What Are the Normal Serum Creatine Kinase Values for Skeletal Muscle? A Worldwide Systematic Review.

Background: Serum creatine kinase (CK) has been used as a diagnostic marker for neuromuscular disorders since 1959. As manufacturer-provided normative data indicate, CK levels can be elevated in normal individuals. Recent evidence suggests these data often underestimate true CK values, which are influenced by age, race, gender, and other physiological factors.

Results of the Hungarian Newborn Screening Pilot Program for Spinal Muscular Atrophy.

The growing need to identify spinal muscular atrophy (SMA) patients as early as possible has shifted attention to newborn screening (NBS). The aim of the present study was to evaluate the possibility of including the SMA-NBS in the Hungarian screening panel. As the first step, a government-funded pilot program started in November 2022 and continued until the end of 2023.

Expanding the Phenotypic Spectrum of SPG7 Rare Damaging Variants: Insights From a Hungarian Cohort.

Mitochondria-associated paraplegin dysfunction is primarily linked to spastic paraplegia; however, genetic alterations in SPG7 have been associated with a broader spectrum of clinical symptoms. To identify disease-causing variants in the SPG7 gene, 437 patients with spastic ataxia, mitochondrial dysfunction-associated symptoms, or motoneuron lesions detected by EMG have been tested. We aimed to assess the clinical spectrum and determine the frequency of damaging variants within patient groups, particularly those less studied.

Awareness and care practices for rare neurologic diseases among senior neurologists: A global survey.

Objective: Rare neurologic diseases (RNDs) are difficult to diagnose and treat due to their low prevalence and complex nature. This survey evaluated awareness and current care status of RNDs among esteemed neurologists affiliated with the World Federation of Neurology (WFN).

Methods: A 34-question survey was distributed to renowned neurologists, including delegates from national neurology societies in the WFN Assembly, various WFN committees, and members of the Rare Neurologic Diseases Specialist group.

Insights into eye genetics and recent advances in ocular gene therapy.

The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age.

GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS.

There is no literature available about the growth differentiation factor-15 (GDF-15) biomarker in combination with mitochondrial DNA (mtDNA) deletions in insulin resistance (IR), and polycystic ovary syndrome (PCOS); however, it would be useful to achieve optimal metabolic status and improve pregnancy success. In this study, the role of GDF-15 and mtDNA deletions as biomarkers in the pathogenesis of IR and PCOS was investigated. In our study, 81 female patients who were treated for IR and/or PCOS and 41 healthy controls were included.

[Results of neonatal screening for spinal muscular atrophy in Hungary in 2023].

Introduction: Optimal health care for patients born with spinal muscular atrophy can only be achieved through neonatal screening. Neonatal screening for this incurable, progressive genetic disease that most often causes death in childhood has been introduced in many countries, and its usefulness has been proven with the outstanding results of early diagnosis and initiation of therapy. Objective: To evaluate the neonatal screening research program in Hungary, to examine the reliability, public demand, cost-effectiveness of the chosen screening method, and the health benefits of early treatment; in the case of success, proposing its automatic inclusion in the newborn screening panel.

Essential components of an effective transition from paediatric to adult neurologist care for adolescents with Duchenne muscular dystrophy; a consensus derived using the Delphi methodology in Eastern Europe, Greece and Israel.

Purpose: An increasing number of patients with Duchenne muscular dystrophy (DMD) now have access to improved standard of care and disease modifying treatments, which improve the clinical course of DMD and extend life expectancy beyond 30 years of age. A key issue for adolescent DMD patients is the transition from paediatric- to adult-oriented healthcare. Adolescents and adults with DMD have unique but highly complex healthcare needs associated with long-term steroid use, orthopaedic, respiratory, cardiac, psychological, and gastrointestinal problems meaning that a comprehensive transition process is required.

Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group.

Background And Purpose: Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature.

Probing the biological consequences of a previously undescribed de novo mutation of ZMYND11 in a schizophrenia patient by CRISPR genome editing and induced pluripotent stem cell based in vitro disease-modeling.

Background: Schizophrenia (SCZ) is a severe neuropsychiatric disorder of complex, poorly understood etiology, associated with both genetic and environmental factors. De novo mutations (DNMs) represent a new source of genetic variation in SCZ, however, in most cases their biological significance remains unclear. We sought to investigate molecular disease pathways connected to DNMs in SCZ by combining human induced pluripotent stem cell (hiPSC) based disease modeling and CRISPR-based genome editing.

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by the loss of both upper and lower motor neurons in the central nervous system. In a significant fraction of ALS cases - irrespective of family history- a genetic background may be identified. The genetic background of ALS shows a high variability from one ethnicity to another.

Multilevel evidence of MECP2-associated mitochondrial dysfunction and its therapeutic implications.

We present a male patient carrying a pathogenic MECP2 p. Arg179Trp variant with predominant negative psychiatric features and multilevel evidence of mitochondrial dysfunction who responded to the cariprazine treatment. He had delayed speech development and later experienced severe social anxiety, learning disabilities, cognitive slowing, and predominant negative psychiatric symptoms associated with rigidity.

GBA-associated Parkinson's disease in Hungary: clinical features and genetic insights.

Introduction: Parkinson's disease (PD) has a complex genetic background involving both rare and common genetic variants. Although a small percentage of cases show a clear Mendelian inheritance pattern, it is much more relevant to identify patients who present with a complex genetic profile of risk variants with different severity. The ß-glucocerebrosidase coding gene (GBA1) is recognized as the most frequent genetic risk factor for PD and Lewy body dementia, irrespective of reduction of the enzyme activity due to genetic variants.

The improvement of motor symptoms in Huntington's disease during cariprazine treatment.

Background: Huntington's disease (HD) is a progressive neurodegenerative disease, characterised by motor disturbances and non-motor (i.e., psychiatric) symptoms.

Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting.

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support.

Compound heterozygous variants in MAPK8IP3 were detected in severe congenital hypotonia mimicking lethal spinal muscular atrophy.

Mitogen-activated protein kinase 8-interacting protein 3 gene (MAPK8IP3) encodes the c-Jun-amino-terminal kinase-interacting protein 3 (JIP3) and is involved in retrograde axonal transport. Heterozygous de novo pathogenic variants in MAPK8IP3 result in a neurodevelopmental disorder with or without brain abnormalities and possible axonal peripheral neuropathy. Whole-exome sequencing was performed on an individual presenting with severe congenital muscle hypotonia of neuronal origin mimicking lethal spinal muscular atrophy.

Answer to Gerber et al. "Autosomal recessive pathogenic MSTO1 variants in hereditary optic atrophy".

Gal et al address the issues raised by Gerber et al and reiterate that patients in their study showed decreased Misato homolog 1 (MSTO1) mRNA and protein levels, but also confirm finding of Gerber et al that the mutation is in MSTO2p pseudogene. Whether MSTO2p variant contributes to the observed decrease in MSTO1 levels in patients remains unclear.

Case report: The spectrum of SMPD1 pathogenic variants in Hungary.

Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease caused by biallelic pathogenic variants in the sphingomyelin phosphodiesterase-1 () gene. Acid sphingomyelinase deficiency is characterized by a spectrum of disease and is broadly divided into three types (ASMD type A, ASMD type A/B, and ASMD type B). More than 220 disease-associated variants have been reported, and genotype/phenotype correlations are limited.

Sex steroid hormones and epilepsy: Effects of hormonal replacement therapy on seizure frequency of postmenopausal women with epilepsy-A systematic review.

Background And Purpose: Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE).

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial.

Background And Objectives: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM.