1. Determinants & Magnitude of Cystic Fibrosis in The Gaza Strip
Amjad Fathi Hussein El-Shanti
MD, MPH, Doctorate of Public Health (Epidemiology)
Medical director of CFFC-Gaza
April-2014

2. Contents Introduction: CF in Gaza Strip Conclusion Recommendations
Definition of Cystic fibrosis (CF)
Epidemiology of CF ( Magnitude and Genotype Distribution)
Pathogenesis of CF
Clinical Manifestations of CF
Diagnosis of CF
Treatment
CF in Gaza Strip
Conclusion
Recommendations

4. What is cystic fibrosis (CF)?
Definition
What is cystic fibrosis (CF)?
What is cystic fibrosis (CF)?
A multisystem disease
Autosomal recessive inheritance
Cause: mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
chromosome 7
codes for a c-AMP regulated chloride channel
A multisystem disease
Autosomal recessive inheritance
Many functions still under investigation----CFTR
Rosenstein, BJ and Zeitlin, PL. Cystic fibrosis. The Lancet. 351:
Rosenstein, BJ and Zeitlin, PL. Cystic fibrosis. The Lancet. 351:

5. Autosomal recessive inheritance in CF
Let C= normal CFTR
Let c= mutant CFTR
If mom and dad are both carriers then:
With mom and dad carriers, then:
50% chance of having child who is a carrier
25% chance of child being affected
25% of child with no mutant copies of CFTR C c CC Cc C Cc cc c

6. Definition
Cystic Fibrosis (CF) or mucoviscidosis is an inherited disease of the exocrine glands, primarily affecting the GI and respiratory systems, and usually characterized by COPD, exocrine pancreatic insufficiency, and abnormally high sweat electrolytes, causing progressive disability and often, early death.
It is caused by a mutation in a gene called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

7. Epidemiology of Cystic Fibrosis

8. Magnitude and genotypic distribution
Birth prevalence is traditionally cited as 1 in 2,000 to 1 in 2,500 live births in Caucasian populations.
For Non-Caucasian countries, the problem of estimating birth prevalence of CF is even greater, and good estimates are lacking.

9. Magnitude and genotypic distribution
In UK, in 2003, the prevalence of CF was of 11.7 per 100,000.
In Canada, the prevalence was 10.5 per 100,000 (based on 2002 patient registry data and 2005 population estimates).

10. Magnitude and Genotypic Distribution
The incidence of CF among Arabs is estimated to range from rare to as common as the Caucasian populations.
Reports indicated frequencies ranging from 1:5800 in Bahrain, to 1:2650 in Jordan.
In Egypt, CF is more common than previously anticipated with an incidence rate of 1:2664.

11. Magnitude and Genotypic Distribution
The commonest mutation identified in the world is DF508, which comprises 66% of global mutations, followed by G451X and G551D which are responsible for 2.4% and 1.6% of the mutations respectively.

12. Magnitude and genotypic distribution:
Survival and mortality rate are useful indicators of clinical outcome, and are likely to be influenced by a variety of factors.
The CDR for CF in 2003 in the UK is only 0.17 per 100,000 general population.
In USA, standardized mortality has been shown to vary significantly with genotype, being as low as 4.4 per 1000 person-years at risk for certain genotype combination and as high as 25 per 1000 for others.

13. Risk factors & determinants
Non genetic factors:
Gender
Skin color and race
Birth weight
Consanguinity
Socioeconomic status
Environmental factors
Patient adherence to prescribed medical regimens
Genetic Factors:
CFTR gene mutations
Modifying genes

14. Pathogenesis of CF

15. Pathogenesis
The CFTR gene is found in region q31.2 on the long (q) arm of human chromosome 7.

16. CFTR Gene and Protein
Gibson, RL, Burns, JL, and Ramsey, BW. Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis. AJRCCM 168 ( ); 2003.

