Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome.

AIMS/HYPOTHESIS: Diabetes is one of the cardinal features of thiamine-responsive megaloblastic anaemia (TRMA) syndrome. Current knowledge of this rare monogenic diabetes subtype is limited. We investigated the genotype, phenotype and response to thiamine (vitamin B1) in a cohort of individuals with TRMA-related diabetes. METHODS: We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire. RESULTS: We identified 24 different mutations, of which nine are novel. The onset of the first TRMA symptom ranged from birth to 4 years (median 6 months [interquartile range, IQR 3-24]) and median age at diabetes onset was 10 months (IQR 5-27). At presentation, three individuals had isolated diabetes and 12 had asymptomatic hyperglycaemia. Follow-up data was available for 15 individuals treated with thiamine for a median 4.7 years (IQR 3-10). Four patients were able to stop insulin and seven achieved better glycaemic control on lower insulin doses. These 11 patients were significantly younger at diabetes diagnosis (p = 0.042), at genetic testing (p = 0.01) and when starting thiamine (p = 0.007) compared with the rest of the cohort. All patients treated with thiamine became transfusion-independent and adolescents achieved normal puberty. There were no additional benefits of thiamine doses >150 mg/day and no reported side effects up to 300 mg/day. CONCLUSIONS/INTERPRETATION: In TRMA syndrome, diabetes can be asymptomatic and present before the appearance of other features. Prompt recognition is essential as early treatment with thiamine can result in improved glycaemic control, with some individuals becoming insulin-independent. DATA AVAILABILITY: SLC19A2 mutation details have been deposited in the Decipher database ( https://decipher.sanger.ac.uk/ ).

Hypercalcemia as a rare presentation of hyaline fibromatosis syndrome from different Sudanese families: two case reports.

BACKGROUND: Hyaline fibromatosis syndrome is a rare progressive autosomal recessive connective tissue disorder caused by a mutation in the ANTXR2/CMG2 gene. According to its severity, patients may present with skin nodules or visceral infiltration, which carries a poor prognosis. Hypercalcemia has not been reported as a presenting feature of this syndrome. Stimulation of osteoclasts by inflammatory factors and immobilization--induced hypercalcemia have played role in the pathophysiology. To our knowledge, this is the first report of hypercalcemia-associated hyaline fibromatosis syndrome. CASE PRESENTATION: Here, we describe cases of two Sudanese patients, a boy aged 9 months and a girl aged 3.5 years with hypercalcemia as an associated presenting feature of hyaline fibromatosis syndrome. Other features include gingival hypertrophy, painful joint swellings, and restriction of movement, which was misdiagnosed as juvenile rheumatoid arthritis. Workup showed normal phosphate, normal to mildly elevated parathyroid hormone, low vitamin D 25. Genetic testing confirmed the mutation of the ANTXR2/CMG2 gene. Both patients responded well to medical therapy for hypercalcemia, but one of them with the severe form of juvenile hyaline fibromatosis died due to sepsis, while the other one has maintained normocalcemic status. CONCLUSIONS: These cases highlight the rare presentation of this syndrome and reflect the importance of biopsy and genetic testing in reaching the diagnosis, especially when the clinical presentation can mimic other inflammatory bone disorders. Calcium levels should be checked in such cases.

Central precocious puberty in Sudan: 10 years' experience of paediatric endocrinology centres.

Central precocious puberty (CPP) is frequently seen among cases presenting to our endocrine clinics. The purpose of this study was to have base line data on this condition with an attempt to point out any possible unique features of Sudan and to explore challenges faced in management and how that cultural and traditional practices may hamper care. Here, we are reporting the first data on this aspect from Sudanese subjects. Patients labelled as having CPP in Gafaar Ibnauf Children's Hospital and Soba University Hospital Endocrinology Clinics from January 2006 to 2016 are included in a descriptive hospital-based study which was conducted over 10 years in these two main paediatric endocrinology centres. Records of all patients with CPP were reviewed and challenges in diagnosis and management were identified. Most of the children with CPP presented late. Organic causes were more frequent among girls than what has been reported in the literature; in most boys, it was idiopathic. Almost half of the patients with underlying pathology were older than 6 years of age. Most cases including girls have an organic cause, thus magnetic resonance image should be done in all patients. Management of precocious puberty in a resource-limited country is faced with various challenges (e.g., expensive investigations and medications). We suggest establishing a unified protocol for managing these cases and creating collaboration between governmental, nongovernmental organisations and health services.

