Review: Understanding Rare Genetic Diseases in Low Resource Regions Like Jammu and Kashmir – India
Scientists Discover Unknown Structure In Cells, Could Help Treat Thousands
A previously unknown structure discovered in our cells could pave the way toward new treatments for various genetic disorders.
The existence of the organelle—which has been dubbed the "hemifusome"—was revealed by researchers from the University of Virginia and the National Institutes of Health (NIH).
The hemifusome, the team reports, is like a "recycling center" in which the cells sort, discard and recycle important cargo.
Disruptions to these housekeeping functions underlie many inherited conditions. Understanding how this happens, the researchers say, could help treat these disorders.
One such example is Hermansky-Pudlak syndrome, which the NIH estimates may affect up to 200,000 people in the U.S.; the disorder causes symptoms including albinism, blood-clotting issues, lung disease and vision problems.
"We're just beginning to understand how this new organelle fits into the bigger picture of cell health and disease," said paper author and Virginia physiologist Professor Seham Ebrahim in a statement.
"It's exciting because finding something truly new inside cells is rare—and it gives us a whole new path to explore."
Pictured: the newly discovered organelle, the hemifusome, in yellow Pictured: the newly discovered organelle, the hemifusome, in yellow Tavakoli et al. / Nature CommunicationsThe reason that the hemifusome has never been reported before, the team says, is that the organelle comes and goes as needed by the cell.
The researchers were able to pin it down thanks to cryo-electron tomography—an imaging technique that can "freeze" cells, enabling their internal structure to be imaged in three-dimensions at a high resolution.
Hemifusomes are thought to help form both vesicles—small sacs within cells that store, transport and mix materials—as well as other organelles made up of multiple vesicles.
"You can think of vesicles like little delivery trucks inside the cell," Ebrahim said.
The hemifusome, meanwhile, "is like a loading dock where they connect and transfer cargo. It's a step in the process we didn't know existed."
Despite eluding scientists for so long, hemifusomes appear to be surprisingly common in certain parts of our cells.
With their initial study complete, the researchers are keen to learn more about the different roles that they can play.
"This is just the beginning. Now that we know hemifusomes exist, we can start asking how they behave in healthy cells and what happens when things go wrong," said Ebrahim.
"That could lead us to new strategies for treating complex genetic diseases."
Do you have a tip on a science story that Newsweek should be covering? Do you have a question about organelles? Let us know via science@newsweek.Com.
ReferenceTavakoli, A., Hu, S., Ebrahim, S., & Kachar, B. (2025). Hemifusomes and interacting proteolipid nanodroplets mediate multi-vesicular body formation. Nature Communications, 16(1), 4609. Https://doi.Org/10.1038/s41467-025-59887-9
Autosomal DNA Tests: Learn About Your Ancestry And Health - WebMD
Autosomal DNA tests are a way of looking at the code that exists inside of all of your cells. They reveal a world of genetic information that can be used medically and to discover your ethnic makeup. These tests have become popular to find relatives and ancestors.
DNA is a molecule that exists inside the cells of all living things. It contains all the information needed to create life. For example, the DNA in a cat contains all the information needed to make a cat, while the DNA of a human contains all the information to create an individual human.
The strands of DNA in your cells are tightly wound up into structures called chromosomes. You get 23 chromosomes from each of your parents for a total of 46. Of those, 44 are called autosomes and the other two are sex chromosomes. Autosomal DNA contains most of the code that makes up who you are.
By reading particular areas of this code, you can find out specific details about your genetic history. You may be able to discover the parts of the world where your ancestors lived, who those ancestors were, or information about your current family relationships and medical history.
DNA is a molecule in the shape of a double helix, which looks like a twisted ladder. The rungs of the ladder are made of smaller molecules called nucleotides. These nucleotides come in four different varieties in DNA: A, G, C, and T.
Chunks of this ladder form genes, which can be read by special machines in your cells — called enzymes — which turn them into proteins. You're mostly made of these proteins.
