Príznaky postihnutia nervového systému sú veľmi často spojené s geneticky podmienenými chorobami. Dedičné metabolické poruchy alebo vrodené poruchy metabolizmu predstavujú heterogénnu skupinu, pričom je už opísaných viac ako 1000 chorobných jednotiek. Patria medzi zriedkavé choroby a časť z nich sa manifestuje aj neurologickou symptomatológiou - neurometabolické ochorenia. Rozšírenie škály DNA vyšetrovacích metód umožňuje spoľahlivú diagnostiku mnohých ochorení. Vzhľadom na početnosť neurometabolických porúch možno v limitovanom rozsahu publikácie prezentovať iba časť vybraných poznatkov, pričom preferenčne sú uvedené tie, ktoré sa manifestujú v dospelom veku a sú terapeuticky dobre ovplyvniteľné. Cieľom práce je poskytnúť stručný prehľad. Získané informácie sú cenné aj pre genetickú konzultáciu postihnutých rodín.

The symptoms of the nervous system are very often associated with genetic diseases. Inborn errors of metabolism represent a heterogeneous group with more than 1000 disorders. These are rare disorders and some of them are also manifested by neurolo­gical symptomatology - called as neurometabolic diseases. Genetic diagnostics is based on variety of DNA techniques and enables reliable diagnosis of many diseases. Due to the wide range of inborn errors of metabolism only a selected part is presented. We focus on disorders which are manifesting in adulthood and can be positively influenced by causal therapeutic approach. The aim of the work is to provide a brief overview. The information obtained is also valuable for genetic counselling in affected families.

• MeSH
• Adrenoleukodystrophy diagnosis   genetics   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Genetic Testing methods   MeSH
• Case Reports as Topic MeSH
• Humans MeSH
• Brain Diseases, Metabolic diagnosis   genetics   classification   MeSH
• Ornithine Carbamoyltransferase Deficiency Disease diagnosis   genetics   MeSH
• Neurologic Manifestations * MeSH
• Neonatal Screening methods   MeSH
• Metabolism, Inborn Errors * diagnosis   genetics   classification   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Review MeSH

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.

• MeSH
• Ammonia metabolism   MeSH
• Arginine therapeutic use   MeSH
• Citrulline MeSH
• Hyperammonemia * drug therapy   MeSH
• Carbamyl Phosphate metabolism   therapeutic use   MeSH
• Carbamoyl-Phosphate Synthase (Ammonia) metabolism   MeSH
• Humans MeSH
• Ornithine Carbamoyltransferase Deficiency Disease * surgery   MeSH
• Ornithine Carbamoyltransferase MeSH
• Retrospective Studies MeSH
• Liver Transplantation * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH

Studies from the last decades indicate that increased levels of ammonia contribute to muscle wasting in critically ill patients. The aim of the article is to examine the effects of two different causes of hyperammonemia-increased ATP degradation in muscles during strenuous exercise and impaired ammonia detoxification to urea due to liver cirrhosis. During exercise, glycolysis, citric acid cycle (CAC) activity, and ATP synthesis in muscles increase. In cirrhosis, due to insulin resistance and mitochondrial dysfunction, glycolysis, CAC activity, and ATP synthesis in muscles are impaired. Both during exercise and in liver cirrhosis, there is increased ammonia detoxification to glutamine (Glu + NH3 + ATP → Gln + ADP + Pi), increased drain of ketoglutarate (α-KG) from CAC for glutamate synthesis by α-KG-linked aminotransferases, glutamate, aspartate, and α-KG deficiency, increased oxidation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine), and protein-energy wasting in muscles. It is concluded that ammonia can contribute to muscle wasting regardless of the cause of its increased levels and that similar strategies can be designed to increase muscle performance in athletes and reduce muscle loss in patients with hyperammonemia. The pros and cons of glutamate, α-KG, aspartate, BCAA, and branched-chain keto acid supplementation are discussed.

• Publication type
• Journal Article MeSH
• Review MeSH

Poruchy autistického spektra (PAS) se projevují v oblasti sociálních interakcí, komunikace a chování. Diagnózu autismu má stanovit za použití specializovaného psychologicko-psychiatrického vyšetření, které zahrnuje minimálně dvě standardizované metody, pouze erudovaný psycholog nebo psychiatr, který se touto problematikou dlouhodobě zabývá. Každý pacient s PAS by však měl být komplexně vyšetřen, aby byla zjištěna buď etiologie obtíží, nebo komorbidita skrytá pod obrazem autistických projevů. Rozmanitost diagnóz, které mohou být příčinou autistických projevů pacienta, dokumentují tři diametrálně rozdílné kazuistiky z praxe.

Autism spectrum disorders (ASDs) are manifested in the area of social interactions, communication, and behaviour. The diagnosis of autism is to be made by an experienced psychologist or psychiatrist who has had long expertise in this field, using a specialized psychological-psychiatric testing which involves at least two standardized methods. However, every ASD patient should undergo comprehensive evaluation in order to ascertain either the aetiology of the symptoms or the comorbidity obscured by autistic symptomatology. The diverse diagnoses that can cause autistic symptoms in a patient are documented by three entirely different case reports from the practice. ses that can cause autistic symptoms in a patient are documented by three entirely different case reports from the practice.

