The Rare
Diseases

Bile acid synthesis disorders (BASDs) are a group of rare, inherited metabolic disorders caused by defects in the enzymes that are involved in making bile acids. Bile acids promote the flow and excretion of bile, excess cholesterol and waste, and help the intestines absorb fat and fat-soluble vitamins.

When the body is unable to produce normal bile acids, it can result in interrupted bile flow (cholestasis), often resulting in malabsorption of vital nutrients and the buildup of toxic materials in the body. BASDs are typically detected during infancy.

If left untreated, buildup of toxic materials may result in progressive liver disease.

People with cholestasis may have yellowing of the skin and eyes, failure to thrive and growth deficiency. Cholestasis may be accompanied by diarrhea, and pale, clay-colored stools caused by lack of bile. Other signs may include weakened bones caused by vitamin D deficiency, easy bleeding and bruising due to blood clotting issues from vitamin K deficiency, and vision problems due to vitamin A deficiency.

Yellow skin
or eyes (jaundice)

Fractures

Easy Bleeding
and Bruising

Growth Deficiency

Peroxisomes are important parts of each cell in the body and are necessary for cell function, and for breaking down fats and chemicals, and getting rid of waste in the cells. In people with peroxisome biogenesis disorder-Zellweger spectrum disorder (PBD-ZSD), more commonly referred to as Zellweger spectrum disorder or ZSD, alterations in one of the PEX genes lead to a loss of peroxisome function. Loss of peroxisome function can affect all major organ systems in the body.

Until recently, PBD-ZSD was viewed as three separate diseases, but we now know that PBD-ZSD is a set of disorders that form a spectrum of disease. This spectrum can range from mild (infantile Refsum disease), to moderate (neonatal adrenoleukodystrophy), to severe (Zellweger syndrome).

PBD-ZSD is estimated to occur in 1 in 50,000-70,000 births in the United States. It is inherited in an autosomal recessive pattern, meaning that a child is affected when each parent passes on one copy of the mutated gene.

People with PBD-ZSD may experience multisystem complications including neurological problems and seizures, delayed growth and development, hearing and vision loss, poor muscle tone, and skeletal and dental abnormalities. PBD-ZSD affects each person differently. How the disease impacts someone can vary with the age at which their symptoms first start to appear, the number of functioning peroxisomes they have, and the rate at which the disease progresses.

Individuals with Zellweger syndrome, at the severe end of the spectrum, develop signs and symptoms of the condition as newborns. These infants typically experience weak muscle tone (hypotonia), feeding problems, hearing and vision loss, liver dysfunction and seizures. Survival is usually not beyond the first year of life.

Individuals on the less-severe end of the spectrum may have hypotonia, vision problems, hearing loss, liver and kidney dysfunction, decreased bone mineral density developmental delay, and some degree of intellectual disability.

Weak Muscle Tone (Hypotonia)

Feeding Problems

Hearing and Vision Loss

Liver Dysfunction

Seizures

Smith-Lemli-Opitz Syndrome (SLOS) is a rare, genetic condition caused by a mutation in the 7-dehydrocholesterol reductase (DHCR7) gene that helps the body to produce cholesterol. Patients with SLOS are unable to make sufficient amounts of cholesterol, an essential nutrient for proper growth and development. Because cholesterol is also necessary for production of bile acids in the liver, it is likely that low cholesterol levels in SLOS impair bile acids from being made.

Bile acids help digest dietary cholesterol from the intestine. Low bile acid levels likely prevent dietary cholesterol from being absorbed properly and contribute to the cholesterol deficiency seen in SLOS.

SLOS occurs in about 1 of every 20,000 live births.

In addition to low cholesterol absorption that can delay growth and development, some patients may experience elevated or abnormal liver function levels, such as AST and ALT, which are important measurements of liver health.

Decreased Cholesterol Synthesis/Production

Delayed Growth and Development

Elevated or Abnormal Liver Function