Mutations —or changes — can appear or be created in these genes. For example, an A could get turned into a C. This change in the code creates a change in the protein. That, in turn, could affect how your body works. The particular order of nucleotides in your genes is called your genotype, while the way these genes affect your body is called your phenotype.
There are many different services that currently offer DNA tests to find your ancestors and determine your ethnicity. Examples include 23andMe, AncestryDNA, and Family Tree DNA. DNA testing results can include information on who your ancestors are and the amounts of your DNA that come from particular ethnic groups or geographic regions.
Genealogy tests focus on your ancestors and will combine your genetic information with other sources of data, such as family trees. An ethnicity test will break your chromosomes into sections to determine the approximate ethnicity of each portion of your DNA.
For example, a result that says you're 32% Irish means that 32% of your DNA matches that of a theoretical 100% Irish person. This is ambiguous, however, because there are many genetic variations even within the Irish population.
Each service handles the testing in slightly different ways, but there are some common elements to all of them.
The first step to all DNA testing is to take a sample of your DNA. This is typically done through a swab of your cheek cells or saliva. Autosomal testing is done by looking at a subset of regions in your DNA that the companies have determined are helpful for identifying ethnic ancestry.
Typically, autosomal DNA tests look at less than 1% of your genome — around one million nucleotide sites. You have over three billion of these positions in your DNA.
While they're useful for getting information about both your mother's and father's lineage, these tests are only accurate about five or six generations back. More autosomal testing on your siblings, cousins, and second cousins can greatly increase the amount of ancestry information that you can get out of these tests.
Autosomal DNA tests can be helpful for diagnosing particular genetic diseases or predispositions for diseases. A genetic disease involves a particular mutation or sequence in your genetic code. Your doctor will look at small, specific regions of your DNA known to cause or be linked to a certain disease.
This type of testing includes:
You can get a genetic test at any age. You can even get a prenatal test if you fear that your baby may inherit a particular genetic condition.
There is some overlap between ancestry and medical genetic testing. For example, more studies are finding links between markers that indicate particular ancestries and risks for certain diseases. However, the science behind this is still in development. Consumers and sometimes even doctors are at risk for misinterpreting this information. It's important to not over-interpret the data you get from genealogy tests by treating it the same as medical DNA testing.
The accuracy of a DNA test depends on the kind of test and service. Medical tests, such as paternity and carrier testing, can give you results with 100% accuracy.
DNA testing to discover ancestry and ethnic makeup is less accurate. The same company, for example, may give you and your siblings dramatically different ethnicity percentages, or you may get very different ethnicity percentages if you use two different services. This is because there's no one right way to divide and categorize humans.
Each service will use a different algorithm and have a different set of reference genomes that they use to define particular ethnicities and geographic regions. For the most part, these tests are good at identifying large and geographically distinct ethnic groups, such as the broad categories of Native American, Sub-Saharan African, or Latin American.
But these same databases are not good at telling apart other populations that have been in close proximity for hundreds or thousands of years. French people, for example, will frequently be found to have British ancestry from a mistake in the programs.
Inherited Metabolic Disorders: Types, Signs, Causes & Treatment - WebMD
Inherited metabolic disorders are genetic conditions that result in metabolism problems. Most people with inherited metabolic disorders have a defective gene that results in lack of an enzyme. According to the latest count, 1,564 of these disorders have been identified. There are hundreds of different genetic metabolic disorders, also known as "inborn errors of metabolism."
"The impact of the disorders can vary markedly from very severe to mild depending on the type of disorder that one inherits," says Timothy Tramontana, MD, a specialist in medical genetics at the Cleveland Clinic Center for Personalized Genetic Healthcare in Cleveland, OH.
Each of these inherited metabolic disorders is individually very rare. However, when considered together, they're not so uncommon. Christina Tise, MD, PhD, an assistant professor of medical genetics at Stanford Medicine in Stanford, CA, estimates that about 1 in 100 babies are born with some type of inherited metabolic disorder. But the exact number remains unknown, she adds.
