Metabolism is a series of chemical events that occur in the body’s cells. These processes are in charge of nutrient breakdown and energy production in our systems.
However, one in every 1500 babies has a metabolic issue. Continue reading to learn more about the disorder known as Inborn Errors of Metabolism (IEM)
Inborn Errors of Metabolism
Inborn errors of metabolism (IEM) are a series of illnesses that result in a blockage in a metabolic pathway, which can have clinically severe effects.
These diverse illnesses can be inherited or emerge as a result of spontaneous mutations. These disorders are caused by malfunctions in the metabolic pathways that are involved in the breakdown or storage of carbohydrates, fatty acids, and proteins.
List of Inborn Errors of Metabolism
Inborn Errors of Metabolism can manifest themselves in a variety of ways. The various IEM are usually named after the enzyme that is not functioning properly. For example, if the enzyme carbamoyl phosphate synthetase 1 (CPS1) is not active, the IEM is called “CPS1 deficit”. A list of general types of IEM, as well as some examples, is provided below.
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IEM
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Examples
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Urea cycle disorders
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Ornithine transcarbamylase deficiency
Citrullinemia
Argininosuccinic aciduria
Argininemia
Carbamoyl phosphate synthetase I deficiency
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Organic acidemias
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Propionic acidemia
Methylmalonic aciduria
Isovaleric acidemia
Glutaric acidemia
Maple syrup urine disease
Alkaptonuria
Combined malonic and methylmalonic aciduria (CMAMMA)
2-hydroxyglutaric acidurias
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Fatty acid oxidation defects
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Medium chain acyl-CoA dehydrogenase deficiency
Carnitine palmitoyl transferase 1 deficiency
Long chain hydroxyacyl-CoA dehydrogenase deficiency
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Amino acidopathies
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Tyrosinemia
Phenylketonuria
Homocysteinuria
Maple syrup urine disease
Glutaric acidemia type 1
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Carbohydrate disorders
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Galactosemia
Fructosemia
G6PD Deficiency
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Mitochondrial disorders
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MELAS
MERFF
pyruvate dehydrogenase deficiency
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Disorders of porphyrin metabolism
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Acute intermittent porphyria
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Disorders of purine or pyrimidine metabolism
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Lesch–Nyhan syndrome
AMPD1 Deficiency (MADD)
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Disorders of steroid metabolism
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Lipoid congenital adrenal hyperplasia
Congenital adrenal hyperplasia
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Lysosomal storage disorders
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Gaucher’s disease
Niemann–Pick disease
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Disorders of peroxisomal function
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Zellweger syndrome
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Disorders of mitochondrial function
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Kearns–Sayre syndrome
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Inborn Errors of Metabolism As A Genetic Disorder
Image from iStock
The likelihood that another member of the family may experience the same IEM as their relative relies on the IEM’s pattern of inheritance, the family member who is at risk’s gender, and the rest of the family history (how many relatives have been diagnosed with the disorder already and whether genetic testing has been performed in other relatives).
In some circumstances, determining the likelihood that a family member at risk for the condition also has it depends on their age and whether or not they have displayed any signs or symptoms of it.
Symptoms of Inborn Errors of Metabolism
Lethargy, poor eating, vomiting, irregular breathing, seizures, and/or hypotonia are common signs of IEM in infants.
IEM must be taken into consideration in the differential diagnosis even if similar symptoms also suggest infection (including sepsis), which is more common.
Metabolic acidosis, unexplained hypoglycemia, constitutional liver dysfunction, and encephalopathy are other signs that should cause worry regarding the possibility of an IEM problem.
Because of the large number of these diseases and the vast variety of systems that are adversely affected, practically every “presenting complaint” to a healthcare professional may have a congenital metabolic disease as a possible cause, particularly in infancy and adolescence. The examples below are probable manifestations impacting each of the major organ systems.