Clinical profile and aetiologies of delayed puberty: a 15 years' experience from a tertiary centre in Sudan.

OBJECTIVES: Delayed puberty is a common presentation to endocrine clinics, with adult height, sexual capability and fertility being the main concerns for the child and his/her family. Presentation is variable including short stature and/or absence of secondary sexual characteristics. The aetiology can either be constitutional, functional or permanent hypogonadotropic hypogonadism, permanent hypergonadotropic hypogonadism or unclassified. Despite the importance of this subject, there are no publications from Sudan. METHODS: A retrospective hospital-based study. Records of all patients who were seen in the endocrinology unit at Gaffar Ibn Auf Children's Hospital and were diagnosed as having delayed puberty were reviewed and demographic, clinical, and investigations data were obtained. RESULTS: A total of 136 patients were included in this study. Presentation includes short stature in 52.2%, both short stature and delayed puberty in 27.2%, and delayed puberty in 20.6%. The most common aetiologies were permanent hypogonadotropic hypogonadism and functional hypogonadotropic hypogonadism presented in 37.5% and 36% respectively, while constitutional delay of growth and puberty was found in only 14.7%. Type 1 diabetes mellitus (T1DM) was the most frequent chronic illness followed by coeliac disease. Hypergonadotropic hypogonadism was diagnosed in 11.7%, the majority of which were females. CONCLUSIONS: The aetiological pattern reported in this series highlights the role of nutrition and general well-being in pubertal development, as well as the major impact of genetics and consanguinity on disease patterns. Data from African countries are limited and this is the first reported cohort on delayed puberty from Sudan.

Clinical profile, etiology, and diagnostic challenges of primary adrenal insufficiency in Sudanese children: 14-years' experience from a resource limited setting.

OBJECTIVES: Primary adrenal insufficiency (PAI) in children is an uncommon condition. Congenital adrenal hyperplasia (CAH) is the commonest cause followed by autoimmune disorders. Diagnosis and management are challenging especially in resource-limited settings. Studies from Africa are scanty and here we describe for the first time the clinical presentation, possible etiologies, and challenges in diagnosis and management of PAI in a large cohort of Sudanese children. METHODS: This was a descriptive hospital-based study where all patients diagnosed with PAI between 2006 and 2020 were reviewed. The diagnosis was based on clinical presentation, low morning cortisol ± high adrenocorticotropic hormone (ACTH), or inadequate response of cortisol to synacthen stimulation. Challenges faced in diagnosis and management were identified. RESULTS: From 422 PAI suspected patients, 309 (73.2%) had CAH, and 33 (7.8%) had PAI-like symptoms and were not furtherly discussed. Eighty patients (19%) had fulfilled the study criteria: 29 had Allgrove syndrome, nine auto-immune polyendocrinopathy syndrome, seven adrenoleukodystrophy, and one had an adrenal hemorrhage. Hyperpigmentation was the cardinal feature in 75 (93.8%) while the adrenal crisis was not uncommon. Lack of diagnostic facilities has obscured the etiology in 34 (42.5%) patients. CONCLUSIONS: PAI is not uncommon in Sudanese children where genetic causes outweigh the autoimmune ones. Many cases were missed due to nonspecific presentation, lack of awareness, and difficult access to tertiary health care facilities. In addition to the clinical findings, early morning cortisol ± ACTH levels can be used in diagnosis where facilities are limited particularly synacthen stimulation test.

Clinical presentation and molecular genetic analysis of a Sudanese family with a novel mutation in the CYP2R1 gene.

The aim of this study was to identify the genetic basis of two female siblings - born to consanguineous Sudanese parents - diagnosed clinically as having the rare condition of 25-hydroxylase deficiency (vitamin D-dependent rickets type 1B). The initial diagnosis was established based on clinical data, laboratory and radiological findings retrospectively. Primers for all exons (5) of human CYP2R1 (NM_024514) were generated followed by Sanger sequencing on exons 1-5 for both girls and their parents. Homozygosity for a point mutation (c.85C > T) was detected, leading to a nonsynonymous variant at position 29 in exon 1, resulting in a premature stop codon (p.Q29X). This is a previously unknown variant that leads to a severely truncated protein and predicted to be among the 0.1 % most deleterious genomic variants(CADD score 36). To our knowledge, this family represents the first case series from Sudan with a confirmed CYP2R1 gene mutation and the 6th world-wide. With the lack of genetic facilities, diagnosis should be suspected by the persistently low 25 hydroxyvitamin D level in spite of proper treatment and after ruling out liver disease and malabsorption. Patients in this case series showed healing of rickets when treated with high doses of 1,25-dihydroxyvitamin D3 (1,25(OH)D3; calcitriol) and oral calcium.

