Beta-propeller protein-associated neurodegeneration (BPAN) is a disorder that damages the nervous system and is progressive, which means that it gradually gets worse. Affected individuals develop a buildup of iron in the brain that can be seen with medical imaging. For this reason, BPAN is classified as a type of disorder called neurodegeneration with brain iron accumulation (NBIA), although the iron accumulation may not occur until late in the disease.

BPAN is caused by variants (also called mutations) in the WDR45 gene. This gene provides instructions for making the WIPI4 protein. WIPI4 has a characteristic structure resembling a seven-bladed propeller, from which the name of the disorder is derived. The WIPI4 protein is involved in a process called autophagy, which helps clear unneeded materials from cells, including excess amounts of an iron storage protein called ferritin.

BPAN is a rare disorder. Its prevalence is unknown, but it is thought to account for between 35 and 40 percent of all cases of NBIA disorders. Some individuals who have been diagnosed with intellectual disability or early-onset parkinsonism based on their signs and symptoms have later been found to have BPAN when genetic testing was done.

This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a variant in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Published Date: March 28, 2022
Published By: National Institutes of Health