ConditionHormones & metabolism
Metabolic Disorders
A metabolic disorder is any condition that disrupts the chemical reactions the body uses to turn food into energy and building blocks, and to clear waste. Many are acquired, such as type 2 diabetes, thyroid disease and gout. Others are inherited "inborn errors of metabolism", in which a missing enzyme lets a substance build up to toxic levels or leaves the body short of something it needs. Many inherited types are found by newborn screening and controlled with diet, supplements or enzyme replacement.
Also called: Metabolic disease, inborn errors of metabolism, inherited metabolic disorders, metabolic conditions
At a glance
- What it is
- A disruption of the body's chemistry for making energy, building tissues or clearing waste.
- Acquired types
- Type 2 diabetes, metabolic syndrome, thyroid disorders, gout, obesity-related liver disease.
- Inherited types
- Hundreds of rare inborn errors such as PKU, galactosemia, urea cycle, storage and mitochondrial disorders.
- Diagnosis
- Blood and urine tests, newborn screening, genetic testing.
- Treatment
- Depends on type: diet, medicines, vitamins, enzyme replacement, organ transplant in some.
When to get help
Call 911 or go to the ER
- A newborn or infant who becomes very sleepy or floppy, stops feeding, vomits repeatedly, breathes fast or has a seizure: call 911 or your local emergency number
- A child or adult with a known metabolic disorder who is vomiting and cannot keep food or fluids down: follow the emergency letter and go to the ER
- Confusion, deep fast breathing and fruity breath in someone with diabetes (possible ketoacidosis)
See a doctor within a day or two
- An abnormal newborn screening result: call the pediatrician the same day
- A child who regresses, losing skills such as walking or talking
- A baby with jaundice, poor weight gain and vomiting after starting milk feeds
- Unusual body or urine odor (sweet, musty or sweaty-feet smell) with illness
Book a routine appointment
- Slow growth, developmental delay or unexplained muscle weakness in a child
- Thirst, frequent urination and fatigue in an adult
- Family history of an inherited metabolic disease and planning a pregnancy
What metabolism is
Metabolism is the network of chemical reactions in every cell. Enzymes, specialized proteins, drive each step, converting carbohydrates, fats and proteins into energy, building new tissue and breaking down waste. Hormones such as insulin and thyroid hormone set the pace.
A metabolic disorder occurs when one of these steps fails because:
- an enzyme is missing or faulty (usually inherited)
- a hormone is lacking or the body does not respond to it (for example, diabetes)
- an organ that handles metabolism, such as the liver, kidneys or pancreas, is damaged
Acquired metabolic disorders
These are far more common and usually develop in adulthood:
- Diabetes: high blood sugar from lack of insulin or resistance to it.
- Metabolic syndrome: a cluster of belly fat, high blood pressure, high blood sugar, high triglycerides and low HDL cholesterol that raises heart and diabetes risk. Despite the similar name, it is different from inherited metabolic diseases.
- Thyroid disorders: hypothyroidism slows metabolism; hyperthyroidism speeds it up.
- Gout: uric acid builds up and forms crystals in joints.
- Lipid disorders: high cholesterol and triglycerides.
- Fatty liver disease linked to obesity and insulin resistance.
- Metabolic bone disease: osteoporosis and osteomalacia.
Inherited metabolic disorders (inborn errors of metabolism)
More than 1,000 inborn errors are known. Each is rare, but together they are an important cause of serious illness in newborns and children. Most are inherited in an autosomal recessive pattern: both parents carry one faulty gene copy without symptoms, and each child has a 1 in 4 chance of being affected.
| Group | Examples | What goes wrong |
|---|---|---|
| Amino acid disorders | Phenylketonuria (PKU), maple syrup urine disease, homocystinuria | A protein building block builds up and damages the brain |
| Urea cycle disorders | OTC deficiency | Ammonia from protein breakdown is not cleared |
| Organic acid disorders | Methylmalonic and propionic acidemia | Toxic acids accumulate during illness or fasting |
| Carbohydrate disorders | Galactosemia, glycogen storage diseases, hereditary fructose intolerance | Sugars cannot be processed or stored properly |
| Fatty acid oxidation disorders | MCAD deficiency | Fat cannot be used for energy during fasting, causing low blood sugar |
| Lysosomal storage disorders | Gaucher, Fabry, Pompe, Tay-Sachs, mucopolysaccharidoses | Waste materials build up inside cells |
| Mitochondrial disorders | MELAS, Leigh syndrome | Cells cannot produce enough energy |
| Metal disorders | Hemochromatosis (iron), Wilson disease (copper) | A mineral accumulates in organs |
| Porphyrias | Acute intermittent porphyria | Building blocks of heme accumulate |
Symptoms
Symptoms vary enormously, but some patterns raise suspicion.
