KATHMANDU, FEBRUARY 27

Hari Bahadur (name changed) was immensely joyful upon the birth of his son, only to be plunged into despair when the infant was diagnosed with Niemann-Pick disease (NPD) Type B, a rare genetic condition, after nine months.

Hari Bahadur took his son to a nearby provincial hospital where doctors treated the baby for pneumonia. Despite their efforts, the infant's condition worsened, prompting a referral to Kathmandu for further evaluation and treatment.

At Kanti Children's Hospital, the premier pediatric facility in Nepal, doctors made valiant efforts to treat pneumonia afflicting his son, but their endeavors proved futile.

As seven months elapsed, the prolonged illness imposed significant financial strain and stress upon Hari Bahadur, who earned his livelihood through a seasonal job in a district bordering India. In light of the persistent challenges, doctors eventually recommended seeking treatment in New Delhi.

Accordingly, he sought medical assistance at Sir Gangaram Hospital, where doctors recommended a DNA test. Three months later, the results confirmed Niemann-Pick disease (NPD) Type B.

In a distressing turn of events, Hari Bahadur found himself in a desperate situation when access to essential medication for his son was limited in Delhi, the Indian capital.

Of late, more cases of rare genetic conditions are coming out in the medical resource-poor Nepal, leaving dozens of patients and their families in distress. Bureaucratic and logistic difficulties in importing essential drugs to the country have added to the trouble, and experts and stakeholders say the government must take initiatives to address the issue.

Hari Bahadur's hardship: A case in point

Determined to find a solution, Hari Bahadur turned to the renowned All India Institute of Medical Sciences (AIIMS) for assistance. However, to his dismay, Nepali citizens were denied access to the medication they desperately needed.

As eighteen months passed with little progress, the doctor at AIIMS finally made a referral to Dr. Rupesh Mishra, a clinical geneticist at Civil Service Hospital in Kathmandu. Hari Bahadur hoped Dr. Mishra would facilitate the procurement of the necessary medicine, manufactured by Sanofi, from Nepal.

However, individual importation of the drug proved impractical. When approaching Yeti Distributors for assistance, Hari Bahadur faced insurmountable customs duties of approximately Rs1.5 million, beyond his reach.

Hari Bahadur implored the government to provide access to orphan drugs or facilitate their availability to ensure the survival of his son and others facing similar genetic disorders across the nation.

The severity of rare genetic conditions

In a recent announcement, the World Health Organization (WHO) delineated rare diseases as conditions affecting a small fraction of the population, specifically fewer than 1 in 2,000 individuals within a given populace.

Despite their rarity, the cumulative impact of rare diseases is far-reaching, affecting over 300 million people globally across more than 7,000 distinct conditions. Within the European Union (EU) alone, rare diseases afflict approximately 30 million individuals.

Amidst global recognition of the challenges faced by those grappling with rare diseases, the United Nations (UN) took a significant step forward in December 2021. With the passage of a resolution titled 'Leave No One Behind', the UN underscored its commitment to supporting families contending with rare diseases, championing inclusivity within societies worldwide.

This mission aligns closely with the overarching goals outlined in the Sustainable Development Goals (SDGs), which emphasize the creation of equitable and inclusive communities.

WHO Director-General Dr. Tedros Adhanom Ghebreyesus reaffirmed the vision embedded within the SDGs-a world where no one is marginalized, including individuals grappling with rare diseases. This declaration underscores the importance of global cooperation and solidarity in addressing the diverse healthcare needs of all individuals, regardless of the rarity of their condition.

Dr. Rupesh Mishra, a genetic specialist at Civil Service Hospital in Kathmandu, reveals that Nepal has identified over 50 distinct cases of rare diseases, encompassing conditions such as Gaucher disease, Niemann-Pick disease, Ehlers-Danlos syndrome, Neurofibromatosis, Marfan syndrome, Duchenne muscular dystrophy, spinal muscular atrophy (SMA), Prader-Willi syndrome (PWS), Angelman syndrome, numerous chromosomal abnormalities, and others, thus far.

Dr. Mishra further says there is a need for enhanced healthcare infrastructure and support services to address the complex needs of individuals affected by rare diseases within Nepal and beyond.

Clinical experience in Nepal

But it often takes years to identify such conditions due to a lack of understanding in Nepal, says Dr. Rajan Pandey, a senior physician at Nepalgunj-based Bheri Regional Hospital.

Dr. Pandey notes that sickle cell and thalassemia are prevalent in certain communities in the region. Additionally, other conditions such as hemoglobin E, thalassemia alpha, G6PD deficiency, and periodic paralysis are also common in the area.

He further explains that 80 percent of the conditions observed are genetic disorders while the remaining cases involve autoimmune diseases, rare cancers, metabolic disorders, and immune-related conditions.

Patients and their relatives often find themselves isolated from social, economic, and emotional support due to prevailing conditions. 'It's high time that their mental health issues were taken very seriously,' Dr. Pandey shares.

Coinciding with Dr. Pandey's remarks, Hari Bahadur laments, 'Fearing social exclusion, we have not openly disclosed our case to society, nor have we been able to seek assistance from the local or provincial level government.'

Referring to the mental health issues of patients, Dr. Mishra, also a member of the Mental Health for Wellbeing team for rare diseases at Pasis-based Eurodis organization, says, 'Psychiatric counseling should be provided to patients and their relatives simultaneously to keep them mentally fit.'

