What is Acrodermatitis Enteropathica (Zinc Deficiency)?
Acrodermatitis enteropathica (AE) is a condition inherited from your parents that results from a lack of the nutrient zinc in the body. Zinc is critical for our health as it helps over two hundred enzymes in our body function properly, participating in several metabolic and biochemical pathways. The reason for zinc deficiency in AE is due to changes or mutations in the gene named SLC39A4 that helps in the absorption of zinc from our food.
AE was first mentioned by a scientist named Brandt in 1936, and later recognized as a unique disease by Danbolt and Closs. Importantly, we should know that zinc deficiency could also occur due to poor nutrition, problems with the absorption of nutrients from food, liver or kidney diseases, and some medical treatments, which can cause symptoms similar to AE.
What Causes Acrodermatitis Enteropathica (Zinc Deficiency)?
The SLC39A4 gene, located on chromosome 8q24.3, is responsible for making a protein called ZIP 4. This protein is involved in absorbing zinc from outside the cell into the cell. Think of it as a door that allows zinc to enter the cell where it can be used by other proteins. If a mistake (mutation) occurs in this gene in a way that it is passed on from both parents (autosomal recessive mutation), the “door” doesn’t work properly. As a result, the body struggles to absorb zinc, and people with this mutation can experience symptoms of zinc deficiency.
There’s another gene called SLC30A2 on chromosome 1p36.11, and a mutation in it has been noticed in some mothers. This mutation affects the way zinc is secreted into breast milk, meaning that it could lead to less zinc in the milk.
Risk Factors and Frequency for Acrodermatitis Enteropathica (Zinc Deficiency)
Acute Encephalopathy (AE) is a condition that affects somewhere between 1 to 9 in every 1,000,000 people globally. This translates to 1 in every 500,000 newborns. It can affect anyone, regardless of their ethnic background or gender. The condition usually shows up during infancy, particularly when babies stop breastfeeding and start eating solid food. For babies who are fed with formula, the condition can appear even earlier. However, a type of AE that is caused by a lack of zinc can occur at any age.
Signs and Symptoms of Acrodermatitis Enteropathica (Zinc Deficiency)
Acrodermatitis enteropathica is a condition that generally shows symptoms in infants at the time of weaning from breastfeeding, or even earlier in formula-fed babies. In rare cases, a child who is being breastfed may start showing symptoms before weaning due to a genetic issue in the mother that reduces the amount of zinc in her breast milk.
The condition affects the skin, causing defined, dry, scaly, red skin patches typically around the mouth, nose, and the area around the anus and genitals. These patches can take on various forms, such as being similar to psoriasis or eczema, forming blisters, pustules, or erosions with a crusted border. The patches usually spare the upper lips. There could be changes to the nails, including inflammation around the nails, and the hair becoming brittle, dry and losing its shine. In severe cases, the hair may start falling out leaving bald patches.
Besides these skin issues, there might be symptoms affecting overall health and behaviour. These include:
- Diarrhea
- Irritability
- Fatigue
- Loss of appetite
- Delayed growth
- Anemia
- Absence of menstruation in women
- Mental health issues
- Problems during birth or pregnancy
- Conditions affecting sexual development and function
- Impaired sense of smell and taste
Eye problems might also be noticed, such as inflamed eye-lids, ulcers or opacities in the cornea, and an aversion to light. There may also be immune system abnormalities, which can make the person more susceptible to infections from certain bacteria and yeast. The hallmarks of acrodermatitis enteropathica are hair loss, diarrhea, and a skin rash around the mouth and on the limbs. If it is not treated promptly, the condition can be life-threatening. Other health conditions, such as lack of adequate nutrition, psoriasis, seborrheic dermatitis and glucagonoma syndrome can have similar symptoms to acrodermatitis enteropathica. Some metabolic disorders may also cause a clinical presentation similar to this disease, which is referred to as acrodermatitis dysmetabolic. These disorders can be caused by deficiencies of certain substances such as zinc, amino acids, or biotin.
Testing for Acrodermatitis Enteropathica (Zinc Deficiency)
To confirm a diagnosis, the levels of zinc in the blood are measured. If the fasting measurement is less than 70 micrograms per liter or, for non-fasting individuals, less than 65 micrograms per deciliter, these readings are seen as a key indicator of the condition. But it’s important to carry out these tests with great care to ensure that the readings are correct. Things like using dirty test tubes or needles, or rubber stoppers, can cause falsely high zinc levels. Factors such as stress, inflammation or the time of day can also affect the zinc levels. It is best for the blood sample to be taken in the morning with specially cleaned glass bulbs or tubes.
