Inherited Disorders of Brain Neurotransmitters: Pathogenesis and Diagnostic Approach

2014 ◽  
pp. 1-8
Author(s):  
Krystyna Szymańska ◽  
Katarzyna Kuśmierska ◽  
Urszula Demkow
Keyword(s):  
Diagnostic Approach ◽  
Inherited Disorders ◽  
Brain Neurotransmitters

Structure, compositon and function of the dermal-epidermal junction: Relevance in cutaneous disease and diagnosis

1989 ◽  
Vol 47 ◽  
pp. 868-869
Author(s):  
K. A. Holbrook
Keyword(s):  
Basement Membrane ◽  
Epidermolysis Bullosa ◽  
Normal Skin ◽  
Lamina Densa ◽  
Inherited Disorders ◽  
Ultrastructural Studies ◽  
Type Iv ◽  
Type Vii Collagen ◽  
Attachment Structures ◽  
Matrix Components

The dermal-epidermal junction (DEJ), or basement membrane rone, is the boundary between the epithelial and mesenchymal compartments of the skin; epidermal and fibroblastic cells in these two regions collaborate to synthesire its components. Ultrastructural studies (TEM and SEM) have defined a series of planes or layers (basal epidermal, lamina lucida, lamina densa, sublamina densa) and the morphology and density of attachment structures (hemidesmosomes, anchoring filaments, anchoring fibrils and anchoring plaques) in this region of normal skin. Change in structure of the DEJ provides information about the history of the tissue; reduplication of the lamina densa, for example, indicates a site of cell detachment or migration, or remodelling that accompanies repair of focal damage. In normal skin the structure of the DEJ is stable; in pathologic conditions it can be compromised by the congenital absence of certain structures or antigens (e.g., in the inherited disorders, epidermolysis bullosa [EB]) or by enzymatic degradation (e.g., in tumor invasion). Dissolution of the DEJ can also occur normally during the formation of epidermal appendages (e.g., hair follicles) and as melanocytes and Langerhans cells migrate into the epidermis during development.Biochemical and immunohisto/cytochemical studies have identified more than 20 molecules at the DEJ. These include well known matrix molecules (e.g., types IV and V collagen, laminin and fibronectin) and skin-specific antigens. The latter have been identified by autoantibodies or specific polyclonal or monoclonal antibodies raised against the skin, cultured cells and other epithelia. Some of the molecules of the DEJ are are present in basement membrane zones of many epithelia and thus are considered ubiquitous components (type IV, V, laminin, fibronectin, nidogen, entactin, HSPG, LDA-1, CSP [3B3]). All of them (that have been investigated in developing skin) appear ontogenetically as early as human embryonic tissue can be obtained and their expression is typically normal in patients with EB. The known properties of many of these molecules (particularly the matrix components) suggest functions they might impart to the DEJ: support of an epithelium (type IV collagen), regulation of permeability (heparan sulfate proteoglycan) or facilitation of cell attachment (fibronectin) and movement (laminin). Another group of matrix components and antigens of the DEJ includes molecules that are skin-specific or characteristic of stratified squamous epithelia (type VII collagen=LH 7:2 antigen, bullous pemphigoid antigen, AA3, GB3, KF-1,19-DEJ-1, epidermolysis bullosa acquisita antigen [EBA], AF-1 and AF-2, cicatricial pemphigoid antigen [CPA]) . These molecules are expressed in the DEJ later in development than the first group of molecules, in conjunction with the morphologic appearance of the structure they represent. Their appearance is also coordinated with specific developmental events (e.g., epidermal stratification) and the expression of molecules of differentiation in the epidermis and dermis. One or more of them is typically absent or reduced in expression in the skin of patients with heritable disorders affecting this region. There is no apparent correlation between the location of molecules in the DEJ and the stability of their expression.