- Growth failure, failure to grow, loss of weight
- Ambiguous genitalia, delayed puberty, precocious puberty
- Developmental delay, seizures, dementia, encephalopathy, stroke
- Deafness, blindness, pain agnosia
- Skin rash, abnormal pigmentation, lacking pigmentation, excessive hair growth, lumps and bumps
- Dental abnormalities
- Immunodeficiency, low platelet count, low red blood cell count, enlarged spleen, enlarged lymph nodes
- Many forms of cancer
- Recurrent vomiting, diarrhoea, abdominal pain
- Excessive urination, kidney failure, dehydration, oedema
- Low blood pressure, heart failure, enlarged heart, hypertension, myocardial infarction
- Liver enlargement, jaundice, liver failure
- Unusual facial features, congenital malformations
- Excessive breathing (hyperventilation), respiratory failure
- Abnormal behaviour, depression, psychosis
- Joint pain, muscle weakness, cramps
- Hypothyroidism, adrenal insufficiency, hypogonadism, diabetes mellitus
Diagnosing Inborn Errors of Metabolism
The diagnosis of IEM is challenging because the clinical presentation is often nonspecific; however, more IEM are now included in recommended newborn screening, which helps for early diagnosis. Therefore, knowledge of IEM has become essential for physicians.
Prenatal Screening
Image from iStock
Pregnant women and couples thinking about having children in the future can undergo carrier screening as part of preconception counselling, which presents the first opportunity to identify IEM.
The screening covers both IEM and non-IEM testing for people of various ethnic origins. According to the American College of Medical Genetics and Genomics, carrier screening for people of Ashkenazi Jewish origin also includes testing for Tay-Sachs disease and four additional IEM.
Inborn metabolic abnormalities can manifest in utero, in infants, kids, teens, and adults. Ultrasonography can be used to identify some IEM in utero.
A conclusive diagnosis can be made for any prenatal genetic condition, whether it was found using ultrasound or was suspected based on clinical findings, using chorionic villi sampling or amniocentesis.
Expanded Carrier Screening
Additionally, expanded carrier screening, which refers to concurrent screening for up to several hundred conditions—both IEM and non-IEM—is now recognised by ACOG as an acceptable pre-pregnancy and prenatal screening strategy for all patients. This is because DNA analysis has become less expensive, making expanded screening more affordable.
Preconception screening for inherited disorders is now available from family doctors, obstetricians, and specialists in maternal foetal medicine due to previous recommendations and decreased testing costs; however, preconception screening only finds the most prevalent DNA variants linked to a specific IEM disorder.
Consequently, the likelihood of an IEM disease is not always ruled out by a standard screening test.
Newborn Screening
IEM are most frequently found during neonatal screening. Expanded newborn screening, which currently covers 34 basic diseases, enables early treatment implementation and allows for diagnosis throughout the newborn period.
How is it done?
Newborn heel prick test | Image from iStock
The blood test will be done when your baby is roughly 24 hours old by your doctor or nurse. To obtain a few droplets of blood, they will prickle the heel of your infant. A lab receives the blood to do a metabolic disease screening. By state, different ailments are tested for. Which disorders you include in your baby’s screening is up to you. Some of them can incur additional fees.
While it usually takes a few days for the lab to process the blood test, it could take weeks for your doctor to obtain the findings. If you don’t hear back, follow up with your doctor. If at all feasible, discuss the findings with your doctor in person. Before you leave, be certain that you are aware of all the findings.
What will happen if IEM is identified?
If a metabolic problem in your infant is identified, discuss treatment options with your doctor. For some illnesses, there are effective treatment plans that can help avoid or lessen symptoms. Restricted diets, supplements, and lifestyle modifications are a few examples. Monitoring your baby’s health for signs and changes is an additional option.
However, some neonates exhibit IEM-related symptoms prior to the release of pending newborn screening findings or exhibit IEM-related symptoms that are not detected by screening.
Treating Inborn Errors of Metabolism
The most crucial course of action when treating a newborn or infant with acute decompensation caused by an IEM problem is to arrange a rapid transfer to a facility with a metabolic specialist. The following are some of the more frequent or promising therapies:
- Dietary restriction
- Dietary supplementation or replacement
- Medications
- Vitamins
- Intermediary metabolites, compounds, or drugs that facilitate or retard specific metabolic pathways
- Dialysis
- Enzyme replacement
- Gene therapy
- Bone marrow or organ transplantation
- Treatment of symptoms and complications
- Prenatal diagnosis
Can Inborn Errors of Metabolism Be Present Later In Life?
IEM occasionally appear later in life. Dysmorphic face features can develop and manifest in young children. When individuals still retain enzyme activity, it can sometimes take until adolescence or age before symptoms start to show up because they allow hazardous chemicals to slowly build up over time. For some IEM, long-term therapies are effective.
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