Sjögren–Larsson syndrome

Not to be confused with Sjögren's syndrome, an autoimmune disorder which can cause many problems including dry skin.

Alternate names

SLS; Fatty aldehyde dehydrogenase deficiency; FALDH deficiency; FADH deficiency; FAO deficiency; Sjögren-Larsson syndrome; Sjogren Larsson syndrome; Ichthyosis, spastic neurologic disorder, and oligophrenia

Definition

Sjogren-Larsson syndrome (SLS) is an inborn error of lipid metabolism, characterized by congenital ichthyosis (dry, scaly skin), intellectual disability, and spasticity (stiffness and involuntary muscle spasms).

Cause

• SLS is caused mutations in the FADH (fatty aldehyde dehydrogenase) gene, which is located on chromosome 17 on the p arm at band 11.2.
• The enzyme made by the FADH gene is responsible for breaking down certain molecules called medium- and long-chain fatty aldehydes.

Gene mutations

• If FADH is not functioning properly, these and related molecules build up in the body, specifically the membranes of the skin and brain, leading to the symptoms associated with SLS.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive fashion.

Onset

The signs and symptoms of SLS typically occur within the first two years of life.

Signs and symptoms

A primary feature of SLS is dry, scaly skin, which is called ichthyosis.

In addition to ichthyosis, people can develop some or all of the following symptomsː

• Developmental delay
• Intellectual disability
• Speech difficulties
• Seizures
• Spastic diplegia/tetraplegia paralysis (diplegia is paralysis of both legs; tetraplegia is paralysis of all four limbs)
• Spasticity in the legs: leg spasms, which can impair motor abilities and waking
• Glistening white dots in the retina of the eye
• Pruritus (itching)
• Preterm birth

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal pyramidal sign
• Dry skin
• Erythema
• Hyperkeratosis
• Ichthyosis
• Intellectual disability(Mental deficiency)
• Kyphosis(Hunched back)
• Skeletal dysplasia
• Spastic diplegia

30%-79% of people have these symptoms

• Abnormality of retinal pigmentation
• Corneal erosion(Damage to outer layer of the cornea of the eye)
• Dysarthria(Difficulty articulating speech)
• Generalized hyperpigmentation
• Inflammatory abnormality of the eye
• Macular degeneration
• Myopia(Close sighted)
• Photophobia(Extreme sensitivity of the eyes to light)
• Retinopathy(Noninflammatory retina disease)
• Seizure

5%-29% of people have these symptoms

• Abnormality of dental enamel(Abnormal tooth enamel)
• Joint stiffness(Stiff joint)
• Microcephaly(Abnormally small skull)
• Muscular hypotonia(Low or weak muscle tone)
• Scoliosis
• Short stature(Decreased body height)
• Urticaria(Hives)

Diagnosis

• SLS can be diagnosed by a biochemical blood test that determines if FADH activity is normal.
• In addition, because mutations in FADH are known to cause SLS, the gene can be sequenced in order to determine if any mutations are present.
• This also provides the option of genetic and prenatal testing, which can allow parents to make informed decisions about having children.

Treatment

• Topical application of various agents have been used to treat the ichthyosis.
• Some clinical studies have found that a drug called zileuton can be beneficial in the treatment of SLS.
• In these studies, the drug successfully reduced the severity of the pruritis (itching), and improved the behavior of the treated child. While this drug does not cure SLS, it has the potential to greatly improve the quality of life of children with SLS.
• Seizures usually respond well to anti-convulsant medications and spasticity is improved with surgery.
• Diets supplemented with medium-chain fatty acids have been reported to improve the skin, but the results are inconsistent.