Aetiologies and clinical patterns of hypopituitarism in Sudanese children.

There is paucity of reported information regarding aetiology and clinical profile of hypopituitarism from resource-limited countries particularly in populations with high rates of consanguineous marriages. Here, we are reporting the first data on this aspect from Sudan. This is a descriptive, retrospective, hospital-based study, carried out in the two main paediatric endocrinology centres in Sudan (Gafaar Ibn Auf Paediatric Tertiary Hospital and Soba University Hospital, Khartoum) from January 2006 up to December 2014. Patients' records were reviewed for relevant demographical, clinical, hormonal and radiological data using pretested study forms. The study included 156 patients. One hundred and one patients were males (M: F = 1.8:1). The commonest age groups were adolescents (57.7%). Consanguinity was found in 77.8% of patients overall and 91% of patients with congenital aetiologies. The commonest clinical presentation was short stature (93.5%). Congenital causes (86.5%) were more prevalent than acquired causes (13.5%). There were six family clusters with multiple pituitary hormone deficiencies (MPHD) and three families with isolated growth hormone (GH) deficiency (IGHD). Most of the congenital cases with MPHD were phenotypic for PROP1 gene mutation (77.5% of sporadic cases and 50% of familial cases). Craniopharyngioma was the commonest of the acquired causes (10.2%). GH was the most frequent hormone deficient (89.7%). Abnormal Magnetic resonance imaging brain findings were significantly seen more in MPHD in comparison to IGHD. The genetic forms of hypopituitarism in populations with high rates of consanguineous marriage like Sudan may be higher than those reported internationally. Molecular genetic studies are, therefore, highly recommended.

Fanconi Bickel syndrome: clinical phenotypes and genetics in a cohort of Sudanese children.

BACKGROUND: Fanconi-Bickel syndrome (FBS) is a rare condition of carbohydrate metabolism, caused by a recessive defect in the facilitative glucose transporter GLUT2 encoded by the SLC2A2 gene and characterized by a wide spectrum of phenotypical features. There is a paucity of reported data on FBS from Sub-Saharan Africa. Here, we describe the clinical, biochemical and genetic characteristics of our patients with FBS from Sudan, a country with a high consanguinity rate. PATIENTS & METHODS: Eleven patients from ten unrelated Sudanese families were included. Clinical & biochemical data were documented and imaging studies done including bone survey and abdominal ultrasound. Liver biopsy was done to confirm the pathological diagnosis in 45% of cases and molecular genetics was performed through contribution with the Exeter genomics laboratory for ten patients. RESULTS: Reported consanguinity was 70% among our patients. Growth was significantly impaired at presentation with mean weights of (-5.3 ± 1.8) SD and heights (-5.4 ± 2.5) SD. Severe chest deformity was present in (27%) and all patients showed features of rickets at presentation. Three patients had neonatal diabetes requiring insulin therapy of which one has been reported before. Six families lost undiagnosed siblings with similar clinical presentations. We identified a total of four homozygous pathogenic SLC2A2 variants in our patients, one of whom had a novel mutation. CONCLUSIONS: FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals' awareness. This is the first series to describe this condition from Sub-Saharan Africa.

Unusual localizations of hydatid cysts: a rare case report from Syria.

Hydatid disease (HD) is an infection with the metacestode stage of the tapeworm Echinococcus. It is commonly seen in South America, The Middle East, Eastern Mediterranean, Africa and China. Hydatid cysts usually affect the liver followed by the lungs. Involvement in other organs has been reported. However, in the majority of the cases, cysts are localized in one organ or one region. We report a rare case of a 36-year-old woman who presented to the hospital in Syria with long-standing history of non-specific abdominal pain. Computerized tomography showed several hydatid cysts in the liver, spleen, left lung, mediastinum (adjacent to the aortic arch), both breasts and above the right gluteal muscles.

Insertion of an Alu Element in Thyroglobulin Gene as a Novel Cause of Congenital Hypothyroidism.

The thyroglobulin (TG) gene encodes a protein required for thyroid hormone synthesis and iodine storage. Deleterious TG mutations produce congenital hypothyroidism (CH) often presenting with undetectable serum TG. Alu elements, common throughout the human genome, have a poly(dA) region in the 3' end of the strand. Herein two of four siblings of a consanguineous Sudanese family with CH, goiter, high initial serum thyrotropin, and undetectable TG were found to have a novel frameshift insertion of an Alu element within an exon of the TG gene: c.7909ins p.Y3637Ffs. This report demonstrates a novel Alu element insertion within TG causing CH.