17. Pathogenesis
The CFTR protein transports chloride ions (Cl-) ions across the membranes of cells of the lungs, liver, pancreas, digestive tract, reproductive tract, and skin.
It is made up of five domains:

18. Types of mutations in CFTR
Class I
Defective protein production
Class II
Defects in processing
ΔF508
Class III
CFTR reaches cell surface but regulation is defective (channel not activated)
Class IV
CFTR in membrane with defective conduction
Class V
Decreased synthesis of CFTR
htmldocs/CFText/genetics.htm

19. Pathogenesis
Mutations in the CFTR gene have been classified into five different groups according to the mechanism by which they disrupt CFTR function.
Class
Effect on CFTR protein
Example of mutation I
Shortened protein
W1282X II
Protein fails to reach cell membrane
ΔF508
III
Channel cannot be regulated properly
G551D IV
Reduced chloride conductance
R117H V
Reduced due to incorrect splicing of gene
3120+1G>A

20. 5 Classes of CFTR Mutations
Defective
Production II
Defective
Processing
III
Defective
Regulation IV
Defective
Conductance V
Reduced
Amounts

21. CFTR and Airway Surface Liquid
Donaldson,SH and Boucher,RC. Update on the pathogenesis of cystic fibrosis lung disease.
Current Opinion in Pulmonary Medicine. 9: ; 2003.

22. Airway surface liquid low volume hypothesis
Mucus---helps clear airway of bacteria
Clearance of mucus depends on
Ciliary function
Mucin secretion
Volume of airway surface liquid (ASL)
Forms periciliary liquid layer
Dilutes mucus---facilates entrapment of bacteria and clearance
Optimal volume of ASL regulated by Na+ absorption and Cl- secretion
Donaldson,SH and Boucher,RC. Update on the pathogenesis of cystic fibrosis lung disease.
Current Opinion in Pulmonary Medicine. 9: ; 2003.

23. Airway surface liquid low volume hypothesis
Normal CFTR inhibits a sodium channel (ENaC)
Mutant CFTR----ENaC not inhibited
Sodium absorption is increased
Water follows sodium
ASL volume decreases
Normal CFTR will cause Cl- ions to be secreted if the ASL fluid is low
Mutant CFTR Cl- ions not secreted
Donaldson,SH and Boucher,RC. Update on the pathogenesis of cystic fibrosis lung disease.
Current Opinion in Pulmonary Medicine. 9: ; 2003.

24. Airway surface liquid low volume hypothesis
Cilia do not beat well when PCL volume is depleted
Mucins are not diluted and cannot be easily swept up the airway
Mucus becomes concentrated
Results in increased adhesion to airway surface
Promotes chronic infection
Donaldson,SH and Boucher,RC. Update on the pathogenesis of cystic fibrosis lung disease.Current Opinion in Pulmonary Medicine. 9: ; 2003.

25. From Mutation To Disease
The mutant form of CFTR
prevents chloride transport,
causing mucus build-up
Mucus clogs the airways
and disrupts the function of
the pancreas & intestines.

26. Pathophysiology of CF ? CFTR Dysfunction Disease manifestations Lungs
Sinuses
Pancreas
Liver
Bones
Vas deferens ?

27. Clinical Manifestations of CF

28. Clinical Manifestations of CF
Chronic Sino-Pulmonary Disease
Nutritional deficiency/GI abnormality
Obstructive Azoospermia
Electrolyte abnormality
CF in a first degree relative
Cystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic fibrosis.1997.

29. Clinical Manifestations of CF

30. Chronic Sino-Pulmonary Disease
Chronic infection with CF pathogens
Endobronchial disease
Cough/sputum production
Air obstruction---wheezing; evidence of obstruction on PFTs
Chest x-ray anomalies
Digital Clubbing
Sinus disease
Nasal Polyps
CT or x-ray findings of sinus disease
Cystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic fibrosis.1997.

