Wilson's Disease Case Sharing: Carrier Screening and PGT-M

The British media reported a couple having a child with green eyes, a trait that was absent in both families, and DNA testing unexpectedly revealed a secret of infidelity among the older generations, confirming the child's green eyes were hereditary. Green eyes, from a genetic standpoint, may be both a beautiful gift from God and an indication of the rare "Wilson's disease."

Lee Women's Hospital recently performed carrier screening on a woman preparing for pregnancy and discovered a positive result, recommending that her husband also undergo carrier screening. If both partners are carriers, they should consider using "Preimplantation Genetic Testing for Monogenic Disorders (PGT-M)" during IVF to prevent congenital diseases from being passed down to the next generation.



Currently, there are over 700 patients with this disease in Taiwan, and the number of carriers is estimated to exceed 250,000. "Wilson's disease" can produce brown-green rings on the cornea and affect the liver, kidneys, central nervous system, and other organs in the body. It can also cause psychiatric symptoms resembling Parkinson's disease, and in female patients, it may lead to infertility and miscarriages.
 

Carrier screening for a woman and found she carries the "Wilson's disease" gene

Miss Lee, a 28-year-old woman from Changhua, recently sought treatment at Lee Women's Hospital. She asked to be screened for "Wilson's disease" carriers because she had a family history of the disease. She wanted to make sure she didn't have this gene before getting pregnant in order to avoid having a child with this rare disorder. Unfortunately, the carrier test result revealed that she carries the "Wilson's disease" gene. As a result, our Ob-Gyn recommended that her husband also undergo carrier screening to determine the likelihood of the child developing the disease. 

If a woman becomes pregnant naturally and is unaware of her carrier status, there is no need to panic. She can undergo amniocentesis around 16 weeks of pregnancy to determine if the fetus is affected and discuss further treatment with the obstetrician.
 

PGT-M can prevent the birth of rare disease-affected children

"Wilson's disease" has an autosomal recessive inheritance pattern. If one partner is a carrier and the other is normal, their children have a 50% chance of being carriers and 50% chance of being normal. If both parents are carriers, their children have a 25% chance of developing the disease, a 50% chance of being carriers, and a 25% chance of being normal. 

Prof. Li Yueh-Chun, head of the Genetic Laboratory, emphasized that carriers of recessive genetic diseases do not develop the disease nor show any clinical symptoms, making it easy to overlook. However, it is important to be mindful of the carrier status of the partner during family planning. Carrier screening can be used to ensure the genetic status of the next generation, and if there is a family history, couples preparing for pregnancy must undergo carrier screening. In the event of a positive carrier result, advanced PGT-M can be utilized during IVF to analyze the number of chromosomes and gene types of 5 to 10 trophectoderm cells taken from the embryo. This allows identification of embryos without hereditary diseases and prevents the transmission of genetic disorders to the next generation.
 

More than 700 patients with Wilson's disease in Taiwan and female patients may experience infertility or miscarriages

Prof. Li Yueh-Chun explained that "Wilson's disease" is caused by a mutation in the ATP7B gene on the 13th pair of chromosomes. This leads to abnormal copper metabolism in the body, resulting in copper accumulation in the cornea, forming "Kayser-Fleischer rings," which make patients appear as if they have green eye color. However, not every patient exhibits this symptom. Copper can also accumulate in the liver, kidneys, central nervous system, and other organs, leading to conditions such as depression and psychiatric symptoms resembling Parkinson's disease. Female patients may experience irregular menstrual cycles, amenorrhea, infertility, or miscarriages, making it a challenging and rare disease to manage.

Currently, the prevalence of "Wilson's disease" is approximately 1 in 30,000, with a carrier rate of about 1.1%, estimating the number of carriers to exceed 250,000 people in Taiwan. According to statistics from Taiwan Ministry of Health and Welfare, there have been 701 reported cases of this rare disease as of 2022. 

Due to the diverse clinical manifestations of this rare disease, it is not easily detected in the early stages. While only a few patients exhibit symptoms in childhood, most develop the disease in adulthood when copper has accumulated to a certain level. Some individuals may only show abnormal clinical signs in the liver or kidneys, making it difficult to identify "Wilson's disease" during the initial medical visit. However, this disease can affect multiple organs throughout the body, requiring treatment from various specialties. The treatment process is time-consuming and incurs high medication costs. Although there is partial insurance coverage, it still results in a significant financial burden for patients.