Juvenile metachromatic leukodystrophy caused by a rare genetic mutation.

Gene therapy offers new hope for children with metachromatic leukodystrophy

Chemical studies of two cerebral biopsies in juvenile metachromatic leukodystrophy: The molecular composition of cerebrosides and sulfatides

In a child with enzymatically and histopathologically proven metachromatic leukodystrophy (MLD), the disease pursued a course typical of juvenile MLD characterized by neurological degeneration beginning at age 9 years and ending in death at age 18. A younger brother of the patient was found to have profound deficiency of arylsulfatase A in leukocytes and to excrete five- to 20-fold greater-than-normal amounts of sulfatide in the urine. He was completely free of symptoms attributable to MLD until age 16 when he developed acute cholecystitis caused by sulfatide accumulation in the gallbladder. Results of detailed neurological examination at age 21 years were normal; formal psychometric assessment showed a full-scale IQ of 105 (Wechsler). Studies on cultured skin fibroblasts from the brother showed defects in arylsulfatase A activity, measured with the use of synthetic and natural substrates, and in radiolabeled sulfatide turnover. Cellulose acetate gel electrophoresis of fibroblast extracts from the patient showed no detectable arylsulfatase A isozyme under conditions that clearly distinguished pseudo-arylsulfatase A deficiency from classical MLD. Biochemically, the patient was indistinguishable from patients with classical MLD; on the other hand, his clinical course is dramatically more benign than that of his sister who was affected with severe MLD.

Metachromatic leukodystrophy (MLD) is a rare inherited disorder of the white matter with higher incidences in consanguineous populations. In children, manifestations vary with age of onset: early forms present with motor regression and developmental delay, whereas later forms begin with motor difficulties followed by behavioural or cognitive decline. We describe a 7-year-old boy with previously normal development who exhibited progressive motor deficits, speech difficulties, cognitive impairment, and loss of bladder control. Neurological examination revealed generalized hypotonia, areflexia, gait ataxia, and axial spasticity. Audiovisual function was preserved. Laboratory workup showed elevated urinary sulfatide levels despite normal enzymatic activity of the main sulfatide-degrading enzyme. Additional metabolic tests were unremarkable aside from signs of increased ketone bodies. Neuroimaging revealed white matter abnormalities consistent with a leukodystrophic process, and electrophysiological studies confirmed peripheral demyelination. Genetic analysis revealed a homozygous PSAP c.777G>A variant, affecting a gene essential for sulfatide degradation and suggesting a possible atypical form of MLD. This case highlights the diagnostic complexity of non-classical presentations and underscores the value of comprehensive metabolic and genetic evaluation. This case illustrates that MLD can present with normal enzymatic assays and highlights the importance of combined biochemical, neuroimaging, and genomic testing in children with rapid motor and cognitive decline.

Juvenile metachromatic leukodystrophy: evoked potentials and computed tomography.

Juvenile metachromatic leukodystrophy in a boy with epilepsy

Predicting clinical phenotypes of metachromatic leukodystrophy based on the arylsulfatase A activity and the ARSA genotype? - Chances and challenges.

Bardet-Biedl syndrome (BBS) is a rare genetic syndrome caused by a mutation in one of 26 different genes responsible for normal structure and/or function of primary cilia. The syndrome is characterized by multiorgan involvement with gradual onset of occurrence of clinical signs and symptoms resulting in great phenotypic variability and what is more important, often difficulties with establishing the timely diagnosis. We report a case of a one family with three members with BBS caused by a very rare mutation, a compound heterozygosity in BB12 gene. Even though all three patients have the same type of mutation, they express a significant diversity in clinical expression as well as renal impairment. This is a case report of a rare clinical syndrome caused by a very rare genetic mutation and it emphasizes the importance of genetic analysis in the timely diagnosis of oligosymptomatic patients with BBS, in order to possibly prevent long-term complications.

Detection of Mutant BRAF Alleles in the Plasma of Patients with Metastatic Melanoma

Alzheimer's disease is a neurodegenerative disease of the central nervous system. With the aging of the population, the prevalence of AD is increasing, which seriously affects the society and family. The etiology of AD is influenced by many factors, such as genetic factors and environmental factors. Among them, the influence of genetic factors accounted for dominant position. Therefore, the study of genetic factors plays an important role in the prevention and treatment of AD. In this paper, we reviewed the recent studies on genome-wide association study and rare variants of late-onset AD in different population. Key words: Alzheimer’s disease; Genome wide association study; Common mutation; Rare mutation

Holocarboxylase synthetase deficiency: report of one case.

Whole-genome exon sequencing technology is a genomic analysis method that uses target sequence capture technology to capture DNA from all exon regions of the genome for high-throughput sequencing, and has a high sensitivity for identifying disease-related low-frequency and rare mutations. Type 2 diabetes mellitus is characterized by progressive islet β-cell dysfunction and insulin resistance, and it is thought to be the result of a combination of genetic and environmental factors, in which genetic factors play an important role in the pathogenesis of type 2 diabetes. This article reviews the application of whole-genome exon sequencing in the screening of susceptibility genes and coding variants in type 2 diabetes mellitus. Key words: Exome sequencing; Diabetes mellitus, Type2; Gene mutation

This case report describes a complex presentation of dilated cardiomyopathy (DCM) in a 14-year-old boy of Indian origin, initially presenting with nonspecific abdominal pain, who was eventually found to have severe biventricular dilatation and a rare genetic mutation in PLEKHM2, associated with increased trabeculations and DCM. His condition rapidly progressed to critical cardiogenic shock, necessitating advanced heart failure therapies. This case emphasizes the importance of considering DCM in pediatric patients with atypical presentations and underscores the utility of genetic testing in identifying rare pathologic conditions. It also highlights the challenges and successful management strategies in a pediatric patient treated within an adult health care setting, demonstrating the vital role of tailored multidisciplinary approaches in managing complex cardiomyopathies. The findings contribute to the limited literature on PLEKHM2-associated cardiomyopathy.

Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the dec2 gene ( dec2 P384R ) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2 P384R mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep. To test this directly, we used a Drosophila model to study the effects of the dec2 P384R mutation on animal health. Expression of human dec2 P384R in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, dec2 P384R mutants lived significantly longer with improved health despite sleeping less. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that upregulation of pro-health pathways also contributes to the short sleep phenotype, and this phenomenon may extend to other pro-longevity models.

Kabuki Syndrome is disease derived from a rare genetic mutation that is particularly characterized by distinctive facial features, musculosketal malformations, mental retardation and cardiopulmonary anomalies and several pathologies. From anesthetic aspect, this syndrome may cause both cardiovascular and inspiratory problems, defects in palate and collum and also a number of difficulties in selecting medications and invasive procedures. Difficult intubation, prolonged neuromuscular blockage and malignant hyperthermia are frequently encountered problems in the patients with Kabuki Syndrome. An attentive examination of the patient in preoperative stage and appropriate medication preference is essential in order to prevent complications.