31. Infection
Age-specific prevalence of airway infections in patients with CF. Organisms reported to the U.S. Cystic Fibrosis Patient Registry, 2001 Early infections in CF airways are most frequently caused by S. aureus and H. influenzae. natural history study of patients with CF in the first 3 years of life, the mean age of detection of an antibody response to P. aeruginosa was approximately 15 months, whereas the mean ages of first positive upper and lower airway culture were approximately 21 and 23 months
Gibson, RL, Burns, JL, and Ramsey, BW. Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis. AJRCCM 168 ( ); 2003.

32. Prevalence of Infections in CF Patients
100
P. aeruginosa
S. aureus
MRSA
H. influenza
S. maltophilia
B. cepacia 80 60
Percent 40 20
0 to 1
2 to 5
6 to 10
11 to 17
18 to 24
25 to 34
35 to 44
45+
Age (years)
Cystic Fibrosis Foundation Patient Registry Data. 2005

33. CF Infections---Pseudomonas aeruginosa
80% CF patients eventually infected with pseudomonas
Association between acquiring pseudomonas and clinical status deterioration
Form biofilms
Relatively large genome
Pseudomonae collected from sputa of CF patients have been noted to have larger genomes than lab strains
Biofilms are sessile communities of bacteria that form in aggregates on surfaces using a hydrated polymeric matrix of their own synthesis (Figures 6D and 6E). Some common clinical characteristics of biofilm infections have been identified: slow growth of organisms, stimulation of production of antibodies that are ineffective in clearing bacteria, inherent resistance to antibiotics, and an inability to eradicate biofilm infections even in hosts with intact immune systems (134–137).
Gibson, RL, Burns, JL, and Ramsey, BW. AJRCCM 168 ( ); 2003.

34. Pseudomonas genome

35. Burkholderia cepacia complex
B. cepacia syndrome: fevers, rapidly progressive necrotizing pneumonia, death
Chronic cepacia infection decreased lung function and increased mortality
Several closely related species termed genomovars1
Holmes, A, Govan, J, and Goldstein, R. Agricultural Use of Burkholderia
(Pseudomonas) cepacia:
A Threat to Human Health?
Emerging Infectious Diseases. 4(2): ; 1998
Nine recognized genomovars
Most common are II, III, V
1. Gibson, RL, Burns, JL, and Ramsey, BW.
AJRCCM 168 ( ); 2003.

36. Endobronchial disease
Hyperinflation
Peribronchial cuffing
Bronchiectasis
Diffuse fibrosis
Atelectasis
From:

37. Nasal Polyps Benign lesions in nasal airway
If large enough, can be associated with significant nasal obstruction, drainage, headaches, snoring
Likely associated with chronic inflammation
May need surgical intervention
High recurrence rate
From:
ped/topic1550.htm

38. Digital Clubbing Bulbous swelling at end of fingers
Normal angle between nail and nail bed lost (Schamroth sign)
Can be associated with pulmonary disease, cardiac disease, ulcerative colitis, and malignancies
From: Fawcett et al., 2004

39. Nutritional deficiency
Pancreatic insufficiency
Pancreatic enzymes stay in ducts and are activated intraductally
Autolysis of pancreas
Inflammation, calcification, plugging of ducts, fibrosis
Malabsorption
Failure to thrive
Fat soluble vitamin deficiency
Davis, P. Cystic Fibrosis Since AJRCCM Articles in Press.
Doi: /rccm OE; 2005.
2. Quinton, P. Physiologic Basis of Cystic Fibrosis. Physiol Rev 79:3-22, 1999.