Likewise, Dr. Niraj Parajuli, a senior consultant dermatologist at Bir Hospital, underscores the significance of genetic factors in rare skin diseases. He also highlights a data gap in Nepal due to inadequate recording systems, leading to diagnosis delays and financial strain for patients.

'Conditions such as xeroderma pigmentosa, epidermolysis bullosa, and albinism have genetic origins, while pemphigus is autoimmune, and mycetoma arises from prevalent infections have been diagnosed in Nepal' says Dr. Parajuli, advocating for awareness campaigns and accessible testing but acknowledges challenges in cost and treatment.

Hari Bahadur states that at least Rs 2.5 million is required to treat his son. Without government support, it's a herculean task, beyond his reach.

Prabha KC, a founding member and assistant in-charge at the Muscular Dystrophy Foundation-Nepal (MDF-Nepal), states, 'We currently serve approximately 1,000 patients afflicted with genetic disorders, with 60 percent suffering from Duchenne disorder. We offer them a day-care facility where they undergo rehabilitation.'

'Despite facing financial hardships, we strive to deliver improved services to our patients.' KC expressed lamentation over 'our dependency on local donors as well as foreign donors to sustain our organization.'

Furthermore, she highlights the lack of genetic testing facilities in the country, which compels patients to send their samples abroad at a high cost.

Diagnostic procedure

Patients often face challenges accessing advanced genetic disorder testing due to a lack of well-equipped laboratories, forcing them to send samples abroad at high costs, according to medical experts.

Dr. Surabhi Aryal, a pediatrician and clinical geneticist serving as an assistant professor in the Department of Pediatrics at the Institute of Medicine Teaching Hospital in Kathmandu, states, 'We are currently in the infancy stage of genetic disorder testing.' While single sequencing testing is available, the hospital has not yet initiated whole-genome sequencing due to shortages in both human and laboratory resources.

Owing to various reasons, normally patients sent for genetic tests don't show up again, Dr. Urmila Shakya, senior pediatric consultant at the Shahid Gangalal Heart Center in Kathmandu, echoed Dr. Aryal's observation that even patients suspected of having genetic disorders hesitate to undergo testing due to the associated high costs.

'If the government had established an advanced lab in the country, I would not have had to suffer around New Delhi to diagnose my son's illness. I endured a lot mentally, physically, and financially,' Hari Bahadur shares, lamenting the government's lack of urgency in this regard.

Dr. Neelam Thakur, a consultant clinical geneticist at Bir Hospital, acknowledges that basic genetic testing, including carrier screening, mutation analysis, and cancer screening, is available locally. However, for advanced screening, patients are often referred abroad due to limited resources.

'We have forwarded the proposal to the line ministry to introduce next-generation sequencers and chromosomal microarrays for advanced testing at affordable costs,' Dr Thakur cautiously says that implementation may take years due to challenges such as a shortage of human resources, capital, and other resources.

Government intervention

The government is aware of the rare diseases in Nepal. 'We have followed the WHO's guidelines in recognizing the condition in Nepal,' says Dr. Prakash Budathoki, the spokesperson at the Ministry of Health and Population.

'We acknowledge that we have not been able to address the rare diseases issues in Nepal as much as we should have due to lack of funds and other resources,' Dr. Budathoki laments, highlighting the struggle to provide basic healthcare to citizens as outlined in the constitution of Nepal.

'At a time when we are struggling to provide basic care to people, addressing issues and providing better care, treatment, and services for rare genetic disorders remains a distant dream due to resource constraints,' Dr. Budathoki emphasizes.

At least the government has taken the initiative to set up a basic genetic lab in Bir Hospital, though it may not be sufficient to address the advanced forms of diseases.

Referring to the query about orphan drugs, which Hari Bahadur desperately sought for his infant son, Dr. Budathoki states that the government is aware of the plight of patients in securing these life-saving drugs.

The government is coordinating with Nepal Drugs Limited in this regard. 'We are cognizant of the legal, customs, and other regulations involved in importing orphan drugs, and cabinet decisions are required to facilitate this process,' he adds.

Way forward

While the diagnosis and prognosis of rare diseases in Nepal are in their infancy, there is a pressing need for an extensive public awareness campaign to educate the general population about these rare conditions, Dr Neeraj Parajuli says adding that awareness is needed to bring this into the forefront.

Health practitioners emphasize the formation of patient advocacy groups to bring together the government, health professions, and drug manufacturers to foster better diagnosis, treatment, and care.

Dr. Rajan Pandey advises that the government expedite the harmonization of newborn screening, improve data collection and evidence generation, integrate rare disease management into existing healthcare structures, amplify patient voices in decision-making, and establish a registry of rare diseases, among other initiatives.

'Without any delay, the government should initiate mental and social support to patients and families in conjunction with the Department of Health,' states Dr. Rupesh Mishra. He emphasizes that such counseling would help patients understand and accept their conditions, enabling them to live their lives accordingly.

In light of the costs associated with genetic testing, Prabha KC of MDF-N emphasizes the urgent need for the government to establish an advanced genetic testing laboratory to alleviate the plight of numerous patients and families facing similar stresses, akin to that of Hari Bahadur's in Nepal.

'In coordination with various stakeholders in Nepal, we can achieve the UN-envisioned Universal healthcare for all. As outlined by the UN resolution, no one is to be left behind,' says Nirmal Khadka, the Chairperson of Rare Disease Society Nepal.