Biomarker for Wolman Disease (BioWolman)
Biomarker for Wolman Disease (BioWolman)
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.
Inclusion Criteria:

 -  Informed consent will be obtained from the parents before any study related
 procedures.

 -  Patients of both gender older than 2 month

 -  The patient has a diagnosis of Wolman disease or a high-grade suspicion for Wolman
 disease

 High-grade suspicion present, if one or more inclusion criteria are valid:

 -  Positive family anamnesis for Wolman disease

 -  Vomiting, diarrhea

 -  Malnourishment, difficulty growing and gaining weight

 -  Enlarged liver and spleen (hepatosplenomegaly), which causes a distended abdomen

 -  Low muscle tone (hypotonia)

 -  Anemia

 -  x-ray reveals calcified adrenal glands

 Exclusion Criteria:

 -  No Informed consent from the parents before any study related procedures.

 -  Patients of both gender younger than 2 month

 -  No diagnosis of Wolman disease or no valid criteria for profound suspicion of Wolman
 disease