40. GI disease Intestinal abnormality Hepatobiliary disease
Meconium ileus
Distal intestinal obstruction syndrome (DIOS)
Rectal prolapse
Hepatobiliary disease
Focal biliary cirrhosis
Multilobular cirrhosis
Pancreatic endocrine dysfunction
Cystic fibrosis related diabetes

41. Cystic fibrosis related liver disease
Focal inspissation of bile
Obstructs biliary ductules
Second leading cause of death in CF1
Prevalence 9-37%1
Spectrum of disease
increased liver enzymes
biliary cirrhosis
portal hypertension
Ursodiol increases bile flow {02} . In chronic cholestatic liver disease, ursodiol appears to reduce the detergent properties of the bile salts, thus reducing their cytotoxicity. Also, ursodiol may protect liver cells from the damaging activity of toxic bile acids (e.g., lithocholate, deoxycholate, and chenodeoxycholate), which increase in concentration in patients with chronic liver disease
1. Efrati, O et al., Liver Cirrhosis and portal hypertension in CF.
European Journal of Gastroenterology and Hepatology. 15(10): ; 2003.

42. Cystic fibrosis related diabetes mellitus
Screening
Oral glucose tolerance test (OGTT)
Every two years in patients years
Any patient with random plasma glucose >180
Fasting>=140 mg/dl
initiate insulin treatment
Fasting<140 and OGTT at 2 hrs>200 mg/dl
Home glucose monitoring; consider insulin
Fasting <140 and 2 hour
Impaired glucose tolerance
OGTT annually
Fasting and 2 hour <140
Normal glucose tolerance

43. Infertility
Men
Abnormal embryologic development of the epididymal duct and vas deferens---may be incomplete of absent1
Congential bilateral absence of the vas deferens—97-98% of men with CF 1
1. Lewis-Jones et al, Cystic fibrosis in infertility: screening before assisted reproduction: Opinion. Human Reproduction 15(11):

44. Infertility Women Pregnancy and CF:
Lower fertility rate than non-CF women
Viscid mucoid cervical secretions of low volume in women with CF 1
Pregnancy and CF:
Goss et al, no significant difference in survival in women who became pregnant with CF compared to women who did not become pregnant (after adjusting for disease severity)2
1.Quinton, P. Physiologic Basis of Cystic Fibrosis. Physiol Rev 79:3-22, 1999
2.Goss, CH, Rubenfeld, GD, Otto, K and Aitken, ML. The effect of pregnancy on survival in women with cystic fibrosis. Chest 124(4): ; 2003.

45. Electrolyte abnormality---history
Dr. Paul di Sant’ Agnese
1949 NYC heat wave----noted CF infants to have a higher rate of heat prostration than non-CF
Showed that sodium and chloride concentration in CF patients’ sweat was 5 times higher than in non-CF1
Became basis for sweat chloride test
Davis, P. Cystic Fibrosis Since American Journal of Respiratory and Critical Care Medicine Vol 173. pp , (2006)

46. Electrolyte abnormality
Clinically---hypochloremic metabolic alkalosis
CFTR on luminal side of sweat duct
Chloride goes in from lumen via CFTR and out to blood by other transporters
Sodium goes in via ENaC
Defective CFTR---Na and Cl- movement and reabsoprtion into lumen impeded
Goodman, B and Percy, WH..CFTR in Teaching Membrane Transport. Adv Physiol Educ. 29 (79-82); 2005

47. Genetic Determinants of severity of disease
The variability in disease severity in patients with CF is not a consequence of relative preservation of pancreatic function but is a result of different gene mutants, together with additional factors, genetic and /or environmental.
The location of a mutation along the CFTR gene has no direct effect on severity of CF disease.

48. Diagnosis of Cystic Fibrosis
One or more clinical manifestations of CF
PLUS
Two CF mutations OR
Two positive quantative pilocarpine iontophoresis sweat chloride values
An abnormal nasal transepithelial potential difference value

49. Diagnostic criteria for cystic fibrosis Part 1: Clinical Manifestation of Disease
At least one of the following:
1) One or more clinical manifestations of CF
Meconium ileus
Chronic bronchitis / bronchiectasis
Chronic infection of the paranasal sinuses
Pancreatic insufficiency
Salt loss syndromes
Male infertility due to congenital bilateral absence of the vas deferens
2) Positive newborn screening test
3) History of CF in a sibling