• MeSH
• Autistic Disorder * diagnosis   etiology   MeSH
• Diagnosis, Differential MeSH
• Muscular Dystrophy, Duchenne diagnosis   MeSH
• Comorbidity MeSH
• Humans MeSH
• Brain Neoplasms surgery   diagnosis   MeSH
• Child, Preschool MeSH
• Rett Syndrome diagnosis   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Dystonic Disorders diagnosis   genetics   therapy   MeSH
• Huntington Disease diagnosis   genetics   therapy   MeSH
• Humans MeSH
• Neuroaxonal Dystrophies etiology   genetics   MeSH
• Neurodegenerative Diseases * diagnosis   etiology   pathology   therapy   MeSH
• Parkinsonian Disorders diagnosis   etiology   drug therapy   MeSH
• Rett Syndrome diagnosis   genetics   therapy   MeSH
• Spastic Paraplegia, Hereditary diagnosis   genetics   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Antipsychotic Agents administration & dosage   adverse effects   therapeutic use   MeSH
• Adult MeSH
• Hepatocytes drug effects   MeSH
• Hyperammonemia chemically induced   diagnosis   etiology   MeSH
• Clozapine administration & dosage   adverse effects   therapeutic use   MeSH
• Valproic Acid * adverse effects   MeSH
• Chemical and Drug Induced Liver Injury * diagnosis   etiology   prevention & control   MeSH
• Humans MeSH
• Schizophrenia, Paranoid drug therapy   complications   MeSH
• Reye Syndrome etiology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Asperger Syndrome diagnosis   etiology   therapy   MeSH
• Autistic Disorder diagnosis   etiology   therapy   MeSH
• Intelligence Tests MeSH
• Humans MeSH
• Adolescent MeSH
• Neuropsychological Tests MeSH
• Neurodevelopmental Disorders * diagnosis   etiology   therapy   MeSH
• Child Development Disorders, Pervasive diagnosis   etiology   classification   therapy   MeSH
• Autism Spectrum Disorder diagnosis   etiology   psychology   therapy   MeSH
• Motor Skills Disorders diagnosis   etiology   therapy   MeSH
• Learning Disabilities diagnosis   etiology   therapy   MeSH
• Child, Preschool MeSH
• Rett Syndrome diagnosis   etiology   genetics   MeSH
• Treatment Outcome MeSH
• Language Development Disorders diagnosis   etiology   therapy   MeSH
• Developmental Disabilities diagnosis   etiology   therapy   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Publication type
• Case Reports MeSH

Článek shrnuje klinickou manifestaci, diagnostiku a léčbu poruch cyklu močoviny s důrazem na použití Arginin Chloridu v léčbě hyperamonémie. Na závěr přináší dvě kazuistiky nejčastější z poruch cyklu močoviny, deficitu ornithintranskarbamoylázy.

The text presents a short overview of clinical manifestation, diagnostics and therapy of urea cycle disorders, emphasises the role of Arginin chloride in the therapy of hyperammonemia. Two case reports of one of the most frequent type of urea cycle disorders, ornithin transcarbamylase deficiency, are presented at the end.

• MeSH
• Arginine therapeutic use   MeSH
• Hyperammonemia * diagnosis   therapy   MeSH
• Humans MeSH
• Adolescent MeSH
• Ornithine Carbamoyltransferase Deficiency Disease * diagnosis   physiopathology   therapy   MeSH
• Infant, Newborn MeSH
• Ornithine Carbamoyltransferase analysis   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Infant, Newborn MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Child MeSH
• Dystonic Disorders genetics   physiopathology   MeSH
• Genetic Techniques MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Cerebral Palsy * genetics   MeSH
• Child, Preschool MeSH
• Rett Syndrome genetics   physiopathology   MeSH
• Spastic Paraplegia, Hereditary genetics   physiopathology   MeSH
• Ataxia Telangiectasia genetics   physiopathology   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

BACKGROUND: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder manifesting with high serum ferritin levels and the formation of early-onset cataracts, with numerous small opacities, predominantly in the lens cortex. HHCS is caused by mutations in the iron-responsive element of the FTL gene. The aim of this study was to establish a molecular diagnosis in three Czech probands with suspected HHCS. METHODS: A complex ocular and systemic evaluation, including ferritin and iron measurements, was performed. The 5' untranslated region of FTL was directly sequenced in all available family members, followed by paternity testing in one family. RESULTS: Three different FLT pathogenic variants (c.-161C>T, c.-167C>T, and c.-168G>C) present in the heterozygous state were detected in each of the 3 probands. Two segregated with the disease phenotype within the families, but c.-167C>T occurred de novo (confirmed by paternity testing). Prior to establishing molecular diagnosis, two probands were misdiagnosed with hemochromatosis. One individual, aged 43 years, underwent phlebotomy; another, aged 8.5 years, was treated with the iron chelator deferasirox, leading to life-threatening acute hyperammonemia, without severe liver injury. CONCLUSIONS: Lack of family history does not exclude HHCS, because the pathogenic variant can arise de novo. Noncoding regions are often omitted from diagnostic gene panels, thus evading detection. Careful clinical evaluations and targeted genetic screening are important for avoiding potentially harmful treatments.

• MeSH
• Apoferritins genetics   MeSH
• Hyperferritinemia * MeSH
• Cataract * diagnosis   genetics   MeSH
• Humans MeSH
• Molecular Biology MeSH
• Mutation MeSH
• Pedigree MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH