Sjogren-Larsson Syndrome - A Broadview

Introduction:

Swedish physicians Sjogren and Larsson described the Sjogren-Larsson syndrome, or SLS, in 1957, and the prevalence of this condition is one per 250,000 individuals. They proposed that Swedes born with this condition have all descended from a common ancestor. This condition is visible from the time a child is born. Other names given to this syndrome are ichthyosis oligophrenia syndrome, Fatty Aldehyde Dehydrogenase (FALDH) deficiency, and spastic neurologic disorder. Sjogren-Larsson syndrome is often confused with Sjogren syndrome, which has similar names, but it should be noted that Sjogren syndrome is an autoimmune disease. In contrast, the topic discussed here, Sjogren-Larsson syndrome, is an autosomal recessive syndrome.

What Is Sjogren-Larsson Syndrome?

It is an inherited genetic disorder that affects infants, especially those who are born prematurely. The affected individual usually has scaling skin (ichthyosis). The infant has mild symptoms after birth and gradually worsens later in infancy. Along with dry and scaly skin, it also leads to neurological and eye disorders that appear in early childhood. Skin abnormalities are spread over the whole body, and only the skin of the face is not involved.

What Causes Sjogren-Larsson Syndrome?

The Sjogren-Larsson syndrome occurs due to a deficiency of a particular enzyme, fatty aldehyde dehydrogenase, or gene mutation, the ALDH3A2 gene. Genes are the basic functional unit of heredity, made up of DNA (deoxyribonucleic acid).

ALDH3A2 Gene Mutation: The ALDH3A2 is a member of the aldehyde dehydrogenase gene family that provides instructions for producing the Fatty Aldehyde Dehydrogenase (FALDH) enzyme. The FALDH enzyme helps break down fats and molecules (fatty aldehydes to fatty acids). This breakdown process of molecules is a part of fatty acid oxidation, where it is converted into energy. These enzymes are present in tissues, the liver, and cells (endoplasmic reticulum that transports and processes protein). Around 80 ALDH3A2 gene mutations lead to Sjogren-Larsson syndrome. When the gene mutation occurs, the FALDH enzyme cannot break down the fatty aldehyde molecules, and those fats build up in the cells. In tissues, when the fat deposits, it adheres to the body's normal cells.

SLS is an autosomal recessive condition, meaning that when a genetic disorder like SLS occurs, two copies of the gene are acquired, one from each parent. If the individual acquires two defective genes, then a recessive genetic disorder occurs, and when an individual acquires one normal and one defective gene, that person is the carrier. The risk of a carrier transferring the defective gene to a child is 25 percent with each pregnancy.

What Are the Symptoms of Sjogren-Larsson Syndrome?

Symptoms of SLS start within the first two years of life and preterm birth. Some of the most common visible symptoms include the following:

• Dry and scaly skin (ichthyosis).

• At birth, the skin is red (erythema) and has a scaly brown-yellowish tone later in infancy.

• Muscle stiffness.

• Delayed development of motor skills.

• Wide space between the teeth or eyes.

• Uncontrolled eye movements.

• The thick scales of the skin spread around the neck, underarms, groin, and lower abdomen.

• Seizures.

• Spinal abnormalities.

• Smaller head.

• Numbness in hands and feet.

• Difficulty in speaking.

What Are the Different Modalities Through Which Sjogren-Larsson Syndrome Is Diagnosed?

The symptoms are most visible by age three and can be diagnosed by thorough clinical examination. To confirm, there are two ways to diagnose Sjogren-Larsson syndrome. They are as follows:

1. Blood Test - A blood test determines the levels and activity of fatty aldehyde dehydrogenase enzymes. A healthcare expert will take the blood from the arm’s vein by inserting a fine needle. A small amount of blood is drawn out, and the sample is sent to a laboratory for further testing.

2. Genetic Testing - It examines the DNA, a database that carries instructions for the body’s functions. A genetic test is done to check the ALDH3A2 mutation. It is always informed before genetic testing that, in some cases, the negative result does not confirm the diagnosis, and the test can be performed again. The blood test is done by a healthcare expert who takes the blood from the arm’s vein, and the sample is sent to the laboratory for further testing.

How Is Sjogren-Larsson Syndrome Treated?

There is no cure for Sjogren-Larsson syndrome, so the focus is to treat the symptoms.

• To improve the skin's condition, a diet low in long-chain fats (nuts, avocado, and fish) is advised to switch to medium-chain fats (coconut oil and dairy products).

• Physical therapy can be done to help with muscle stiffness, as the professional will help in stretching and the movement of the muscles through various activities.

• Speech and language therapy can help kids with trouble speaking and communicating with others.

• Anticonvulsants or anti-seizure drugs such as Paraldehydes are given to control seizures.

• Applying urea-containing or keratolytic ointments also helps reduce the skin's scaling. It should be applied twice or thrice a day per the doctor’s advice and should not be used if it is not suggested by the professional, as the medication may have certain side effects.

• Genetic counseling is given to the patient’s family to make them understand the severity of the syndrome, how it can still be passed on to the next generation, and how to overcome the fear of the condition. This counseling helps women who are thinking of conceiving or are pregnant so that they understand the situation beforehand only.

What Is the Life Expectancy of an Individual With Sjogren-Larsson Syndrome?

Most people affected by Sjogren-Larsson syndrome syndrome experience dry eyes and dry mouth. General health and life expectancy are usually unexpected.

Conclusion:

Sjogren-Larsson syndrome is a genetic disorder that can affect an individual from birth. It is a genetic condition passed on by a mother, father, or sometimes both. The symptoms of SLS are visible from an early age, which makes it easy to diagnose. A blood test helps detect the genetic mutation that leads to this condition. SLS sounds like a scary disease, but if diagnosed on time, it can help control the symptoms that affect the normal day-to-day life of an individual. Along with that, genetic counseling will help the whole family understand the SLS more clearly.