Cholesterol Ester Storage Disease Clinical Trial
Official title:
Biomarker for Wolman Disease, AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL
Development of a new MS-based biomarker for the early and sensitive diagnosis of Wolman disease blood (plasma)
Wolman disease (WD) is a rare genetic disorder characterized by complete absence of an enzyme known as lysosomal acid lipase (LIPA). This enzyme is required to breakdown (metabolize) lipids in the body. Without the LIPA enzyme, lipids may abnormally accumulate in the tissues and organs of the body causing a variety of symptoms. WD is the most severe expression of LIPA deficiency. Milder form of the disorder are known as cholesteryl ester storage deficiency. The symptoms of WD usually become apparent shortly after birth, usually during the first few weeks of life. Affected infants may develop bloating or abdominal distention and may have significant hepatosplenomegaly. Fibrosis of the liver may also occur. In some cases, fluid may accumulate in the abdominal cavity (ascites). Infants with WD have serious digestive abnormalities including malabsorption, a condition in which the intestines fail to absorb nutrients and calories from food. Malabsorption associated with WD causes persistent and often forceful vomiting, frequent diarrhea, foul-smelling, fatty stools (steatorrhea) and malnutrition. Because of these digestive complications, affected infants usually fail to grow and gain weight at the expected rate for their age and sex (failure to thrive). Hepatosplenomegaly and protrusion of the abdomen can cause umbilical hernia, a condition in which the contents of the stomach may push through an abnormal opening or tear in the abdominal wall near the bellybutton. Additional symptoms may also occur in WD including yellowing of the skin, mucous membranes and whites of the eyes (jaundice), a persistent low-grade fever, and poor muscle tone (hypotonia). Infants may exhibit delays in the development of motor skills. A distinct finding associated with WD is the hardening of adrenal gland tissue due to the accumulation of calcium (calcification). The adrenal glands are located on top of the kidneys and produce epinephrine and norepinephrine. Other hormones produced by the adrenal glands help to regulate the fluid and electrolyte balance in the body. Calcification of the adrenal glands is not detectable by physical examination, but can be seen with x-ray study. Calcification may prevent the adrenal glands from producing enough essential hormones and can affect metabolism, blood pressure, the immune system and other vital processes of the body. Infants with WD may experience the loss of previously acquired skills required the coordination of muscle and motor skills (psychomotor regression). The symptoms of WD often get progressively worse eventually leading to life-threatening complications during infancy including extremely low levels of circulating red blood cells (severe anemia), hepatic dysfunction or failure, and physical wasting away and severe weakness often associated with chronic disease and marked by weight loss and loss of muscle mass (cachexia or inanition). WD is caused by mutations of the lysosomal acid lipase (LIPA) gene. It is inherited as an autosomal recessive trait. More than 50 cases have been reported in the medical literature. However, cases may go undiagnosed or misdiagnosed making it difficult to determine the disorder's true frequency in the general population. New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to identify and validate a new biochemical marker from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment. ;
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