Increased Prevalence of TG and TPO Mutations in Sudanese Children With Congenital Hypothyroidism.

CONTEXT: Congenital hypothyroidism (CH) is due to dyshormonogenesis in 10% to 15% of subjects worldwide but accounts for 60% of CH cases in the Sudan. OBJECTIVE: To investigate the molecular basis of CH in Sudanese families. DESIGN: Clinical phenotype reporting and serum thyroid hormone measurements. Deoxyribonucelic acid extraction for whole-exome sequencing and Sanger sequencing. SETTING: University research center. PATIENTS: Twenty-six Sudanese families with CH. INTERVENTION: Clinical evaluation, thyroid function tests, genetic sequencing, and analysis. Our samples and information regarding samples from the literature were used to compare TG (thyroglobulin) and TPO (thyroid peroxidase) mutation rates in the Sudanese population with all populations. RESULTS: Mutations were found in dual-oxidase 1 (DUOX1), dual-oxidase 2 (DUOX2), iodotyrosine deiodinase (IYD), solute-carrier (SLC) 26A4, SLC26A7, SLC5A5, TG, and TPO genes. The molecular basis of the CH in 7 families remains unknown. TG mutations were significantly higher on average in the Sudanese population compared with the average number of TG mutations in other populations (P < 0.05). CONCLUSIONS: All described mutations occur in domains important for protein structure and function, predicting the CH phenotype. Genotype prediction based on phenotype includes low or undetectable thyroglobulin levels for TG gene mutations and markedly higher thyroglobulin levels for TPO mutations. The reasons for higher incidence of TG gene mutations include gene length and possible positive genetic selection due to endemic iodine deficiency.

Congenital Hypothyroidism due to Oligogenic Mutations in Two Sudanese Families.

Dyshormonogenic congenital hypothyroidism (CH) generally results from biallelic defects in thyroid hormone synthesis genes. Whole exome sequencing allows easier identification of multiple gene defects. Two Sudanese families with CH resulting from oligogenic defects identified by whole exome sequencing are presented. In family 1, the proposita with CH and goiter was heterozygous for three TPO, one TG, and one DUOX2 mutations, including three novel variants inherited from both parents. In family 2, two brothers with psychomotor delay and goiter were homozygous for digenic mutations in the DUOX2 and DUOX1 genes, while their asymptomatic parents were heterozygous. Accumulation of pathogenic mutations may contribute to CH.

Central Congenital Hypothyroidism Caused by a Novel Mutation, C47W, in the Cysteine Knot Region of TSHß.

BACKGROUND: Isolated central congenital hypothyroidism (ICCH) is a rare form (1:50,000 newborns) of congenital hypothyroidism, which can present with growth and neuropsychological retardation. Unlike the more common primary CH (1:1,500-1:4,000), which presents on newborn screening with elevated serum thyroid-stimulating hormone (TSH) and low thyroxine (T4) and triiodothyronine (T3), ICCH presents with low TSH and low thyroid hormone levels. ICCH, therefore, may be missed in most newborn screens that are based only on elevated TSH. Most cases of ICCH have been associated with mutations in the TSHß gene. PATIENT: We present a consanguineous Sudanese family where the proband was diagnosed with "atypical" CH (serum TSH was low, not high). INTERVENTION AND OUTCOME: The propositus underwent whole-exome sequencing, and the C47W TSHß mutation was identified. Sanger sequencing confirmed the proband to be homozygous for C47W, and both parents were heterozygous for the same mutation. The mutation was predicted by several in silico methods to have a deleterious effect (SIFT 0.0, Damaging; Polyphen2_HDIV 0.973, probably damaging; MutationTaster 1, disease causing; and CADD 3.17, 16.62). C47W affects the first cysteine of the cysteine knot of the TSHß subunit. The cysteine knot region of TSHß is highly conserved across species and is critical for binding to the TSH receptor. Only two other mutations were previously reported along the cysteine knot and showed consistently low or undetectable serum TSH and low T4 and T3 levels. Other TSHß gene mutations causing ICCH have been reported in the "seatbelt" region, necessary for TSHß dimerization with the alpha subunit. CONCLUSIONS: Identification of a mutation in the TSHß gene reinforces the importance of identifying ICCH that can occur in the absence of elevated serum TSH and demonstrates the functional significance of the TSHß cysteine knot.

