What Is GRACILE Syndrome?

The GRACILE syndrome is caused by genetic mutations in the BCS1L gene. The BCS1L gene instructs mitochondria to produce energy from food to be used for vital functions of cells.

The genetic changes make the abnormal protein break faster than healthy protein. A minimal number of healthy proteins remain, which form into complete complex III, especially in the liver and kidneys.

A decreased complex III activity and oxidative phosphorylation interfere with energy production. Without energy, the organs get damaged, resulting in the features of the GRACILE syndrome.

GRACILE syndrome is inherited in the autosomal recessive pattern. The parents of autosomal recessive carry one copy of the mutated gene but do not show any signs or symptoms.

The signs and symptoms of the GRACILE syndrome include:

• Abnormal gestation growth or slow intrauterine growth; the baby is born smaller than usual.
• An increased concentration of amino acids in the urine of the child.
• Growth delay or growth retardation is the characteristic feature of the GRACILE syndrome. The average birth weight of affected infants is only 1700 grams.
• The child's physical growth is below normal.
• Impaired flow of bile due to bile duct blockage.
• The body fails to metabolize the iron properly, resulting in increased levels of iron in the body, particularly in the liver.
• Cirrhosis of the liver. Scarred liver tissues replace regenerative nodules and fibrotic tissues, which results in poor liver function.
• Most of the affected infants do not survive for longer periods. Most children cannot survive beyond four months.

Diagnosing this condition is challenging for clinicians due to the limited information available. The healthcare provider asks for the symptoms.

Depending on the symptoms, the following are done:

• Check for body vitals, such as temperature, heart rate, breathing rate, blood pressure, weight, and height
• Check for any pain, tenderness, lumps, masses, swelling, or other changes
• Check the heart, lung, or function of abdominal organs
• Tap certain areas of the body to check for the presence of fluid, air, or solid structures
• Evaluate the nervous system by checking nerve coordination, reflexes, sensory, and motor function
• Assess the strength and balance
• Genetic testing is done

Laboratory tests findings for the GRACILE syndrome are:

• Lactic acidosis
• Elevated hepatic iron concentration
• Decreased transferrin saturation
• Increased circulating ferritin saturation

There is no cure for the GRACILE syndrome. Symptomatic treatment is usually done. Infants with GRACILE syndrome need intensive care, alkali therapy, and supplementation of urine losses. 

The experimental treatments include reducing the level of acids and iron in the blood. However, this does not extend the infant's lifespan.

The prognosis is quite poor. Half of the infants die within a few days after birth. Even with the best possible treatments available, all infants with the GRACILE syndrome cannot survive past four months after birth.