"Conducting genetic testing on family members and related families when a baby is found to be a carrier from a newborn screening test can identify more individuals with carriers. For rare diseases, such as Gaucher's disease, early diagnosis improves the patient's quality of life and saves the societal cost."

Starting this year, the items for the newborn screening test, which is conducted in newborns within 48-72 hours of birth regardless of any symptoms shown, has expanded. As a result, early diagnosis of rare diseases is more likely.

For example, reimbursable items now include Lysosome storage disorder (LSD). Many hope that circumstances surrounding the treatment of diseases with a 'diagnostic odyssey,' like Gaucher's disease and Fabry's disease, will improve.

Daily Pharm met with Beom Hee Lee, a Professor of the Department of Pediatrics at Asan Medical Center's Medical Genetics Center, to discuss the significance of newborn screening testing and treatment options.

LSD is estimated to occur in 1 in 7,000 to 9,000 people. There are approximately 50 known LSDs, depending on specific enzyme deficiencies. Among these, six LSDs, including Pompe disease, mucopolysaccharidosis (Type 1·2), Gaucher's disease, and Fabry's disease, have treatments and are manageable.

"LSD is a disease in which lysosomal degrading enzyme, which eliminates unwanted materials within the cell, is genetically deficient. Most prominent diseases include Gaucher's disease, Fabry's disease, and Pompe disease," said Lee, adding, "However, the causes and symptoms are disease-specific. For example, in Gaucher's disease, the risk of leukemia increases, and neurological symptoms are life-threatening."

The government's decision to include LSD in reimbursable items for newborn screening tests this year is crucial because it could lead to early diagnosis and early treatment.

Approximately 70 patients are being treated for Gaucher's disease, one of LSDs, in South Korea. Because there are only a few patients in South Asia, it is difficult to assess the prevalence rate.

Gaucher's disease is also a rare disease with the 'diagnostic odyssey,' taking around 13 years on average to diagnose. Lee said that the expanded reimbursement scope of the screening test is expected to be beneficial.

"Patients often visit several hospitals until getting diagnosed because rare diseases are not acknowledged well and there are only a few doctors with specialties," Lee said, adding, "There are cases of patients diagnosed with Gaucher's disease in their last years, and a teen patient was diagnosed with Gaucher's disease with hepatosplenomegaly after 10-years of testing despite reduced platelet levels."

"As six types of enzyme activity tests have been included in reimbursable items of newborn screening test, starting January 2024, potential for diagnosing Gaucher's disease has opened up," Lee said, adding, "It provides patient access and advantages for reducing complications by early disease diagnosis and treatment, suggesting that circumstances for treatment are improving."

Lee explained that six months had passed since the testing was implemented, and no patients were reported to have abnormal findings diagnosed with Gaucher's disease. However, a positive effect is expected because the testing could expand the genetic disease LSD diagnosis to family members and related families.

Gaucher disease requires early diagnosis and early treatment…unmet needs for treating neurological symptoms

The standard therapy for Gaucher's disease involves receiving a bi-weekly intravenous injection of a deficient enzyme protein as part of an enzyme replacement therapy (ERT).

Lee believes that different ERTs yield similar treatment effects. Since the treatment effects and safety profile have been confirmed, ERT may effectively lessen liver and spleen enlargement.

"Neurological symptoms of Gaucher's disease occur regardless of age, typically found in infancy, teenage years, and early-20s, despite different timing of neurological symptom occurrence and diagnosis," Lee said, adding, "Even the patients who have improved symptoms with ERT can experience sudden neurological symptoms, significantly burdening patients and caregivers."

Although there are no treatment options for effectively managing neurological symptoms, studies are being conducted with chaperone therapy using ambroxol.

Ambroxol is an active ingredient used for treating respiratory diseases. In a study of ambroxol in combination with ERT, it has been reported to reduce the number of seizures and alleviate or prevent symptom worsening after around 10 years of treatment in patients with Gaucher's disease who have neurological symptoms.

"Although many patients have improved neurological symptoms using ERTs, patients had the inconvenience of having to take many pills in a day. Moreover, ambroxol is not officially approved," Lee said, adding, "A treatment development is needed to fulfill unmet patient medical needs for effective neurological symptoms."

Despite receiving positive review for newborn screening test, a concern for increased screening cost arises

Lee expected that discussions about potential unnecessary screening increases due to the expanded scope of the newborn screening test might be needed.

"When tests are being done in a broad term, an initial purpose for conducting screening may not be achieved and it may result in unwanted outcomes," Lee said, adding, "Caregivers tend to independently receive genetic testing with low accuracy in addition to the government-funded tests. As a result, the cost of conducting tests with out-of-pocket fees may be a burden."

Some diseases may require immediate treatments upon the identification of a carrier. However, several diseases, within the six types of LSD testing category, do not require immediate treatment.

"Testing with fees conducted in newborns may not be for diseases that must be identified at the newborn stage, and the rate of the diagnosis for certain disease at further tests are low," Lee mentioned, "It is a common issue that nations conducting similar screening program face."

Regarding this issue, Lee emphasized the importance of accurate final diagnosis and treatment through enzyme analysis testing or genetic testing rather than excessive analysis at the screening stage.

"For Gaucher's disease, treatments are available, and patients can maintain typical lifestyles if treated and managed well. It does not affect marriage or daily lives," Lee said, "The most crucial factor is early diagnosis and early treatment. Because Gaucher's disease can cause irreversible damages to the body, treatment must begin before symptom manifests."