A to Z guide of ALL those confusing medical terms
What Are Metabolic Disorders?
Photo composite by Michela Buttignol for Verywell Health; Getty Images
Medically reviewed by Karina Tolentino, RD, CHWC
Metabolic disorders are medical conditions that impact your metabolism, a wide array of processes that enable proper bodily functioning and balance. There are two main parts to metabolism: catabolism and anabolism. Catabolism is the process of breaking down carbohydrates, protein, and fat from food, which releases energy. Anabolism is the process that uses that energy to build, repair, and grow.
Certain conditions can affect metabolism, impacting the body's ability to achieve balance, whether it be difficulty breaking down certain nutrients or regulating growth and development. These disorders may be genetic and present at birth (congenital) or develop throughout a person's lifetime.
This article will discuss the most common metabolic disorders, the causes of these diseases, and treatment options for people living with them.
Photo Composite by Michela Buttignol for Verywell Health; Getty Images
Types of Metabolic DisordersThere are hundreds of disorders that can impact different aspects of human metabolism. Most of these conditions are rare, inherited conditions, but some, like diabetes, are more common. The following are some of the most prevalent metabolic disorders.
Diabetes MellitusDiabetes impacts your body's ability to regulate blood glucose levels or blood sugar. Type 1 diabetes is an autoimmune condition in which the pancreas stops producing insulin, the hormone that helps glucose travel from the blood into cells.
In type 2 diabetes, the body will still produce insulin, but cells may become resistant to the hormone, impacting their ability to take in glucose from the blood and raising blood sugar levels.
Phenylketonuria (PKU)Phenylketonuria (PKU) is an inherited metabolic disorder that impacts the body's ability to break down phenylalanine, an amino acid found in dietary protein. People with PKU are deficient in phenylalanine hydroxylase, the enzyme needed to break down proteins that contain phenylalanine.
Maple Syrup Urine DiseaseIn maple syrup urine disease, the body cannot break down leucine, isoleucine, and valine, a group of amino acids known as branch-chain amino acids (BCAAs). BCAAs can build up to toxic levels in the blood, causing damage to the nervous system and the brain if untreated.
Story continues
HemochromatosisHemochromatosis is a disease that causes excess iron to build up in the body. This hereditary metabolic disorder causes individuals to absorb too much iron, leading to iron overload.
Urea Cycle DisordersUrea cycle disorders are a group of conditions that impact various stages of the urea cycle, the process the body uses to get rid of waste. The most common type of urea cycle disorder is ornithine transcarbamylase deficiency.
Tay-Sachs DiseaseTay-Sachs disease is an inherited condition that affects the function of an enzyme called hexosaminidase A, which is needed to metabolize a fatty compound called GM2 ganglioside. This can lead to nerve damage, blindness, deafness, and mental and physical degeneration.
Metabolic syndrome is a condition that is not caused by an autoimmune response or genetic mutation like some of these disorders. The five conditions associated with metabolic syndrome are:
To be diagnosed with metabolic syndrome, you must have at least three of the five markers.
Metabolic Disorder SymptomsThe symptoms of metabolic disorders will vary depending on the part of metabolism being impacted. Many of these conditions are evident from birth, but some symptoms may not develop until later. Common symptoms among metabolic disorders include:
What Causes a Metabolic Disorder?In many cases, metabolic disorders are caused by genetic mutations. This means that one or more genes are altered so that they no longer function properly. Genes are responsible for coding for enzymes that facilitate the metabolism of different nutrients.
For example, mutations in three genes in maple syrup urine disease code for an enzyme called branched-chain alpha-keto-acid dehydrogenase (BCAD), which breaks down BCAAs.
These genetic mutations are often passed down from one or both parents. If both parents carry one mutated recessive gene in a gene pair, though they may not have the disorder, they still can pass down the gene to their offspring, who will have the disease.
Other metabolic disorders, like diabetes, can be caused by organ dysfunction. Type 1 diabetes is considered an autoimmune disease with various contributing factors, both genetic and environmental.
How Are Metabolic Disorders Diagnosed?Most metabolic disorders are diagnosed through genetic testing, which may involve a blood draw, cheek swab, saliva sample, or heel prick in newborns. This will provide a sample of DNA that can be sequenced and checked for genetic mutations.
Genetic testing may be ordered to confirm if a healthcare provider suspects a metabolic disorder based on symptoms.
Treating Metabolic DisordersTreatment will depend on the type of metabolic disorder you have. Often diet modifications are necessary. A healthcare provider may advise limiting or restricting the nutrients or substances your body can't metabolize.
In some cases, such as with Tay-Sachs disease, treatment may focus on reducing symptoms using anti-seizure medications. In the case of type 1 diabetes, individuals must monitor their blood sugar levels and inject themselves with insulin, the hormone their body does not produce.