"It is hard to really know the prevalence of these conditions because newborn screening only screens for a small handful of the conditions we know about," Tise says. "It is for sure a group of genetic conditions that are underrecognized. Also the definition is not clear, and many inherited metabolic disorders are yet to be identified, are under-diagnosed, and have considerable variation in age of onset from fetus/neonate to adult."
Other factors also make it hard to get a correct count. For example, many fetuses, infants, and children with such disorders will die before they are diagnosed, Tise says. And if a disorder doesn't cause symptoms until adulthood, she adds, it may not be correctly diagnosed. Why? "They are seen as pediatric disorders even though they affect people at all ages," Tise says.
Metabolism refers to all the chemical reactions taking place in the body to convert or use energy. A few major examples of metabolism include:
Metabolism is an organized but chaotic chemical assembly line. Raw materials, half-finished products, and waste materials are constantly being used, produced, transported, and excreted. The "workers" on the assembly line are enzymes and other proteins that make chemical reactions happen.
An inherited metabolic disorder messes up the works, disrupting the assembly line. The consequences can be very bad.
These disorders affect "the breakdown or synthesis of proteins, lipids and sugars essential for the normal function of our body," says Eva Morava, MD, PhD, the director of the Inherited Metabolic Diseases Program at the Icahn School of Medicine at Mount Sinai in New York City, NY. "Untreated, these disorders can lead to multiorgan failure and death."
In most inherited metabolic disorders, a single enzyme is either not produced by the body at all or is produced in a form that doesn't work. The missing enzyme is like an absentee worker on the assembly line. Depending on that enzyme's job, its absence means toxic chemicals may build up or an essential product may not be produced.
The code or blueprint to produce an enzyme is usually contained on a pair of genes. Most people with inherited metabolic disorders inherit two defective copies of the gene — one from each parent. Both parents are "carriers" of the bad gene, meaning they carry one defective copy and one normal copy.
In the parents, the normal gene copy compensates for the bad copy. Their enzyme levels are usually enough, so they may have no symptoms of a genetic metabolic disorder. But the child who inherits two defective gene copies cannot produce enough effective enzymes and develops the genetic metabolic disorder. This form of genetic transmission is called autosomal recessive inheritance.
The original cause of most genetic metabolic disorders is a gene mutation that occurred many generations ago. The gene mutation is passed along through the generations, ensuring its preservation.
Each inherited metabolic disorder is very rare in the general population. But considered together, inherited metabolic disorders may affect about 1 in 1,000 to 2,500 newborns. In certain ethnic populations, such as in Ashkenazi Jews with central and eastern European ancestry, the rate of inherited metabolic disorders is higher.
Hundreds of inherited metabolic disorders have been identified, and new ones continue to be discovered. Some of the more common and important genetic metabolic disorders include:
Lysosomal storage disorders . Lysosomes are spaces inside cells that break down waste products of metabolism. Various enzyme deficiencies inside lysosomes can result in buildup of toxic substances, causing metabolic disorders including:
Galactosemia. Impaired breakdown of the sugar galactose leads to jaundice, vomiting, and liver enlargement after breast or formula feeding in a newborn.
Maple syrup urine disease . Deficiency of an enzyme called BCKD causes buildup of amino acids in the body. This results in nerve damage, and the urine smells like syrup.
Phenylketonuria (PKU). Deficiency of the enzyme PAH results in high levels of phenylalanine in the blood. Intellectual disability results if the condition is not recognized.
Glycogen storage diseases. Problems with sugar storage lead to low blood sugar levels, muscle pain, and weakness.
Mitochondrial disorders. Problems inside mitochondria, the powerhouses of cells, lead to muscle damage.
Friedreich ataxia. Problems related to a protein called frataxin cause nerve damage and often heart problems. Inability to walk usually results by young adulthood.
Peroxisomal disorders. Similar to lysosomes, peroxisomes are tiny spaces filled with enzymes inside cells. Poor enzyme function inside peroxisomes can lead to buildup of toxic products of metabolism. Peroxisomal disorders include:
Metal metabolism disorders. Levels of trace metals in the blood are controlled by special proteins. Inherited metabolic disorders can result in protein malfunction and toxic accumulation of metals in the body. Metal metabolic disorders include:
Organic acidemias. Examples include methylmalonic acidemia and propionic acidemia.
