VOLUME 16 NUMBER
6 November/December 2003
Cystic Fibrosis in India: [PDF]
Cystic fibrosis (CF) was first described as a clinically distinct
entity in 1938 by Anderson. Initially, it was considered a rare
and lethal disease of infancy. Over the past six decades, major
advances in the understanding of CF have resulted in an increase
in the median age of survival to 30 years.1
Cystic fibrosis is the most common life-limiting genetic disorder
in Caucasians with an incidence of approximately 1 in 2500 children
born in the UK.2 It is less common in African Americans (1 in
15 000) and Asian Americans (1 in 31 000). It also affects other
ethnic groups such as Blacks with an incidence of 1 in 17 000
and native Americans with an approximate incidence of 1 in 80
Cystic fibrosis was thought to be extremely rare in India and
was first reported in 1968.5,6 However, a recent review of all
cases of CF reported in the literature indicates that the disease
is probably far more common in people of Indian origin than previously
thought, but its diagnosis is missed in the majority of cases.7 The precise incidence of CF among Indians is unknown. The estimated
incidence of CF in the migrant population from the Indian subcontinent
in the USA is 1 in 40 000,8 and that in the UK is 1 in 10 000–12
000.9,10 A recent study on 955 cord blood samples reported a
carrier rate of the common mutation DF 508 (DF 508) as 0.4%.11 By using the same data the incidence of CF in India is estimated
to be 1 in 40 000.
The CF gene was identified in 1989. It is located on the long
arm of chromosome number 7 at position 7qI3,12,13 and more than
a thousand mutations in the gene have been recognized.14 The
basic defect in CF is a mutation in the gene for the chloride
conductance channel, i.e. cystic fibrosis transmembrane conductance
regulator. This results in an abnormality of cyclic adenosine
monophosphate regulated chloride conductance by epithelial cells
on the mucosal surface. The failure of chloride conductance leads
to dehydration of secretions that become viscid and are difficult
to clear.15 The prevalence of genetic mutations varies from one
population to another. The commonest mutation is DF 508, which
constitutes about 70% of the total cases.16 The frequency of
this mutation in Indian children is reported to be between 19%
and 44%.7,8,10,17–20 In a report of 120 Indian children
with CF,20 the DF 508 mutation was identified in 45 chromosomes
(19%) out of the 240 tested; 19 patients (16%) were homozygous
and 7 (6%) were heterozygous for the mutation. The frequency
of DF 508 mutation was higher in patients whose parental origins
were from Pakistan. Out of 23 patients whose origin was traced
to Pakistan, 13 (56%) were positive for the DF 508 mutation.
The figure for patients originating from other parts of India
was 13 (13%) out of 97 patients. In a report from Pakistan describing
mutations in 15 patients, the DF 508 mutation was found in 60%
of the patients.21 The spectrum of mutations other than DF 508
in Indian patients is highly variable and some rare and new mutations
have also been described.17
It has been reported from other Asian countries. that there are
fewer children with DF 508 mutations as compared with the Caucasian
population. Desgeorges et al.22 identified 20 families living
in Lebanon for several generations who had at least one child
with CF. They showed that 10 different DNA alterations—including
two novel mutations—accounted for 88% of the CF alleles.
The DF 508 mutation was found in 37.5% of the CF alleles.
The clinical features of CF are variable, and depend on the age
at diagnosis, supportive care and treatment. It has been suggested
that CF is more severe in Asians.10 There are not many studies
which document the clinical features in Indian children. A review
of 20 Asian children diagnosed with CF till 1994 in the USA suggests
that the mean age at diagnosis was delayed to 12 months as compared
to 6 months in their American counterparts. In a study of 18
children from Chandigarh, the mean age at diagnosis was 4.8 years
and the mean duration of symptoms was 4.1 years, suggesting a
In a recent report of 120 patients with CF20 from the All India
Institute of Medical Sciences, New Delhi it was observed that
most of the clinical manifestations at the time of presentation
were similar to those reported from the West and included recurrent
or persistent pneumonia, failure to thrive, malabsorption, rectal
prolapse, history of dehydration in the past, meconium ileus,
salt craving, salty taste on kissing and skin rashes. The clinical
manifestations that were different from the western series on
CF included: vitamin A and D deficiencies, lower CF clinical
scores suggesting advanced stage of illness at the time of diagnosis,
hypochloraemic alkalosis, higher colonization rate with Pseudomonas
and lower rates of common mutations.20
It has also been reported that the frequency of different morphotypes
of Pseudomonas aeruginosa as well as the antibiotic resistance
in these strains were higher in Indian children with CF, and
some of them were colonized by phenotypically and genotypically
distinct strains of Pseudomonas aeruginosa, which has an implication
for the management of these patients.24
The diagnosis of CF is based on clinical features and demonstration
of high sweat chloride values. To avoid false-positive and false-negative
results, the sweat test should be done by experienced laboratories
and must be repeated 2–3 times.25 After the identification
of CF mutations in 1989, it was believed that the diagnosis would
be easy. However, because of the large number of known mutations
(>1000) and their geographic variability, diagnosis by mutations
alone is not easy. In the USA, testing for 64 mutations provided
a sensitivity of 70%–95% in all ethnic groups except Asians
and at least 81% when the US population was considered as a whole.26
The wider mutation profile in Indian patients has not been investigated.
In a study on 24 patients in whom 18 exons of the CF gene were
screened using single strand conformational polymorphism (SSCP)
it was observed that DF 508 was present in 40% and the remaining
mutations were multiple in accordance with the multi-ethnic background
of the patient population.17
Facilities for the identification of CF mutations are not readily
available in India. The sweat test remains the best diagnostic
tool. However, attempts should be made to identify mutations
for further evaluation, patient counselling and prenatal testing.
In the absence of sweat chloride estimation and mutation analysis
at most centres in India, CF may be suspected on the basis of
supportive investigations. These include low or low normal serum
sodium and potassium, metabolic alkalosis and hypochloraemia,
isolation of Pseudomonas aeruginosa or Burkholdelia cepacia from
sputum or cough swabs, exocrine pancreatic deficiency below 20 years of age or azoospermia in postpubertal patients.
While CF does occur in Indian children, its precise magnitude
is not known; but the clinical features are typical. The diagnosis
is often delayed and at presentation the disease is therefore
advanced in most patients. They may have evidence of fat-soluble
vitamin deficiency and laboratory evidence of hypochloraemic
metabolic alkalosis with hypokalaemia. A major proportion of
these patients are colonized with Pseudomonas aeruginosa at the
time of diagnosis. The common mutation DF 508 is less frequently
seen in Indians than in Caucasians. Apart from creating an awareness
about CF among healthcare workers, it is also necessary to develop
diagnostic and treatment facilities for such patients.
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