at a frequency of 50 Hz, has been shown to decrease cortical excitability. The primary objective is to determine which duration of cTBS achieves better inhibition or excitation. The secondary objective is to compare 50 Hz cTBS to 30 Hz and 100 Hz cTBS. The resting motor threshold (rMT), MEP, SICI, and SICF were studied in 30 healthy volunteers. CS and TS were administered at 80%-120% and 70%-140% of rMT at 2 and 3-millisecond (msec) intervals for SICI, and 10- and 12-msec intervals for SICF. Ten individuals in each group received 30, 50, or 100 Hz, followed by administration of rMT, MT-MEP, SICI, SICF immediately and at 30 minutes. Greater inhibition was achieved with 3 msec than 2 msec in SICI, whereas better facilitation occurred at 12 msec than 10 msec in SICF. At 30 Hz, cTBS augmented inhibition and suppressed facilitation, while 50 Hz yielded less inhibition and greater inter-individual variability. At 100 Hz, cTBS provided slight facilitation in MEP amplitudes with less interindividual variability. SICI and SICF did not differ significantly between 50 Hz and 100 Hz cTBS. Our results suggest that performing SICI and SICF for 3 and 12 msec, respectively, and CS and TS at 80%-120% of rMT, demonstrate safer inhibition and facilitation. Recently, TBS has been used in the treatment of various neurological diseases, and we recommend preferentially 30 Hz over 50 Hz cTBS for better inhibition with greater safety and less inter-individual variability.
Hypertension and nephrology
[Cardiovascular drugs are used for the treatment and primary and secondary prevention of diseases affecting the cardiovascular system. Like all drugs, these drugs may have pharmacological effects in addition to their therapeutic effects. Of particular importance are the effects that affect, have a positive or negative effect on global or cardiac metabolism. In addition to primary cardiovascular diseases, most cardiovascular diseases are strongly influenced by patient’s metabolic status and adaptation to the disease itself. Drugs that affect global and cardiovascular metabolism, in addition to their recognized main mechanism of action, may be of particular interest, both because of their potential beneficial and detrimental effects, especially in the long run, as these drugs are most likely to be taken by our patients for the rest of their lives. These effects should be known to physicians treating patients with cardiovascular disease, and their therapeutic decisions should be made by this knowledge. This article is intended to assist in this decision making by reviewing the metabolic effects of major cardiovascular drugs.]
Lege Artis Medicinae
[The complex energy balance includes maintenance of both normal body mass and body temperature. In the homeostasis regulation it is important that the activities of several physiologic processes are balanced with each other, for example, the balance between food intake and energy expenditure is crucial to maintain normal body mass, while the balance between heat production and heat loss is vital in determining body temperature. Obesity and loss of body weight, as well as fever and hypothermia are consequences of the dysregulation in energy balance. In our research, we studied receptorial and neurohumoral mechanisms involved in the maintenance and in the impairment of energy balance. This paper gives an overview of our most important findings, which served as the basis of the application submitted to and awarded with 3rd prize by the Prof. Dr. Laszlo Romics Memorial Foundation. We review the physiologic role of transient receptor potential channels, mostly of vanilloid-1 (formerly: capsaicin receptor) in the regulation of body temperature and body mass. Among the neuropeptides which take part in the maintenance of energy balance, we present the thermoregulatory effects of alpha-melanocyte stimulating hormone and pituitary adenylate cyclase-activating polypeptide. Last, among the molecular mechanisms of systemic inflammation, which is characterized by thermoregulation disorders (e.g., fever, hypothermia), we recap the role of the vanilloid-1 and neurokinin-1 receptor, and bilirubin.]
Hypertension and nephrology
[Summary in the antihypertensive therapy, in addition to the RAS-blockers (ACE-inhibitors or ARBs), calcium antagonists and thizid-like diuretics, other antihypertensive drugs with different mechanisms of actions, such as the imidazoline I1 receptor agonists, are beneficially used. Several international and Hungarian studies showed the results of the effects of these agents. Authors emphasize the effects of the VERITAS study showing that in hypertensive patients the imidazoline I1 receptor agonist, rilmenidine significantly decreased the office blood pressure as well as the blood pressure measured by ambulatory blood pressure monitoring (ABPM). The white-coat reaction and left ventricular hypertrophy (LVH) were also decreased. In a separate study involving hypertensive subjects rilmenidine significantly increased baroreflex sensitivity. This effect may contribute - mainly during daytime - to the antihypertensive effect. Authors summarise the most important actions of rilmenidine, and the selected publications on the results of the Hungarian and international investigations.]
[It is now evident that cancer hypoxia is one of the new hallmark of cancer due to its consequences in gene expression, metabolism and biology. The importance of cancer hypoxia was recognized by the Nobel-price award in 2019. There are three major causes of cancer hypoxia: insuffi cient vascularization, systemic hypoxia of the host and constitutive activation of oncogene driven signaling pathways, all leading to a unique form of genetic reprogramming by HIF transcription factors. The consequences of HIF activation in cancer is the angiogenic phenotype, a new metabolic profi le and an immunsuppressive microenvironment. Furthermore, cancer hypoxia and the cellular adaptation lead to therapy resistance. Accordingly there is an urgent need to develop target therapies of hypoxia to improve effi cacies of various therapeutic modalities.]
[INTRODUCTION - All forms of diabetes are associated with increased fracture risk. In type 2 diabetes, bone mineral density is increased. In order to determine whether increased bone density is a consequence of diabetes-related metabolic changes or rather a primary alteration independent of these changes, we examined women and men with the following characteristics: normal glucose tolerance; genetically determined risk of T2DM but healthy on the basis of detailed metabolic tests; or incipient glucose intolerance, praediabetic state. PATIENTS AND METHODS - We included 72 men with normal glucose tolerance; seven men with normal glucose tolerance and first-degree relative(s) with diabetes; 64 body fat mass adjusted and BMI-adjusted men with glucose intolerance; 36 healthy women with normal glucose tolerance; 12 women with normal glucose tolerance and first-degree relative(s) with T2DM and 88 women with glucose intolerance. Muscle glucose uptake was measured by hyperinsulinaemic-normoglycaemic clamp, and bone density was measured by DEXA. RESULTS - In healthy men, the connection between leptin and BMDL1-4 is positive and the relationship between testosterone and BMDL1-4 is negative, but both correlations disappear in the early praediabetic stage. In the whole female study population, negative correlations were found between total BMD and adiponectin (r=-0.318, p<0.0001), and osteocalcin (r=-0.412, p<0.0000), which stayed significant after adjustments for body fat percent and age in case of impaired glucose tolerance. CONCLUSION - In women with healthy glucose metabolism who have first-degree relative(s) with diabetes, increased bone density is not related to changes in glucose metabolism. Our study emphasizes the substantial gender differences in the relationship between density of the femur and vertebrae and metabolism. Our data question the mediatory role of adiponectin shown in animal studies in the insulin-sensitizing, glucose metabolism improving effect of osteocalcin in men.]
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