Metabolic diseases: When the eye suffers too

Metabolic diseases are often caused by genetic defects.
These include rare diseases such as Fabry disease, Pompe disease, mucopolysaccharidosis types I, II and VI, glycogen storage disease type IV, Niemann-Pick disease, Tay-Sachs disease, Gaucher disease, Krabbe disease, Canavan disease, Hurler syndrome, Hunter syndrome, Maroteaux-Lamy syndrome, mucolipidoses III/IV, Morquio syndrome, Sanfilippo syndrome and others.
Metabolic diseases are caused by a defect in one of the enzymes involved in metabolism.
In addition, many metabolic diseases are associated with certain types of cancer, particularly breast cancer.
In most cases, symptoms appear at a young age.
Some people only show signs of the disease in adulthood.
In this article, we want to inform you in particular about those diseases that can affect your eyes.

What metabolic diseases are there?

Metabolic disorders can affect not just one organ, but many different parts of the body.
They can occur in both children and adults.
Some metabolic disorders are very rare, while others are quite common.
Diabetes mellitus is one of the most common chronic diseases worldwide.
In Germany alone, around 5 million people suffer from it.
Diabetes is caused by a lack of insulin or a dysfunction of the pancreas.
Insulin regulates the metabolism of glucose in the blood.
If the production of insulin decreases or is disrupted, the blood sugar level rises.
This leads to symptoms such as thirst, hunger, fatigue, weight gain, blurred vision, dry skin and poorly healing wounds.
The following metabolic disorders are the most common:

• Diabetes mellitus
• Gout
• Hashimoto
• Cystic fibrosis
• Thyroid dysfunction

Effects of metabolic disorders

Metabolic disorders can cause a number of health problems, including Metabolic disorders: some metabolic disorders occur when an organism cannot break down certain substances or intermediates fast enough.
These substances accumulate in the body and lead to health problems.
Metabolic disorders cause a lack of certain metabolic products, which can lead to disturbances in bodily functions.
Disturbed metabolic processes can lead to altered metabolic products or intermediate products that are either harmful or unusable for the body.

Forms of metabolic disorders

There are different types of metabolic disorders.
They include several main categories, including disorders of carbohydrate metabolism, disorders of lipid metabolism, disorders of protein metabolism and disorders of mineral metabolism.
Lipid metabolism disorders include elevated cholesterol levels, carbohydrate metabolism disorders include diabetes, protein metabolism disorders include maple syrup disease and mineral metabolism disorders include phosphate deficiency.
A protein metabolism disorder is an inherited disease in which the body cannot break down certain amino acids properly.
A common example of a mineral imbalance is phosphate deficiency.
The most common form of diabetes is type 2 diabetes.
Type 2 diabetes occurs when the body’s cells no longer respond appropriately to insulin.
There are many forms of diabetes.
Some patients develop diabetes due to genetic defects.
Others develop diabetes due to a combination of environmental and genetic factors.
Metabolic diseases are often hereditary.
They develop when certain genes cause a lack of enzymes.
As a result, metabolites accumulate in the cell.
Metabolites are substances that are produced during normal metabolism.
Lysosomal storage disease is one of the most common metabolic diseases.

Lysosomal storage diseases

A lysosome is a cellular organelle that is responsible for the breakdown of waste products.
Lysosomes contain special enzymes known as acid hydrolases.
The acid hydrolases break down proteins, carbohydrates and fats into smaller molecules.
If lysosomes are damaged, they can no longer function normally.
This leads to the accumulation of undigested substances in the cell.
In addition to metabolic diseases, there are also some rare diseases that affect the eyes.
One of these is macular degeneration.
Macular degeneration affects the central part of the retina.
It is characterized by a progressive deterioration of the light-sensitive tissue of the macula.
This leads to impaired vision.
Macular degeneration is the main cause of blindness in older adults in industrialized countries.
It is caused by age-related changes in the macula.
Age-related macular degeneration (AMD) is divided into early AMD and late AMD.
Early AMD is characterized by deposits under the retina known as drusen.
Late AMD includes intermediate AMD and neovascular AMD.
Neovascular AMD is the most severe form of AMD.
It is associated with neovascularization of the choroid, i.e. abnormal growth of new blood vessels.