50. At least one of the following:
Diagnostic Criteria for Cystic Fibrosis Part 2: Laboratory evidence of CFTR abnormality
At least one of the following:
1) Elevated sweat chloride test
2) Identification of a mutation in each CFTR gene known to cause CF
3) In vivo demonstration of characteristic abnormalities in ion transport across nasal epithelium (not widely available)

51. Sweat Test

52. Sweat Test for Diagnosis of CF20 40 60 80
100
120
140
160
180
mEq/L
300
600
900
1200
1500
1800
240
Number of normal controls
Number of patients with CF
Controls
n=4269 CF
n=920
Shwachman H, Mahmoodian A. Mod Prob Pediatr 1967;10:158

53. A perspective on the Sweat Test
The “sweat test” provides laboratory confirmation of the clinical diagnosis of Cystic Fibrosis.
This occurs because of an abnormally high salt concentration in their eccrine sweat, ranging from 3-5 times higher than that of normal children.

54. A perspective on the Sweat Test
The sweat Test was first described in 1959 by Gibson & Cooke and remains the “ Gold Standard” for the diagnosis of cystic fibrosis.
In the majority of CF patients with typical features and identified CFTR mutations, the sweat test is diagnostic.
In atypical forms, the sweat chloride levels may fall into the intermediate range and there are rare examples of patients with CF, confirmed on genetic testing, who have a normal sweat test.

55. SWEAT TESTING PROCEDURE WESCOR MACRODUCT
Sweat Analysis
Sweat Stimulus & Collection

56. Sweat chloride Positive Sweat chloride: 60-165 meq/L
Borderline sweat chloride: meq/L
Normal sweat chloride: 0-40

57. Sweat chloride False positives: Anorexia Nervosa Autonomic dysfunction
Addison disease
Ectodermal dysplasia
Eczema
Edema
Fucosidosis
Glucose-6-Phosphate dehydrogenase deficiency
Glycogen storage disease Type 1
Hypothyroidism
Hypoparathyroidism
Malnutrition from various causes including HIV infection
Nephrogenic diabetes insipidus
Nepohrosis
Lab error (evaporation or contamination of sample)
Davis, P. Cystic Fibrosis Since AJRCCM Articles in Press.
Doi: /rccm OE; 2005.

58. Sweat Chloride False negatives: Edema Malnutrition Some CF mutations
Sample diluted
Davis, P. Cystic Fibrosis Since AJRCCM Articles in Press.
Doi: /rccm OE; 2005.

59. Use of Genotyping to Diagnose CF
Population Frequency of Specific CFTR Mutations Causing CF
ΔF508
1601 CFTR mutations known to cause CF
Only 25 mutations have a frequency > 0.1%
G542X
R347P
kbC  T
Δ I507
R117H
R1162X
1717-1G  A
R553X
621+1G  T
W1282X
N1303K
G551D 10 20 30 40 50 60 70
Frequency, %
CF Genetic Analysis Consortium

60. Genotyping for CF Diagnosis
Current commercial screening tests
Look for presence of between mutations
These will detect a CF allele only ~90% of time
For a group of patients with known CF, genotyping would be diagnostic in only ~81% of patients
 Screening for most common mutations is not as sensitive as sweat testing (98%) to diagnose classic CF

61. Genetic Diagnosis of CF
Tests becoming commercially available for detecting mutations more broadly
PCR used to amplify all exons and surrounding splice sites
Heteroduplex formation screening and/or sequencing
Analysis for large deletions and duplications

62. Treatment

63. It gets more complicated......

64. Treatment
The only way to cure CF would be to use gene therapy to replace the defective gene or to give the patient the normal form of the protein before symptoms cause permanent damage.

65. The major goal in treating CF is:
to clear the abnormal and excess secretions and
to control infections in the lungs, and
to prevent obstruction in the intestines.
For patients with advanced stages of the disease, a lung transplant operation may be necessary.
Although treating the symptoms does not cure the disease, it can greatly improve the quality of life for most patients and has, over the years, increased the average life span of CF patients to 30 years.