Case report: a child with cystic fibrosis and phenylketonuria

2020 ◽  
Vol 1 (2) ◽  
pp. 38-44
Author(s):  
Irina V. Vakhlova ◽  
Anastasia D. Kazachina ◽  
Olga A. Beglyanina
Keyword(s):  
Cystic Fibrosis ◽  
Case Report ◽  
Clinical Practice ◽  
Neonatal Screening ◽  
Genetic Disorders ◽  
Epileptiform Activity ◽  
Autism Spectrum ◽  
Speech Development ◽  
Inherited Disorders ◽  
Congenital Diseases

Background. In the international clinical practice there have been occasional reports of phenylketonuria (PKU) and cystic fibrosis (CF) found simultaneously in the same patient. Both PKU and CF are the inherited disorders characterized by autosomal recessive type of inheritance. Currently the combination of two or more inherited disorders in one patient is considered to be a clinical rarity.Case description. This is a clinical case of two genetic disorders, CF and PKU, combined in a 5-year old patient who had been followed up since birth. Owing to implementation of neonatal screening for inherited and congenital diseases into clinical practice, during the first month of life the infant was diagnosed with CF (diagnostically significant elevation of immunoreactive trypsin [IRT] at the initial [163.2 ng/mL] and repeat testing on day 21 of life [138.7 ng/mL]) and PKU (phenylalanine [PA] level 15.9 mg/dL). Both disorders have been confirmed by genetic tests, i.e., homozygous DelF508 mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and P281L mutation in the phenylalanine hydroxylase (PAH) gene was also present in homozygous state. Child’s parents strictly adhered to dietary and treatment recommendations. By the age of 5 years the child developed symptoms of neurological disorder and disorder of the respiratory system, cognitive impairment and delay in speech development, subclinical epileptiform activity with high risk of epilepsy, and chronic inflammation of the respiratory tract.Conclusion. This case report demonstrates the important role of neonatal screening in early diagnosis and timely start of therapy, and underscores the importance of continuous medication in such genetic disorders as CF and PKU. On the whole, such approach brings about a relative preservation of functioning of the most affected organs and systems. By the age of 5 years the child does not form bronchiectases, shows no signs of chronic hypoxia, nutritional deficiency or pronounced neurologic deficit, and is at low risk for the development of autism spectrum disorder. At the same time, the larger scale and longer-term observations are required in order to make the unequivocal conclusions about the prognosis of these diseases under conditions of modern-day medical follow-up.

The Accuracy of ACR TI-RADS Classification of Neck Ultrasound as a First-Line Diagnostic Approach for Thyroid Neoplasms in Pediatric Patients: A Retrospective Study

2018 ◽  
Vol 5 (1) ◽  
pp. 13-23
Author(s):  
Nikolai S. Grachev ◽  
Elena V. Feoktistova ◽  
Igor N. Vorozhtsov ◽  
Natalia V. Babaskina ◽  
Ekaterina Yu. Iaremenko ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Predictive Value ◽  
Thyroid Nodules ◽  
Pediatric Patients ◽  
Thyroid Neoplasms ◽  
Diagnostic Methods ◽  
Diagnostic Approach ◽  
First Line ◽  
Neck Ultrasound

Background.Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the gold standard in diagnosing the pathological nature of undetermined thyroid nodules. However, in some instances limitations and shortcomings arise, making it insufficient for determining a specific diagnosis.Objective.Our aim was to evaluate the effectiveness of ACR TI-RADS classification of neck ultrasound as a first-line diagnostic approach for thyroid neoplasms in pediatric patients.Methods.A retrospective analysis was made of FNA and US protocols in 70 patients who underwent the examination and treatment at Dmitry Rogachev National Research Center between January 2012 and August 2017. In the retrospective series 70% (49/70) of patients undergone FNA and 43% (30/70) of them undergone repeated FNA. All US protocols were interpreted according to ACR TI-RADS system by the two independent experts. The clinical judgment was assessed using the concordance test and the reliability of preoperative diagnostic methods was analized.Results.According to histologic examination protocols, benign nodules reported greater multimorbidity 29% (20/70), compared with thyroid cancer 17% (12/70), complicating FNA procedure. A statistically significant predictor of thyroid cancer with a tumor size ACR TI-RADS showed a significant advantage of ACR TI-RADS due to higher sensitivity (97.6 vs 60%), specificity (78.6 vs 53.8%), positive predictive value (87.2 vs 71.4%), and negative predictive value (95.7 vs 41.2%). Concordance on the interpreted US protocols according to ACR TI-RADS classification between two experts was high, excluding accidental coincidence.Conclusion.The data support the feasibility of US corresponding to the ACR TI-RADS classification as a first-line diagnostic approach for thyroid neoplasm reducing the number of unnecessary biopsies for thyroid nodules.

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