Diabetes mellitus

The most well-known metabolic disorder is probably type 2 diabetes mellitus, which occurs because the pancreas does not produce enough insulin.
Insulin helps the glucose to enter the cells and use it to produce energy.
When there is too little insulin, blood sugar levels rise, leading to symptoms such as increased thirst, hunger, fatigue, blurred vision, frequent urination, weight loss and slow wound healing.
There are three types of diabetes mellitus: type 1, type 2 and gestational diabetes.
Type 1 diabetes usually occurs in childhood or adolescence.
People with this form of the disease have to inject themselves with insulin every day.
Type 2 diabetes usually develops later in life, often after the age of 40.
Most people with type 2 diabetes do not know that they have the disease.
However, they develop high blood sugar levels and have similar symptoms to people with type 1 diabetes.
Gestational diabetes is another form of diabetes that affects women during pregnancy.
Women with gestational diabetes can manage their blood sugar through a healthy diet and regular exercise.
If this is not the case, they need to take medication to lower their blood sugar.

What is cystinosis?

Cystinosis is a rare hereditary metabolic disorder that primarily affects the kidneys.
This disease leads to an excessive accumulation of cystine in the cells.
As a result, patients suffer from progressive kidney failure.
In addition to the eyes, other organs such as the thyroid gland or the heart can also be affected.
Patients suffering from cystinosis often develop type 2 diabetes mellitus, osteoporosis, joint pain and muscle weakness.
In this disease, an autosomal dominant inherited genetic defect leads to an accumulation of cystine in the lysosomes of the cells.
In general, three different forms of cystinosis are distinguished: the infantile form, the juvenile form and a form that occurs in adults.
While the kidneys are primarily affected in the infantile form, only the eyes are usually affected in the adult form.
The diagnosis of cystinosis is based on clinical symptoms, laboratory findings and family history.

High cholesterol level

High cholesterol is a condition in which your blood contains too much fat (cholesterol).
This extra fat clogs the arteries and makes it harder for the heart to pump blood around the body.
It also increases the risk of having a stroke or heart attack.
Cholesterol comes from the foods you eat.
Foods that contain saturated fats, trans fats and cholesterol increase the risk of developing high cholesterol.
These include red meat, whole dairy products, butter, cheese, eggs, fried foods, snack cakes, doughnuts, pastries, margarine, peanut butter, ice cream, pizza, sausage and bacon.
The good news is that there are ways to reduce the amount of cholesterol in your diet.
You can choose lean meats instead of fatty meats, limit the amount of red meat you eat per week, eat more fish, beans and nuts, and avoid processed foods.
If you already have high cholesterol, talk to your doctor about how to lower your cholesterol.

Obesity

Obesity is a medical term used to describe an abnormal accumulation of excessive amounts of fat on the body.
In general, obesity is defined as a BMI of more than 30 kg/m2.
A person who weighs 100 pounds and is 5’7″ tall would be considered obese if their BMI is 35.5 kg/m2.
Obesity is associated with many health problems, including high blood pressure, coronary heart disease, congestion and sleep apnea.
In addition, obesity can lead to other conditions such as arthritis, osteoarthritis, gout, gallstones, varicose veins, menstrual disorders, infertility, depression, anxiety, back pain, asthma, irritable bowel syndrome, gastroesophageal reflux disease, non-alcoholic steatohepatitis and some cancers.

Causes of obesity

The causes of obesity are complex and multifactorial.
Some people have an inherited tendency to be overweight.
Others become obese due to a poor lifestyle.
Overweight people tend to consume more calories than they expend through physical activity.
They may overeat when they feel stressed or bored.
Eating large meals late in the evening can lead to weight gain.
Cigarette smoking is also associated with obesity.
Obesity is also associated with certain medications, including corticosteroids, anti-seizure medications, oral contraceptives, thyroid hormones and insulin.

Obesity with and without metabolic disorder

The most common form of obesity is simple obesity.
Simple obesity is when a person has excessive body fat but there is no underlying metabolic disorder.
People with simple obesity usually have no symptoms.
However, over time, simple obesity can cause serious health problems.
For example, a predisposition to diabetes mellitus, to name just one example.
The two can influence each other.
In some cases, obesity can be caused by an underactive thyroid gland, as well as other organic aspects such as obesity-related lymphoedema.
Some of the metabolic disorders mentioned can have negative consequences for your eyes.
There are other diseases of the internal organs that can affect your vision, such as cystinosis.

