Rare disease: Causes, signs and symptoms, treatment, who should get tested

Rare disease is a disease that affects a small percentage of the population but most rare diseases are genetic in origin and are present throughout a person’s life even if symptoms do not immediately appear but it usually appears early in life and about 30% of children with rare diseases may die before reaching their 5th birthdays. The term “rare diseases or rare disorders" was referred to those diseases or disorders with a prevalence of 1 or less, per 1000 population by World Health Organization (WHO) and there is no universally accepted definition of rare diseases but in India, we generally accept that a disease prevalence of less than 100 patients per 100,000 people is categorized as a rare disease and there are about 6000-8000 known rare diseases reported in the medical literature.

As per National Consortium for Research and Development on Therapeutic for Rare Diseases, approximately 450 rare diseases have been identified and reported in India however, 80% of all rare disease patients are affected by approximately 350 rare diseases. The most common rare diseases that have clinically actionable treatment regimen include Haemophilia, Thalassemia, Sickle-cell Anaemia and Primary Immuno Deficiency in children, auto-immune diseases, Lysosomal storage disorders such as Pompe disease, Hirschsprung disease, Gaucher’s disease, Cystic Fibrosis, Hemangiomas and certain forms of muscular dystrophies.

In an interview with HT Lifestyle, Dr Vikram J Rao, Consultant and Head-Dept of General and Gastro-Intestinal Surgical Sciences at King Edward Memorial College and Seth G S Hospital, shared, “Familial adenomatous polyposis (FAP) is a rare disease with an incidence of approximately 1 in 10,000 life births. It affects all races and both genders equally. It is an inherited condition caused by a defect in the Adenomatous Polyposis Coli (APC) gene mutation which results in a generalised growth disorder expressed as benign and malignant tumors in a variety of tissues.”

He added, “It is a dominantly inherited syndrome with close to 100% penetrance. Children of an affected parent usually undergo genetic testing at puberty and if affected, should have an colonoscopy immediately. The possibility of Hepatoblastoma, a rare manifestation of the germline APC mutation is a reason to perform genetic testing of newborns and the Hepatoblastoma screening with a six monthly liver ultrasound and a blood investigations in the form of Alpha-fetoprotein until the age of 7 years.”

Dr Prashanth Bagali, Practice Head-Oncology at Strand Life Sciences, explained how is it tested or recognised and said, “There are two ways to do this - One- When it is prenatal, for the woman who is pregnant, the gynaecologist will take care of her health in terms of ultrasound or any other scan that is done after the 5th or 6th week. During this scan, she will be able to see if there are any deformities or any kind of deviation from the normal growth of the child. The gynaecologist can also refer the patient to a specialist. In the second method, the child is taken to the paediatrician or general physician and they are trained to look for any clinical symptoms for specific rare diseases.”

He elaborated, “They will either identify the disease or they will send the child’s sample for further testing. Sometimes, they will know with behavioural changes but if the symptoms aren’t there, we call it asymptomatic. In asymptomatic cases too, the doctor can take the call to send the child and parent for further testing. Genetic testing is now available in India. Therefore, rare diseases can be diagnosed by using different test methods such as microarrays or the next generation sequencing technology.”

Talking about who can get it and how to go about it if your child is diagnosed with a rare disease, Dr Vikram J Rao highlighted, “Care of patients with FAP and their families is best given by the centers of experience and excellence. Colorectal cancer (CRC) is a main risk in patients with FAP and is the main cause of death. The average age at the Cancer diagnosis is about 39 years with much younger onset in the patients with profuse polyposis. Symptomatic patients with presentation of pain in the abdomen or bleeding per rectum should undergo prophylactic Colectomy surgery using a oncologic technique as hidden cancer is elevated in the patient.”

He pointed out, “For patients who do not require Colectomy around the time of diagnosis should atleast have an annual Colonoscopy performed with removal of larger polyps and continued thoughtfulness of the timing of the surgery. Another important aspect is the fact that Duodenal cancer being the third most common cause of death in these patients upper GI surveillance with upper GI Endoscopy should begin at the age of 20-25 years.”

Bringing his expertise to the same, Dr Prashanth Bagali said, “Rare diseases are a serious public health concern in India, with an estimated burden of about 80 to 96 million cases reported annually. Moreover, 70-80% of rare diseases are of genetic nature, and thus are asymptomatic, but will appear in the person’s lifetime. Most of the affected communities are having high rates of consanguineous marriages (high genetic relatedness between individuals), high poverty, low education levels and inaccessible medical knowledge to make timely diagnosis of rare disease affected individuals. About 85-95% of rare diseases have no approved treatment and less than 1 in 10 patients receive disease specific treatment. About 50% of new cases are in children and are responsible for 35% of deaths before the age of 1 year, which has a catastrophic impact on families in terms of emotional as well as financial drain, as the cost of treatment is prohibitively high.”

He suggested, “Once a child is diagnosed with a rare disease, they are referred to a medical geneticist or to a neurosurgeon. The neurosurgeon or geneticist, will corroborate the symptoms with the genetic report. They will advise on the next steps and what the treatment should be. With the National Policy for Rare Diseases, all the doctors are aware about the insurance coverage and financial benefits to the parents of the child. Usually, depending on the financial situation of the parents and depending on the seriousness of the rare disease, the Government of India has started 8 centres of excellence to handle/manage rare diseases. All these centres have an information centre. The government has mandated that all the government hospitals in the district headquarters, in cities and even the private hospitals, should have an Information Centre for Rare Diseases so that patients can be directed to these 8 centres of excellence.”