What is Inborn Errors of Metabolism?
Inborn errors of metabolism are a variety of conditions that can be either inherited or result from spontaneous genetic changes. These illnesses are due to failures in the body’s metabolic processes, which are necessary in either breaking down or storing substances such as carbohydrates, fats, and proteins. Even though a single type of inborn error of metabolism is very rare, combined, these diseases occur in about one in 2,500 births, making them relatively common. They can appear at any age, so having a basic understanding of these diseases, their symptoms, and how to evaluate them is crucial for healthcare professionals working in an emergency setting.
What Causes Inborn Errors of Metabolism?
Inborn errors of metabolism are genetic disorders that happen because of changes or mutations in certain genes. These genes are responsible for making proteins that help your body’s metabolism. This means they aid in the process of breaking down food and turning it into energy. Typically, these disorders are inherited in a manner known as autosomal recessive inheritance. This means a person must inherit a copy of the faulty gene from both of their parents in order to have the disorder.
Sometimes, these conditions can be inherited in other ways, such as autosomal dominant or X-linked inheritance. In autosomal dominant inheritance, getting a fault gene from just one parent is enough for a person to have the disorder. In X-linked inheritance, the gene causing the disease is located on the X chromosome – one of the two sex chromosomes that determine a person’s gender.
Besides genes, there are other factors which can influence these metabolic disorders. These factors can include the environment, changes in other genes, the state of a person’s epigenomes (which control when and how a gene is turned on or off), and the community of microorganisms living in and on the human body, referred to as the microbiome.
Risk Factors and Frequency for Inborn Errors of Metabolism
Inborn errors of metabolism are rare conditions that happen in about 1 out of every 2500 births. These conditions are different from each other in terms of how they appear, how common they are, and how they’re passed down from parents to children. For example, mitochondrial disorders are always passed down from a mother to all her children, but other conditions can vary or could be linked to a specific sex. Inborn metabolic errors could cause an enzyme to completely stop working, or they might cause it to not work properly.
Newborn babies are often screened for these disorders shortly after birth, but the number of diseases they’re tested for can vary from hospital to hospital. Tests can pick up between 8 to 50 different diseases, but there are actually thousands of possible conditions. Also, it’s important to know that these tests can sometimes miss a disease if the baby is tested too soon after birth or if they’ve had a blood transfusion. Because of these factors, half of all inborn errors show up after the newborn period, and some aren’t found until adulthood.
- Inborn errors of metabolism occur in 1 out of 2500 births.
- These disorders vary in how common they are, how they appear, and how they’re inherited.
- For instance, all children of a mother with a mitochondrial disorder will also have the disorder.
- These conditions can cause an enzyme to stop working or not work properly.
- Newborn screening can identify 8 to 50 different conditions, but there are thousands of possible diseases.
- Sometimes, these tests may not detect a disease if the baby is tested too soon after birth or has received a blood transfaction.
- Half of all inborn errors show up after the newborn period.
- Some conditions aren’t detected until adulthood.
Signs and Symptoms of Inborn Errors of Metabolism
Severe errors in carbohydrate metabolism can have serious implications for infants. These infants may experience symptoms similar to severe infections, including low blood sugar, abnormal heart rhythms, abnormal body temperature, seizures, and decreased muscle tone. In most cases, they find it difficult to convert food into energy. Unfortunately, the condition often worsens if it presents early on.
Similarly, individuals with severe administration errors usually show symptoms of intoxication. These include lethargy, altered mental state, seizures, vomiting, and vital signs abnormalities. They also often exhibit higher levels of ammonia and other metabolites in their blood. Patients who struggle with accessing stored energy may remain well for a long time and can be symptom-free as long as they have a regular intake of carbohydrates. However, during times of illness, diet change, or decreased feeding, they may experience low blood sugar or seizures. These children may appear very sick even with minor, brief illnesses.
Generally, metabolic disorders manifest variably depending on the extent and type of enzyme involved. However, a few common features exist. These diseases most often result in neurological abnormalities, affecting about 80% of patients. These abnormalities involve developmental delays, loss of developmental milestones, poor muscle tone, underdeveloped sucking reflex, and seizures.
- Developmental delays
- Loss of developmental milestones
- Poor muscle tone
- Underdeveloped sucking reflex
- Seizures
The second most common symptoms relate to the gastrointestinal system. Symptoms include vomiting, enlarged liver, food intolerance, diarrhea, food aversion, exercise intolerance, and dehydration. Over half of the affected children display both neurological and gastrointestinal abnormalities. Hence, children showing signs of these abnormalities should be tested for metabolic disorders. This should also be considered for children facing continuous feeding issues, frequent formula changes, supposed reflux or gastroparesis, irregular body functions, and behavioral or learning difficulties.
Testing for Inborn Errors of Metabolism
Although it’s not easy to definitively diagnose metabolic disorders that are inherent from birth (inborn errors of metabolism) during a medical emergency, blood tests are still very important. This is because the abnormal results might be temporary so doctors usually collect enough blood to carry out future tests. Even though the emergency department might not be able to pinpoint the exact disorder, certain laboratory tests can provide valuable hints.
Most children with these disorders tend to have specific results in both blood and urine tests. They may have high lactate level, low blood sugar (hypoglycemia), high blood ammonia (hyperammonemia), or high acidity in the blood (acidosis). Urine tests may show ketones or other substances at elevated levels. These tests can be used to screen for potential metabolic disorders. If the tests show any abnormal sign, the doctor might decide to carry out more detailed blood tests to measure specific amino acids and organic acids for further investigation.
If the child is going to have a lumbar puncture (a process where fluid is collected from the spine), doctors often store additional spinal fluid for future tests as well.
Treatment Options for Inborn Errors of Metabolism
If a patient is suspected to have an inborn error of metabolism, their initial treatment would likely involve strong revitalization steps, much like those found in the PALS/ACLS procedures. It’s crucial that these patients don’t eat or drink anything as it’s uncertain which part of their metabolic process may be affected.
The healthcare provider’s goal here is to prevent the patient’s own metabolic pathways from being used. These pathways are responsible for processing carbohydrates, removing by-products, or accessing stored energy. Instead, pure glucose, which acts as a direct source of energy (substrate), is provided to the patient. This helps decrease the need for the patient to break down body-stored energy sources like glycogen or fatty acids. A 10% dextrose solution is usually used for this purpose.
In some cases, patients might develop a high blood sugar level (hyperglycemia) due to the provided glucose, so insulin may be administered to control it. If a patient shows high levels of ammonia—a toxic substance—the healthcare provider may use certain medications like sodium benzoate or sodium phenylacetate to help clear it. However, if the ammonia levels are extremely high (greater than 600), a process called dialysis is used to clean the blood.
Patients suspected of having metabolic errors are usually quite sick and often need to be monitored in the intensive care unit (ICU) of a hospital.
What else can Inborn Errors of Metabolism be?
Here are some important topics related to pediatric and medical conditions that need immediate attention:
- Emergency care for children with fever
- Heart failure
- Use of medical imaging in cases of restrictive cardiomyopathy
- Migraine headaches
- Multiple sclerosis
- Apnea in children
- Pyloric stenosis in children
- Urinary tract infections in children
- Managing a crying child
- Low blood sugar (hypoglycemia) in children