66. Treatment of Acute Exacerbations of CF Lung Disease
Antibiotic treatment
Oral antibiotics
If symptoms are mild, and
Bacteria are susceptible
Intravenous antibiotics otherwise

67. Management of Chronic Lung Disease in Cystic Fibrosis

68. Aerosolized Antibiotics
High dose tobramycin proven for chronic infection
TOBI® 300 mg in 5 ml bid every other month
Ramsey B, et al. NEJM 1999;340:23-30

69. Mucolytic Therapy for CF
DNase (Pulmozyme ®)
Chronic use improves FEV1 and causes fewer exacerbations
Fuchs HJ, et al. NEJM 1994;331:

70. Bronchodilators in CF
No studies in acute exacerbations but routinely given
Chronic use -- FEV1 improves acutely in some patients
b-adrenergic agonists (e.g. albuterol, salmeterol)
Anticholinergic agents (ipratroprium bromide, tiotroprium)

71. Anti-Inflammatory Treatment in CF
Glucocorticoids
Oral (prednisone)
Preserves lung function, but too many adverse effects
Inhaled
Used for subgroup of with bronchial hyperreactivity (asthma) symptoms
Ibuprofen
Beneficial for young patients
No evidence for improvement in adults

72. Macrolide Therapy for CF4 12 24 28 -4 -2 2 5
Study Week
Azithromycin
Placebo 1 -1 -3 3
Change in FEV1 (% predicted) 8 16 20
Azithromycin in CF
Improved FEV1
Fewer exacerbations of CF lung disease
Uncertain mechanism of action
Anti-inflammatory?
Bacterial toxin or biofilm production?
Saiman L, et al. JAMA. 2003;290:

73. Nebulized Hypertonic Saline (7%)
Effect on FEV1
Randomized, double-blind, placebo controlled trial
N = 164
Inhalation of 4 ml of 7% vs. 0.9% saline bid for 48 weeks
Elkins MR et al. N Engl J Med 2006;354:

74. Effect of 7% Saline on Frequency of Pulmonary Exacerbations
Elkins MR et al. N Engl J Med 2006;354:

75. Physiotherapy for CF No studies in acute exacerbations
But “standard of care” treatment
Beneficial for chronic management

76. Gastrointestinal Treatment
Modified diet
Due to pancreatic disorders, children with CF require a modified diet, including vitamin supplements (vitamins A, D, E, and K) and pancreatic enzymes.
Maintaining adequate nutrition is essential. The diet calls for a high-caloric content (twice what is considered normal for the child's age), which is typically low in fat and high in protein.
Patients or their caregivers should consult with their health care providers to determine the most appropriate diet.

77. Gene Therapy
Gene therapy is the use of normal DNA to "correct" for the damaged genes that cause disease.
In the case of CF, gene therapy involves inhaling a spray that delivers normal DNA to the lungs.
The goal is to replace the defective CF gene in the lungs to cure CF or slow the progression of the disease.

78. CF in Gaza Strip

79. Magnitude of CF disease in GS
The average annual incidence rate of CF disease through the last ten years ( ) in the Gaza strip was 1.26 case per 5000 live births.
Incidence rates of cystic fibrosis disease (Gaza, )

80. Prevalence rates of cystic fibrosis disease (Gaza, 2000- 2010)
Magnitude of CF disease in GS
The average annual prevalence of CF disease through the last ten years in Gaza strip was 3.72 cases per 100,000 population.
Prevalence rates of cystic fibrosis disease (Gaza, )

81. Magnitude of CF disease in GS
Mortality
The average annual mortality rate due to CF in the Gaza Strip through the last ten years ( ) was 0.26 case per 100,000 populations.
The average annual CFR of CF through the last ten years was 9.18%.

82. Magnitude of CF disease in GS
CF diagnosis
The mean age of CF cases at diagnosis was months. (98% of cases were infants at time of diagnosis).

