BCS1L-related disorders

What Are BCS1L-Related Disorders?

BCS1L-related disorders are a group of autosomal recessive disorders caused by mutations in the BCS1L gene. This gene is important for the energy-generating structures (mitochondria) in our cells to work properly. Since many cells in different parts of the body need energy to work properly, individuals with BCS1L-related disorders may have problems in many different parts of the body. BCS1L-related disorders are comprised of three different conditions described below.

GRACILE Syndrome

GRACILE syndrome is the most severe of the BCS1L-related disorders. “GRACILE” is an acronym which stands for the disease's main symptoms:

Growth retardation - Newborns have trouble growing and are usually smaller than average.

Aminoaciduria - There are increased levels of amino acids in the urine.

Cholestasis - Newborns have trouble making digestive fluid (bile) or transporting it to the right place, which can lead to liver damage.

Iron overload - The body is unable to break down iron properly leading to high levels of iron in the liver.

Lactic acidosis - There is too much lactic acid in the blood.

Early death - Newborns with GRACILE syndrome usually pass away within the first few months of life.

Complex III Deficiency

Complex III deficiency can be relatively mild or can cause death in childhood. Individuals with complex III deficiency often feel weak and tired and can sometimes have problems with their liver, kidney, and brain. If the brain is affected, there can be issues with learning, movement, and muscle weakness. Some patients may also have a defect in their heart muscles (cardiomyopathy) which can cause heart failure. Hearing impairment or deafness can occur. Individuals with complex III deficiency can also have high levels of lactic acid (lactic acidosis), ketones (ketoacidosis), or sugar (hyperglycemia).

Björnstad Syndrome

Björnstad syndrome is characterized by hearing loss (sensorineural deafness) and dry, brittle hair (pili torti). Children with Björnstad syndrome usually have mild to severe hearing loss within the first two years of life. There can be hair loss (alopecia) due to their abnormally fragile hair, usually on the head, eyebrows, and eyelashes. Björnstad syndrome is the mildest BCS1L-related disorder.

How Common Are BCS1L-Related Disorders?

The prevalence of GRACILE syndrome is approximately 1 in 47,000 babies in Finland. GRACILE syndrome is very rare outside of Finland.

The prevalence of complex III deficiency is unknown.

Björnstad syndrome is estimated to affect 1 in 1,000,000 individuals in the world.

How Are BCS1L-Related Disorders Treated?

Most treatments for GRACILE syndrome are aimed at making infants comfortable until they pass away. There is no known treatment for GRACILE syndrome that extends lifespan.

Complex III deficiency syndrome treatment generally focuses on managing symptoms and slowing down the progression of the disease. There is no cure for complex III deficiency.

Individuals with Björnstad syndrome may use hearing aids or cochlear implants to improve their hearing. Otherwise, Björnstad syndrome does not usually require medical treatment.

What Is the Prognosis for Individuals with a BCS1L-Related Disorder?

Even with the best possible treatment, most babies with GRACILE syndrome will die within four months of birth.

Severe cases of complex III deficiency can be fatal in childhood while individuals with milder symptoms of complex III deficiency can survive into adolescence or adulthood.

Björnstad syndrome usually does not affect lifespan.