In newborns and infants
- poor feeding, vomiting and failure to gain weight
- lethargy, floppiness or irritability, progressing to coma
- seizures
- fast breathing (from acid in the blood)
- jaundice and an enlarged liver
- an unusual smell of the urine or body, such as maple syrup or musty odor
- symptoms that start after a few days of feeding, or during a minor illness
In children and adults
- episodes of vomiting, confusion or extreme tiredness triggered by fasting, infection or a high-protein meal
- low blood sugar
- developmental delay or loss of skills
- muscle weakness, cramps or exercise intolerance
- enlarged liver or spleen, heart problems, vision or hearing loss
- growth problems
Some inherited disorders, such as hemochromatosis, Fabry disease or late-onset Pompe disease, first show up in adulthood.
Diagnosis
Newborn screening
In the US, a few drops of blood from a heel prick are tested within the first days of life. The federal Recommended Uniform Screening Panel includes many metabolic disorders, such as PKU, MCAD deficiency, galactosemia, maple syrup urine disease and several lysosomal storage disorders. A positive screen is not a diagnosis; it triggers prompt confirmatory testing.
Tests when a disorder is suspected
- blood glucose, ammonia, lactate, blood gases and liver tests
- plasma amino acids, acylcarnitine profile and urine organic acids
- enzyme activity tests in blood or skin cells
- genetic testing, including gene panels and exome sequencing
- for acquired disorders: HbA1c, lipid panel, thyroid tests, uric acid, iron studies
Treatment
Treatment is tailored to the specific disorder:
- Diet: limiting the substance that cannot be processed, such as phenylalanine in PKU or galactose in galactosemia, with medical formulas to supply other nutrients.
- Avoiding fasting: frequent meals and cornstarch for glycogen storage and fatty acid oxidation disorders.
- Vitamins and cofactors: some enzymes work better with high doses of specific vitamins, such as B6 in some homocystinuria or sapropterin in some PKU.
- Medicines that remove toxins: ammonia scavengers for urea cycle disorders, chelation for Wilson disease, blood removal for hemochromatosis.
- Enzyme replacement therapy: regular infusions for Gaucher, Fabry, Pompe and some mucopolysaccharidoses.
- Transplant: liver or stem cell transplant for selected disorders.
- Gene therapy: approved for a few disorders and under study for many more.
- Emergency protocols: many patients carry a letter explaining how to treat them during illness, usually with intravenous glucose and stopping protein temporarily.
Acquired disorders are treated with lifestyle changes and medicines, such as diabetes medicines, thyroid hormone or uric acid-lowering drugs.
Outlook
Outlook depends on the disorder and how early it is treated. Children with PKU diagnosed through newborn screening and kept on diet develop normally. Other disorders can cause lasting disability despite treatment. Genetic counseling helps families understand the chances of recurrence and options for future pregnancies.
Frequently asked questions
What are the most common metabolic disorders?
The most common are acquired: type 2 diabetes, metabolic syndrome, thyroid disorders, high cholesterol and gout. Among inherited disorders, hemochromatosis is one of the most common in people of Northern European descent, while PKU and MCAD deficiency are among the most frequent found by newborn screening.
What are the symptoms of a metabolic disorder?
In babies, warning signs include poor feeding, vomiting, sleepiness, floppiness, seizures and unusual odors. In older children and adults, symptoms may include fatigue, muscle weakness, low blood sugar, developmental problems, liver enlargement, or episodes of vomiting and confusion during illness or fasting. Acquired types such as diabetes often cause thirst and frequent urination.
Are metabolic disorders genetic?
Inborn errors of metabolism are genetic, usually inherited from two carrier parents. Acquired metabolic disorders such as type 2 diabetes and gout have a genetic tendency but are strongly shaped by weight, diet and activity. Genetic testing can confirm most inherited types.
Can metabolic disorders be cured?
Most inherited metabolic disorders are lifelong but can be controlled with diet, medicines or enzyme replacement. A few can be effectively cured by liver or stem cell transplant or gene therapy. Some acquired disorders, such as type 2 diabetes, can go into remission with weight loss.
Is metabolic syndrome the same as a metabolic disorder?
No. Metabolic syndrome is a specific cluster of risk factors: belly fat, high blood pressure, high blood sugar, high triglycerides and low HDL cholesterol. "Metabolic disorder" is a broad term that includes metabolic syndrome, diabetes and hundreds of inherited enzyme disorders.
Sources
This guide was written from current patient and clinical guidance, including:
- MedlinePlus: Metabolic disorders
- MedlinePlus Genetics: Phenylketonuria
- Health Resources and Services Administration: Recommended Uniform Screening Panel
- CDC: Newborn screening
- National Organization for Rare Disorders: Inborn errors of metabolism resources