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- Alström Syndrome (ALMS)
The multifactorial nature and infrequency of Alström Syndrome (ALMS) result in a delayed diagnosis and insufficient therapy, which emphasizes the need for tailored therapeutic and diagnostic strategies. Protheragen offers comprehensive diagnostics and therapeutics development services for Alström Syndrome, leveraging cutting-edge technologies and expertise in rare genetic disorders.
Alström Syndrome (ALMS) is a genetic disorder that is extremely rare and is caused by an abnormality in the ALMS1 gene, which undergoes ciliary function as well as intracellular trafficking. This disorder encompasses multiple systems and is clinically visible as progressive vision impairment due to cone-rod dystrophy, hearing loss, childhood obesity, severe insulin resistance, type 2 diabetes, hypertriglyceridemia, decreased height, and progressive cardiac dysfunction and failure of lungs, liver, and kidneys. Symptoms of the disorder are usually observed during infancy but tend to vary from individual to individual, even within the same family.
Fig.1 Case analysis of Alström Syndrome. (Hanaki K., et al., 2024)The pathogenesis of Alström Syndrome has been shown to be directly related to the malfunctioning of the ALMS1 protein, which is found at the centrosomes and basal bodies of ciliated cells. This particular protein is important in both the formation and maintenance of cilia which, in turn, have important roles in numerous cellular signaling pathways. ALMS1 mutations are known to cause truncation or loss of function of the protein which inevitably leads to defective ciliogenesis and non-functional ciliary systems. Such cellular process impairments cause the myriad symptoms associated with ALMS.
Genetic Testing
Identifying ALMS requires genetic testing to delineate biallelic pathogenic variants in the ALMS1 gene, which is a cornerstone of ALMS diagnostics. The targeted sequencing of hotspot exons 8, 10 and 16 is often used because of the high prevalence of mutations in these regions. Comprehensively and cost-effective screening options have been made possible with the advent of next-generation sequencing (NGS) technologies like whole-exome sequencing (WES) and targeted gene panels which have transformed the detection of ALMS1 mutation. Known screening for mutations in ALMS1 and other genes associated with ciliopathy has also been done efficiently using arrayed primer extension (APEX) technology.
Functional Assays
Functional assays utilizing cells obtained directly from patients can shed light on ALMS's pathophysiology. These assays evaluate ciliary activity, intracellular transport processes, and metabolism influenced by ALMS1 mutations. For example, some studies have shown that cells from ALMS patients exhibit defective ciliogenesis and abnormal centrosome activities. Also, insulin resistance, in combination with hyperinsulinemia, can be studied through various steps of metabolic profiling and insulin signaling assays.
Protheragen's diagnostics and therapeutics development services are characterized by their scientific rigor, technological innovation, and customized approach. Our state-of-the-art genetic testing capabilities, coupled with advanced functional assays and non-invasive imaging, provide comprehensive insights into ALMS pathophysiology. Our preclinical research services offer a robust platform for the development of novel therapies, ensuring a seamless transition from bench to bedside.
Protheragen's key advantage in Alström Syndrome diagnostics and therapeutics development lies in our comprehensive capabilities, deep expertise in rare diseases, and commitment to customized solutions. If you are interested in our services, please feel free to contact us.
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