SummaryMetabolic disorders are a group of medical conditions that impact the metabolism, the many processes in the body that break down nutrients and convert them to energy. These disorders are often genetic and present at birth, though some may develop later. Treatment for metabolic disorders will vary but usually involve lifelong diet modifications or medication.
Inherited Disorders
It is caused by a faulty recessive allele
on chromosome 7. To be born with cystic fibrosis, a child has to inherit two copies of this faulty gene - one from each of their parents. Their parents will not usually have the condition themselves, because they will only carry one faulty gene and one that works normally.In the diagram below cystic fibrosis involves:
An individual who is homozygous
(ff) with the recessive allele will develop cystic fibrosis. Someone who is heterozygous (Ff) will be a carrier of the recessive allele, but will not develop cystic fibrosis and have no symptoms. Someone who is homozygous with the dominant allele (FF) will not develop cystic fibrosis, as you need two faulty alleles (ff) for the condition. In this combination, no faulty alleles are present. Example 1In example 1, both parents are heterozygous, Ff. The chance of them producing a child with cystic fibrosis is 1 in 4, or 25%. The parents are carriers of the disorder, and it is possible for them to produce a child with cystic fibrosis, without having it themselves. Carriers have no symptoms and are usually unaware they are carrying the recessive allele.
In example 2, only one parent (the father) has a copy of the recessive allele (Ff). There is no chance of them producing a child with cystic fibrosis. However, half the possible offspring will be homozygous, FF, and be unaffected, and half will be heterozygous, Ff and carry the recessive allele. The ratio of FF to Ff is 1:1 or 50%.
This genetic diagram shows how cystic fibrosis is inherited.
Polydactyly is an inherited condition in which a person has extra fingers or toes. It is caused by a dominant allele of a gene. This means it can be passed on by just one allele from one parent if they have the disorder.
Someone who is homozygous (PP) or heterozygous (Pp) for the dominant allele will develop polydactyly.
Offspring need to carry just one dominant allele from their parents to inherit the polydactyl condition.
The probability of the offspring having polydactyly is 50% (2 of the 4) and 50% not having it (normal). This can be expressed as a ratio, 2:2 which can be simplified to 1:1.
Genetic testsGenetic testing involves analysis of a person's DNA
Study Sheds Light On Causes Of Rare Genetic Diseases In 5,500 People
Around 5,500 people with severe developmental disorders now know the genetic cause of their condition, thanks to a major nationwide study in the U.K. That will help improve diagnosis across the world.
More than 13,500 families from 24 regional genetics services across the UK and Ireland were recruited to the Deciphering Developmental Disorders (DDD) study, a collaboration between the NHS and the Wellcome Sanger Institute.
All the families had children with severe developmental disorders that were undiagnosed despite prior testing through their national health service, and likely to be caused by a single genetic change. The Wellcome Sanger Institute sequenced all the genes in the children's and parents' genomes to look for answers, a search that is still ongoing.
Using with other high-tech methods, the team have so far been able to provide genetic diagnoses for around 5,500 children in the study, now published in the New England Journal of Medicine. The diagnoses were in over 800 different genes, including 60 new conditions previously discovered by the study. Around three-quarters of the conditions were caused by spontaneous mutations not inherited from either parent. The research team also found that the chances of success in getting a diagnosis was lower in families of non-European ancestry, reinforcing the imperative to increase research participation for under-represented groups.
Lead author Caroline Wright, Professor of Genomic Medicine at the University of Exeter, said, "Getting the right diagnosis is absolutely critical for families with rare conditions, which collectively affect around 1 in 17 people. Most of these conditions are genetic and can be diagnosed using the same genomic sequencing technology. The families in our study were desperate for answers, which can make a huge difference to clinical management and quality of life. We worked with hundreds of clinicians and scientists, as well as thousands of patients to try to find those answers. By sharing our findings, many more families in the future should get answers faster."
Senior co-author Matthew Hurles, incoming Director of the Wellcome Sanger Institute and Honorary Professor of Human Genetics and Genomics at the University of Cambridge, said responsible data sharing was critical for making the diagnoses.
He explained, "Undiagnosed patients with rare genetic diseases have the most to lose if they are not given an opportunity to participate in research and if their data are kept in silos. Many of these diagnoses were only made possible through combining data across all diagnostic centers in the UK and Ireland. For some diagnoses, it was only through sharing data with international colleagues that it was possible to make a diagnosis. As these genomic technologies move into routine healthcare, ensuring that undiagnosed patients can still benefit from research on their data will remain incredibly important."
Senior co-author Helen Firth, Professor of Clinical Genomics at the University of Cambridge and lead clinician for the study, emphasized the importance of the DECIPHER informatics platform for supporting recruitment of patients and return of diagnostic findings to clinical teams.