Having low levels of the protein “albumin” can result in a low zinc level. So it’s good to test for that too. Also, they might measure the levels of the enzyme “alkaline phosphatase”, which relies on zinc, as this can sometimes be useful. If the condition is hard to diagnose, a medical expert may examine the affected skin under a microscope – this isn’t always conclusive but could be helpful. Among the things they’ll be looking out for are specific changes familiar in this condition – these include a build-up of cells causing skin thickening, so-called skin “necrolysis”, which refers to a certain kind of damage in the cell interior, continual skin peeling, a condition causing moist and raw-looking skin, and focal discoloration.
Treatment Options for Acrodermatitis Enteropathica (Zinc Deficiency)
Treatment for this disease usually involves providing the patient with extra zinc, either through their diet (enteral) or through injections (parenteral). The patient might need to take zinc supplements for life, commonly at a dose of 3 milligrams per kilogram of body weight per day. There are many types of zinc supplements available. Zinc sulfate is the preferred supplement taken by mouth, and four milligrams of it contains about one milligram of actual zinc. If zinc needs to be given through injection, zinc chloride is commonly used.
Patients often start to feel better quickly after starting treatment, usually within a few days. The initial sign of improvement is often less irritation, followed by skin improvements.
While undergoing treatment, patients will also need to have regular checks. These consist of measuring zinc levels, full blood counts, checking the size and number of red blood cells (erythrocyte indices), checking the level of copper in the blood and examining the stool for hidden (occult) blood. Blood levels of an enzyme called alkaline phosphate may also rise during treatment with zinc supplements. High levels of zinc in the blood may prevent the absorption of copper, because they both use a common transporter to enter cells; therefore, low copper levels in the blood (hypocupremia) may occur during therapy and should be monitored. Gastric irritation and internal bleeding in the stomach (gastric hemorrhage) could be other side effects of zinc supplementation therapy.
For acquired zinc deficiency, the amount of zinc needed depends on the underlying cause. If a patient has malabsorption, which means their body has trouble absorbing nutrients from food, they may need higher doses of zinc. Simultaneously, applying compresses and skin-softening agents (emollients) to the areas of skin affected can help the skin to heal when used alongside taking zinc supplements.
What else can Acrodermatitis Enteropathica (Zinc Deficiency) be?
The following conditions could be potential reasons for certain skin or dietary problems:
- Zinc deficiency
- Eczema (also known as Atopic dermatitis)
- Shortage of Biotin and other types of enzymes
- Skin yeast infection (Cutaneous candidiasis)
- A lack of proteins in the diet (Dietary iatrogenic deficiency of branched-chain amino acids)
- A rare condition causing blistering of the skin (Epidermolysis bullosa)
- A lack of essential fatty acids in the diet
- HIV
- A genetic disorder that affects the body’s ability to break down certain proteins (Glutaric aciduria type 1)
- A form of malnutrition caused by not getting enough protein (Kwashiorkor)
- A condition related to the body’s processing of the amino acid leucine (Leucinosis)
- Conditions that affect the body’s ability to absorb nutrients from food (Malabsorption syndromes)
- An infection on the oral or throat mucous membranes caused by the Candida fungus (Mucosal candidiasis)
- A rare genetic condition characterized by the body’s inability to break down glycine (Nonketotic hyperglycinemia)
- A common skin condition causing scaly patches, red skin, and stubborn dandruff (Seborrheic dermatitis)
What to expect with Acrodermatitis Enteropathica (Zinc Deficiency)
Providing sufficient zinc supplements can greatly improve outcomes in acrodermatitis enteropathica, with a response rate of 100%. If the condition isn’t treated, it can lead to death within the first few years of life. Complications include slowed growth, skin inflammation, hair loss, and additionally, bacterial and fungal infections which can range in severity.
Possible Complications When Diagnosed with Acrodermatitis Enteropathica (Zinc Deficiency)
Possible Side Effects:
- Secondary infection by bacteria or fungus
- Slowed growth
- Hair loss (alopecia)
- Changes in children’s behaviour
Preventing Acrodermatitis Enteropathica (Zinc Deficiency)
Genetic counseling is highly advised for families that have a history of congenital acrodermatitis enteropathica, a rare genetic disorder. For those who have been diagnosed with this condition, they need to take zinc supplements for life to prevent the symptoms from showing up. Furthermore, it is important for patients to receive consistent education and regular counseling sessions at set times. This ensures they follow their treatment plan closely to manage the condition effectively.