Urea cycle disorders. Examples includeornithine transcarbamylase deficiency and citrullinemia.
The symptoms of genetic metabolic disorders vary widely depending on the metabolism problem present. Some symptoms of inherited metabolic disorders include:
The symptoms may come on suddenly or progress slowly. Symptoms may be brought on by foods, medications, dehydration, minor illnesses, or other factors. Symptoms appear within a few weeks after birth in many conditions. Other inherited metabolic disorders may take years to develop symptoms.
Inherited metabolic disorders are present at birth, and some are detected by routine screening. All 50 states screen newborns for phenylketonuria. Most states also test newborns for galactosemia. But no state tests babies for all known inherited metabolic disorders.
Improved testing technology has led many states to expand newborn screening for genetic metabolic disorders. The National Newborn Screening and Genetics Resources Center provides information on each state's screening practices.
If an inherited metabolic disorder is not detected at birth, it's often not diagnosed until symptoms appear. Once symptoms develop, specific blood or DNA tests are available to diagnose most genetic metabolic disorders. Being referred to a specialized center (usually at a university) increases your chances of a correct diagnosis.
But as Tise points out, these disorders are often thought of as affecting children, so they may not be on your doctor's list of possible suspects if you don't show symptoms until adulthood.
Limited treatments are available for inherited metabolic disorders. The essential genetic defect causing the condition can't be corrected with the technology we have right now. Instead, treatments try to work around the problem with metabolism.
"There are presently therapies used for some of the inherited metabolic disorders that are quite efficacious, including medications and dietary therapy, and can help to varying degrees of effect depending on the particular disorder," Tramontana says.
But, he continues, many of these disorders have no treatment, and for those that do, such treatments may not have much evidence to support their use.
Treatments for genetic metabolic disorders follow a few general principles:
Treatment may include such measures as:
Whenever possible, a person with an inherited metabolic disorder should get care at a medical center experienced with these rare conditions.
Children and adults with inherited metabolic disorders can become very ill, requiring hospitalization and sometimes life support. Treatment during these episodes focuses on emergency care and improving organ function.
Experts continue to search for effective ways to treat these disorders.
"There are new and promising therapies coming out in the realm of gene therapy, enzyme replacement therapy, and prenatal therapies in fetuses with a known diagnosis," Tise says.
Inherited metabolic disorders are individually very rare, but taken together, they affect many people. Their impact on people's health varies widely. While some may cause only mild symptoms, others are fatal. How treatable these disorders are also varies, but there's hope that future therapies will effectively treat a growing number of these disorders and, perhaps, provide a cure.
How rare are inherited metabolic disorders?
Each disorder is very rare on its own. Taken together, they add up, though to what number remains uncertain. Studies published over the last two decades suggest they're less common, ranging from 1 in 800 to 1 in 2,000 in live births. But Tise estimates that as many as 1 in 100 babies may be born with an inherited metabolic disorder. Why? For many reasons, she says, including that many of these disorders go unrecognized or undiagnosed.
Is Crohn's disease an inherited metabolic disorder?
No, Tramontana says. While certain genes have been linked to Crohn's, the disease has no known cause. It's considered an autoimmune inflammatory disease, not an inherited metabolic disorder.
What are the most common inherited metabolic disorders?
The most common include:
What inherited metabolic disorders cause weight gain?
Metabolic disorders are more likely to cause weight loss or make it difficult to gain weight. But in some disorders you need to eat frequently in order to prevent complications such as hypoglycemic crisis, or dangerously low blood sugar levels, Tramontana says. This can lead to weight gain. He points to one such disorder: medium chain acyl-CoA dehydrogenase deficiency (MCADD). This disorder prevents your body from converting certain fats into energy. "[It] requires frequent feeding early in life that could result in overindulgence in calories and weight gain," Tramontana says.
Can inherited metabolic disorders be cured?
Not yet, though finding cures is the eventual goal, Tramontana says.
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