Night Blindness and Diabetes in a Non-Caucasian

World Applied Sciences Journal 23 (6): 837-839, 2013 ISSN 1818-4952 © IDOSI Publications, 2013 DOI: 10.5829/idosi.wasj.2013.23.06.187

Night Blindness and Diabetes in a Non-Caucasian Cystic Fibrosis Patient in Iran Reza Tabaripour, 2Mohammad Reza Esmaeili Dooki and 3Haleh Akhavan-Niaki 1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 2 Non-Communicable Pediatric Diseases Research Center, Babol University of Medical Sciences, Babol, Iran 3 Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran 1

Submitted: Jan 2, 2013;

Accepted: Feb 9, 2013;

Published: Jul 27, 2013

Abstract: Cystic fibrosis (CF) is an autosomal recessive lethal disease that is predominantly occur in the caucasian populations and causes many clinical signs. The major clinical signs are pancreatic insufficiency and progressive lung disease but night blindness and diabetes are less well known. We report a fifteen years old non-caucasian girl that have cystic fibrosis with atypical night blindness, diabetes and nasal polyps symptoms in addition to some of major clinical symptoms. Molecular analysis of this patients showed that she was homozygote for 1677delA mutation. Clinical signs in CF are vast and related to organs which are affected. patients may present typical or atypical conditions. with progress in the management of cystic fibrosis and improvement in life expentancy, several atypical symptoms are expected to emerge. So it is important to screen patients for possible co-morbidities. Key words: Cystic fibrosis

Night Blindness

Reverse Dot Blot

INTRODUCTION

Diabetes

perform well, with aging of this girl the troubles became worse until she got confronted with polyuria and polydipsia. The FBS tests (average: 250 mg/dl) indicated that she was suffering from CF related Diabetes (CFRD), thus she was treated with insulin. Serum levels of vitamin A (NR= 0.3 to 4.5 µmol/L) were the lowest normal value, rated 0.31 and she showed with night blindness during last year. Serologic tests illustrated that, the amount of Aspartate aminotransferase; alkaline phosphatase and alkaline aminotransferase were 20 IU/L (NR=1 to 40 IU/L), 559 IU/L (NR=116 to 480 IU/L) and 27 IU/L (NR=1 to 50 IU/L) respectively. Her weight and height were 33kg and 152cm respectively and also her Body MassIndex (BMI) was therefore 14.3. Sweat tests were positive on three separate occasions with measured sweat chloride of 132 mmol/l (NR = 0 to 50 mmol/l). To determine the molecular pattern of CF in this patient, W128X, N1303K, G542X, R347P, G85E, 1525-1(G-A), 1677delA, 2183(AA-G), K1177X, S466X, L467F, 3130delA, 2789+5(G-A), F508del, R1162X and R334W mutations were screened based on thier frequencies in the world and neighbor countries around Iran using simple, rapid and non-radioactive Reverse Dot Blot (RDB) method [2]. Briefly the exons

Cystic fibrosis (CF) is an autosomal recessive lethal disease which occurs mainly in European derived population caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene [1] which encodes a protein expressed in the apical membrane of exocrine epithelial cells. The major clinical characteristics of CF are pancreatic insufficiency and progressive lung disease [1], but the eye manifestations of CF is among minor clinical symptoms that are less well known. We describe primary presentation of CF-related diabetes and night blindness in a fifteen years old girl for the first time in a non- caucasian population. Case Presentation: A fifteen years old non- Caucasian girl presenting with poor feeding conditions who suffer from Cystic fibrosis (CF) and showed signs of night blindness, diabetes and nasal polyps was referred to the hospital. This individual was representing respiratory problems, failure to thrive and malnutrition, abnormal stool, Anemia and Edema since the age of sixth month. As the family attention and referring to hospital didn’t Corresponding Author:

Mutation

Reza Tabaripour, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. Tel: +0111- 2193994, Cel: +09111151382.

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World Appl. Sci. J., 23 (6): 837-839, 2013

mechanisms such as pancreatic defect, the deficiency to absorb lipid soluble vitamins (A, K, E and D) and the reduction in concentration of retinol binding protein which cause navigation of retinol to liver. The vitamin A is also useful to maintain the mucus secretion in epithelial cells. The reduction of vitamin A level leads to worse clinical conditions [4] such as lung defect [5, 6] and reduced standard deviation of weight and bone density [4]. The night blindness is the most prevalent sign of vitamin A deficiency. The lack of CFTR activity in pancreatic channel leads to defection of pancreas secretion. The resulting inspissation of pancreatic secretions produces acinar destruction and then induces fibrosis and progressive adipose replacement of pancreatic tissue. This destructive process finally endangers the endocrine tissues which in conclusion may indicate diabetes symptoms. CF related diabetes is an age-related disease and its incidence prevalence rate increases about 5% per year [7]. In age of 30, 50% of patients comprise CFRD. the prevalence of CFRD through patient under 10 years is only 2% [8]. The frequency of CFRD among people more than 10 and 20 is 5 and 9.3% respectively [9] which in this observed patient diabetes symptoms were encountered at age 15.

Fig. 1: Results of Reverse Dot Blot (RDB) reaction. lane 1 indicate individual that was homozygote for 1677delA, lane 2 indicate normal individual, lane 3 indicate individual that was heterozygote for 1677delA mutation and lane 4 is negative control (without PCR product). (N: Normal, M: Mutant) where these mutations occured were amplified with biotinylated primers by using Polymerase Chain Reaction (PCR) and the PCR products were utilized in RDB assay. The result of RDB is shown in Figure 1 and indicate that she was homozygote for 1677delA mutation.

CONCLUSION The spectrum of clinical featuresof CF is wide and variable and this case showed an atypical presentation of diabetes and night blindness. The prevalence of CFRD increases with age, so screening by annual OGTT from the age of 10 is necessary and insulin therapy may improve CF status. It is also important to screen the patients in adolescence for night blindness and vitamin A deficiency and the patient had been commenced on replacement therapy of vitamin A. genetic analysis can be helpful for treatment of patients and carrier detection or prenatal diagnosis in families with previous history of the disease.

DISCUSSION There are variety mutations in CFTR gene that can be grouped into five classes according to their effect on the CFTR protein. Class I, II and III mutations generally lead to complete loss of function and a more severe disease and Class IV and V cause a reduction in function and have a milder effect, so Clinical symptoms in CF are vast and variable for many affected. Patients may represent typical CF clinical symptoms such as respiratory problems and malnutrition or may represent atypical conditions like pancreatic problems, congenital absence of the vas deferens and azoospermia, nasal polyps and diabetes in the late childhood or during puberty. This is the first reported case in non-Caucasian population, who is confronted with night blindness, diabetes and nasal polyps. a cystic fibrosis patient with similar clinical symptoms such as night blindness and clubbing of the hands was reported in caucasian populations and Genetic analysis identified the F508del and G542X mutations [3]. The lack of vitamin A may occur as a result of several

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