83. Magnitude of CF disease in GS
Clinical manifestations and hospitalizations of CF patients
All cases were recurrently admitted to hospital, The average admission times was times/year among cases.
Distribution of cystic fibrosis cases by the affected systems (Gaza,2010)

84. Magnitude of CF disease in GS
Nutritional indicators of CF cases and controls
Average anthropometric measurements and nutritional indicators of cystic fibrosis cases and controls (Gaza, 2010)
Variable
Cases (n= 100)
Controls (n= 100)
T-Test
Average
S.D T P
Height (cm)
99.64
20.10
112.10
16.6 2
-4.78
0.000*
HAZ
-2.42
1.80
0.07
2.09
-9.01
Weight (kg)
14.70
5.84
19.89
7.44
-5.48
WAZ
-2.48
1.05
-0.26
1.67
-11.28
WHZ
-1.67
1.82
-0.02
2.06
-5.98
*Statistically significant

85. Average hemoglobin level of CF cases and controls (Gaza, 2010)
Magnitude of CF disease in GS
Nutritional indicators of CF cases and controls
This difference was a statistically significant (t=-13.71, p =0.00).
Average hemoglobin level of CF cases and controls (Gaza, 2010)

86. Risk factors associated with CF disease in GS
Sociodemographic factors
Distribution of cases and controls by sociodemographic factors (Gaza, 2010)
Male Gender (OR=2.35, 95% CI=1.26, 4.04, p=0.004).
Fair Skin Color (OR=5.43, 95% CI=2.11, 14.50, p=0.000).
Consanguinity (OR=13.20, 95% CI=5.94, 29.95, p=0.000).
North Gaza Governorate (OR=2.006,95%CI=1.04,3.853, p=0.035).

87. Genetic determinants of CF disease in GS
The results of mutation testing revealed that 61% of known mutation-CF cases have at least single allele of F508.
Also 12.2% of known mutation-CF cases were of homo kb CFTR mutation.
Also 14.7% of known mutation-CF cases were of homo N1303k CFTR mutation, homo G85E CFTR mutation, and homo 3120del 18.6kb CFTR mutation equally.  

88. Genetic determinants of CF disease in GS
CF disease Classes
CF Cases No %
Class I 2
4.9
Class II 21
51.2
Class III
Class IV 1
2.4
Class V 8
19.5
Compound 9 22
Total 41
100

90. The majority of the cases was diagnosed during infantile age and was diagnosed in Governmental Pediatric Hospitals by both manifestations and sweat test.

91. The anthropometric measurements and hemoglobin level of CF cases in the GS reflected that short stature, underweight, wasting and anemia were very common.
About two thirds of known mutation of CF cases have at least a single allele of DF508, which is considered of severe type of CFTR mutations.

92. RECOMMENDATIONS

93. Recommendations concerning CF services
Neonatal screening programs for CF disease should be set up.
The importance of establishing a reliable diagnosis of CF using a properly conducted sweat test. In addition, diagnostic radiology, and laboratory facilities.
Integration of genetic counseling and services for CF cases’ families into primary health care.

94. Setting an expanded comprehensive health educational program for families of CF cases’, old CF cases, and general public about CF and strengthening the nutrition program for the public.
Supplies of pancreatic enzymes and basic antibiotics, including anti-Pseudomonas agents for CF patients free of charge .
It is essential for health authorities to know the magnitude of the problem if they are to make appropriate provisions for CF care.
It is important to establish and maintain a national CF registry in order to identify and predict the need for services and to monitor survival trends.

95. Recommendations for improving socioeconomic & environmental status
Increasing the situation of women in the community by encouraging the high education of girls, and involving the women in all fields and works.
Increasing community awareness and counseling concerning the effect of early marriage and consanguineous marriage.

96. Campaigns aiming at educating families on the importance of clean drinking water as well as advising mothers to take compensatory measures such as additional nutrition intakes.
Local authorities should inform the public about local concentrations of air pollutants, possible effects on health, and the action taken to minimize any health risks.