Wilson’s disease – when copper levels rise and rise

Wilson’s disease is caused by mutations in the ATP7B gene.
This gene encodes a transporter protein that plays a role in the transport of copper through the cell membrane into the bile canaliculi.
Mutations in the ATP7B gene lead to impaired function of the transporter protein, resulting in reduced excretion of copper via the bile.
As a result, copper accumulates in the body.
Copper is essential for many physiological processes, including normal metabolism, nerve conduction, bone formation and immune system function.
However, excessive amounts of copper cause serious health problems.

Symptoms of Wilson’s disease

The most common symptom of Wilson’s disease is liver dysfunction.
Other signs include neurological abnormalities, muscle weakness, psychiatric disorders, kidney failure and hemolytic anemia.
In some patients, the first sign of Wilson’s disease is a hearing or balance disorder.
People with Wilson’s disease develop copper deposits in the liver and brain.
Copper is used in many enzymes, including those involved in energy metabolism.
When these enzymes are blocked, the body can no longer use energy efficiently.
As a result, patients suffer from:

• Tiredness
• Muscle cramps
• Trembling
• Irritability
• Coordination disorders
• Memory loss
• Hearing and vision problems
• Depression
• Anxiety and
• Personality changes.

Diagnosis of Wilson’s disease

The diagnosis of Wilson’s disease requires a combination of clinical findings and laboratory tests.
A blood test called the serum ceruloplasmin level helps to determine if you have Wilson’s disease.
If this test is low (less than 0.2 g/L), then you probably do not have Wilson’s disease.
A genetic test can also help diagnose Wilson’s disease.
Your doctor will ask you about family members who have had similar symptoms.
He or she may order a DNA test to determine if you have inherited the mutation that causes Wilson’s disease.

How can Wilson’s disease be treated?

There is currently no cure for Wilson’s disease.
Treatment focuses on managing the symptoms.
Patients are treated with chelation therapy, which helps to remove excess copper from the body.
Chelation therapy involves taking a drug called D-penicillamine.
It binds to the excess copper and removes it from the body.

Mucopolysaccaridosis – when the retina degenerates

Mucopolysaccharidosis syndromes are rare genetic diseases caused by mutations in one of the three enzymes involved in glycosaminoglycan metabolism.
These enzymes break down glycosaminoglycans, complex carbohydrates found in connective tissue.
They include heparan sulfate N-deacetylase/N-sulfotransferase 2 (HS2ST2), beta-glucuronidase (GUSB) and alpha-L-iduronidase (IDUA).
Mutations in HS2ST2 cause MPS IIIA, GUSB causes MPS VII, and IDUA causes MPS I. All three diseases have similar clinical symptoms.

Porphyria – a bit of a vampire myth?

Avid fans of crime series and films will have heard of this disease at one time or another.
Whether it was a lady in “CSI” who made shakes from the organs of her victims and mused that this disease could sometimes be the cause of the vampire myth: The authors are only too happy to make use of this anomaly regarding enzyme processing.
What are porphyrias?
In porphyria, the production of heme, the iron-containing molecule responsible for oxygen transport in the body, is disrupted.
This leads to an accumulation of toxins in the liver and kidneys, causing serious health problems.
Porphyrias are hereditary diseases; however, there are also cases in which they occur spontaneously.
There are four types of porphyria: acute intermittent porphyria (AIP), variegated porphyria (VP), hereditary coproporphyria (HCP) and delta-aminolevulinic acid dehydratase deficiency (ALAD).

Various forms of prophyria

These variants differ depending on the type of enzyme deficiency.
Acute attacks are characterized by severe neurovegetative symptoms such as anxiety, depression, confusion, hallucinations, seizures, coma and even death.
In some cases, there is no specific treatment.
However, it is possible to prevent seizures by avoiding triggers such as alcohol, drugs, stress and certain foods.