Professor Firth, who is also a Consultant in Clinical and Genomic Medicine at Cambridge University Hospitals NHS Foundation Trust, said, "Embedding a powerful informatics platform at the heart of this study facilitated the collaboration with families, clinicians and scientists engaged in the project, and played a crucial role in its diagnostic success and in the discovery and ultimately treatment of new causes of rare genomic disease. The Deciphering Developmental Disorders study has resulted in more than 290 publications and identified approximately 60 new disorders."
Senior co-author Michael Parker, Professor of Bioethics at the Ethox Centre at Oxford Population Health, University of Oxford, and ethics lead for the study, highlighted the key role played in the success of the Deciphering Developmental Disorders Study of an integrated program of bioethics. He said, "From the initial design of the study, through the building and sustaining of collaborative partnerships with clinicians, to the identification and addressing of practical ethical problems in real time throughout the life of the project, the embedding of ethics research and advice into the Deciphering Developmental Disorders project has been crucial to its success and to building and maintaining well-founded trust and confidence of clinicians and patients."
A similar approach to diagnosing individuals with rare diseases is now being used in the NHS by the Genomic Medicine Service, the Scottish Genomics Laboratories Network Whole Exome Sequencing Service, and the Rapid Genome Sequencing Service for acutely unwell children with a likely monogenic disorder, which can provide a genetic diagnosis for babies and children in or facing critical care within just ten days. The genetic conditions identified in the current study will feed into the tests applied by the services, to help diagnose more people swiftly.
Health Minister Will Quince said, "We're creating the most advanced genomic healthcare system in the world and this study is yet another step forward to revolutionizing care for NHS patients. Using cutting edge, high-tech methods such as this offers the potential to better understand and more accurately diagnose rare genetic conditions so children can access treatment faster and potentially limit the impact of the disease on their life."
Getting the right diagnosis can guide clinical care, and brings together families in support networks that can help guide treatment and support pathways, reducing the isolation of having a child with an ultra-rare condition.
When Jessica Fisher was given a diagnosis for her son Mungo's rare genetic disorder, she initially felt it had all come too late. Mungo's condition, called Turnpenny-Fry syndrome, was discovered in 2015 through the Deciphering Developmental Disorders study, in which he was a participant. But he was already 18, and Jessica, from St Austell in Cornwall, had been through years of uncertainty, not knowing how her son's development would unfold.
However, she took solace in being connected with another family recently diagnosed through the study, and forming a Facebook support group. Now, the group has connected around 36 families from across the world making it an invaluable community for those who are newly diagnosed.
"When I first saw a picture emailed to me of the other family's child, it was really emotional," Jessica said. "We'd always looked around for children who might look like Mungo—and here was a child in Australia who could have been his sibling. For a few months it was just us two families, but then it slowly started to grow. We now have families from countries including America, Brazil, Croatia, Indonesia… it's devastating to learn that your child has a rare genetic disorder, but getting the diagnosis has been key to bringing us together. The families are so appreciative to learn from our group, and being part of it does make us feel less isolated."
Turnpenny-Fry syndrome is caused by extremely rare changes in a gene called PCGF2. The disorder causes learning difficulties, impaired growth, and distinctive facial features that include a large forehead and sparse hair. Other common issues include feeding problems, severe constipation, and a range of potential issues in the brain, heart, circulation system and bones.
For Dasha Brogden, the support group has been a lifeline. Her daughter, Sofia, now nearly three, received a diagnosis at just one month old, when she was still in a neonatal unit. Dasha, who lives in Oxfordshire, said, "For us, getting a diagnosis really helped us to understand what to expect. Compared to families who came before the condition had an official diagnosis, we were lucky. We were given a leaflet based on the experiences of other families, and through that we knew she would need physiotherapy and occupational therapy. We learned that Sofia may have heart conditions, and a heart scan revealed that she needed surgery. She had a heart operation at 2 months old, and after that she really started to make good progress, and we were able to take her home from hospital.
"We're also incredibly grateful to be part of this community. Very few people are living through this experience, and it feels like Jessica and Mungo are like family to us. It's invaluable, and it's only been possible because they took part in the study and got a diagnosis, which is now helping others to get there much faster."
More information: Genomic Diagnosis Rare Pediatric Disease in the United Kingdom and Ireland, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2209046
Jennifer E. Posey et al, Genomics in Clinical Practice, New England Journal of Medicine (2023). DOI: 10.1056/NEJMe2302643 , www.Nejm.Org/doi/10.1056/NEJMe2302643
Citation: Study sheds light on causes of rare genetic diseases in 5,500 people (2023, April 12) retrieved 22 April 2023 from https://medicalxpress.Com/news/2023-04-rare-genetic-diseases-people.Html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
Comments
Post a Comment