Porphyria cutanea tarda (PCT)

This form of porphyria mainly occurs in women over the age of 40.
It affects the skin cells and can lead to scarring and blisters.
PCT usually begins after the menopause.
It is thought to be due to iron overload.
Iron is needed for the production of hemoglobin, but high levels of iron can damage liver cells.
In most people, the condition improves after the menopause.

Acute intermittent porphyria (AIP)

This form of porphyria occurs more frequently than PCT.
Symptoms include abdominal pain, nausea, vomiting, constipation, diarrhea, dizziness, weakness, headaches, back pain, numbness and tingling in the hands and feet.
The attacks last between 5 minutes and several hours.
People with AIP often feel better after eating fatty meals.
The most common form of porphyria is AIP.
Symptoms include abdominal pain, nausea, vomiting, constipation, diarrhea, fatigue, weakness, dizziness, headaches, confusion, memory loss, depression, anxiety, insomnia, tinnitus, hearing and vision problems.
Patients suffering from AIP usually experience episodes lasting several days to weeks.
During these periods, patients feel unwell and suffer from extreme fatigue.
They may also complain of joint pain, muscle aches and cramps.
During an attack, blisters may form under the skin, particularly in areas exposed to sunlight.
These blisters contain large amounts of urine, pus and feces.
If the infection is not treated, it can spread throughout the body and lead to sepsis.

Hemolytic uremic syndrome (HUS)

HUS is an acute kidney failure that is accompanied by bloody diarrhea, fever and other signs of infection.
HUS is caused by Shiga toxin, which is produced by bacteria that infect the intestines.
The kidneys cannot filter the blood properly because they do not have a normal lining.
This leads to swelling of the small intestine and bleeding into the bloodstream.
The first sign of HUS is usually anemia.
Other symptoms include a low platelet count, abnormal clotting factors and increased amounts of protein in the urine.
Symptoms usually appear within 10 days of the onset of the disease.
Treatment includes dialysis to remove waste products from the body and antibiotics to treat infections, if present.
In VP, porphyrins accumulate in the red blood cells, causing a dark purple coloration of the skin.
Patients may also experience itching, burning and swelling of the face, hands and feet.
Patients suffering from HCP may have similar symptoms to AIP patients, although the severity of the disease varies greatly from person to person.
In some cases, patients may even die during an attack.
In contrast, patients with ALAD do not experience any symptoms. The disturbance in blood formation can lead to Conjunctivitis come.

Diagnosis

The diagnosis is based on a clinical examination, laboratory tests, genetic tests and imaging procedures.

Treatment

Treatment depends on the severity of the seizure.
Symptomatic therapy is sufficient for mild seizures.
If necessary, anticonvulsants such as benzodiazepines and barbiturates can be used.
Antiepileptic drugs are indicated for patients with epileptic crises.
The treatment options for porphyria depend on the type of porphyria.
For example, in AIP, treatment consists of hydration, vitamin B6 supplementation, avoidance of triggers such as stress and alcohol consumption, and the use of medications such as acetylcysteine, colchicine and intravenous immunoglobulins.
In VP, treatment includes avoiding exposure to light and taking medication to reduce porphyrin production.
In HCP, the amount of porphobilinogen produced is reduced by changing the diet and taking certain medications.

Fabry disease – a hereditary defect

The disease is characterized by a deficiency of alpha-galactoside alpha-1,3-galactose, which is found in many animal tissues.
This leads to the accumulation of glycosphingolipids with terminal galactose residues in lysosomes of endothelial cells and smooth muscle cells.
These substances damage the vascular system and lead to progressive tissue destruction.

Muscle-eye-brain disease

Muscle-eye-brain disease (MEB) is a rare, severe metabolic disorder.
It often resembles a difficult and exhausting detective search.
As this is a very complex matter, we will go into it in detail in a separate article.

Metabolic diseases – not to be underestimated

Metabolic diseases often also affect the eyes.
In some cases, it may be Wilson’s disease with the characteristic Kayser-Fleisher ring in the cornea.
The diagnosis is usually made by an ophthalmologist.
Do you have any questions or do you suffer from a metabolic disease yourself?
We are at your disposal for a free consultation or an examination appointment.
The focus must always be on accurate treatment of the causative disease by specialists.
We will be happy to assist you in consultation with the doctors treating you and dedicate our efforts to the well-being of your eyes.