A Novel Missense Mutation in the SLC5A5 Gene in a Sudanese Family with Congenital Hypothyroidism.

Thyroid hormone synthesis requires the presence of iodide. The sodium-iodide symporter (NIS) is a glycoprotein that mediates the active uptake of iodide from the blood stream into the thyroid grand. NIS defects due to SLC5A5 gene mutations are known to cause congenital hypothyroidism (CH). The proposita is a 28-year-old female whose origin is North Sudan where neonatal screening for CH is not available. She presented with severe constipation and a goiter at the age of 40 days. Laboratory testing confirmed CH, and she was started on levothyroxine. Presumably due to the delayed treatment, the patient developed mental retardation. Her younger sister presented with a goiter, tongue protrusion, and umbilical hernia, and the youngest brother was also diagnosed with CH based on a thyrotropin level >100 µIU/mL at the age of 22 days and 8 days, respectively. The two siblings were treated with levothyroxine and had normal development. Their consanguineous parents had no history of thyroid disorders. Whole-exome sequencing was performed on the proposita. This identified a novel homozygous missense mutation in the SLC5A5 gene-c.1042T>G, p.Y348D-which was subsequently confirmed by Sanger sequencing. All affected children were homozygous for the same mutation, and their unaffected mother was heterozygous. The NIS protein is composed of 13 transmembrane segments (TMS), an extracellular amino-terminus, and an intracellular carboxy-terminus. The mutation is located in the TMS IX, which has the most ß-OH group-containing amino acids (serine and threonine), which is implicated in Na+ binding and translocation. In conclusion, a novel homozygous missense mutation in the SLC5A5 gene was identified in this Sudanese family with CH. The mutation is located in the TMS IX of the NIS protein, which is essential for NIS function. Low iodine intake in Sudan is considered to affect the severity of hypothyroidism in patients.

An uncommon case of chronic myeloid leukemia with variant cytogenetic.

Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by Philadelphia chromosome which is a balanced translocation between chromosome 9 and 22 in 90% of cases. However, variant cytogenetic still happens in 5-10 % of cases, the importance of which is controversial as well as its response to therapy, prognosis and progression to acute leukemias. Here we report a male patient with CML and variant cytogenetic who responded to low dose of Dasatinib (50 mg daily).

Helicobacter pylori infection and the onset of type 1 diabetes mellitus in Sudanese children.

Type 1 diabetes mellitus (T1DM) is a chronic T cell mediated autoimmune disease that results in destruction of pancreatic islet cells. Helicobacter pylori (HP) was recently thought to be a triggering factor for T1DM. This is a prospective case control study at Gaafar Ibnauf Children's Hospital and three other diabetic clinics in Khartoum, during the period January-September 2012. Ninety newly diagnosed T1DM children and a similar number of a control group were compared. Assessment of HP specific serum immunoglobulin was performed using Eliza test. There were 40(44.4%) female and 50(55.6%) male diabetic children. Diabetic children tested positive for HP constituted 56/90 (62.2%) compared to 59/90 (65.6%) from the control group. Diabetic children aged 11-18 years represented 46 (51%), 32/46 (57%) of them were seropositive for HP. A similar number of the same age in control group 30/46 (50.8%) were seropositive. Of 41newly diagnosed diabetic children (44.4%) of newly who complained of symptoms, 30 (53.6%) were seropositive for HP compared to 34 (37.7%) among the healthy children, out of whom 24 (40.7%) tested positive for HP. Diabetic children with moderate anemia were 35 (45.5%) compared to 54 (60.0%) in the control group. Seropositive children for HP in the 2 groups were, respectively, 20(40.8%) and 38(64.4%). Those with a poor family background were 28 (56%), 20 (40.0%) tested positive for HP, compared to 38 (64.4%), of whom 20 (64.5%) were seropositive in the controls. In conclusion, HP infection does not seem to play a role in triggering T1DM in children.

Prevalence of neuropathic pain among patients suffering from chronic low back pain in Saudi Arabia.

OBJECTIVE: The aim of this study was to assess the prevalence of neuropathic pain among patients suffering from chronic low back pain using the Leeds assessment of neuropathic symptoms and signs (LANSS) pain scale. METHODS: This was a pilot study collected from 10 centers in the Middle East Region, with each center enrolling 10 patients between November 2004 and January 2004. In total, 100 patients with chronic low back pain were included in the study. The LANSS clinical assessment score was used to assess the presence of neuropathic pain. Patients with score >12 were considered to have neuropathic pain, while patients with score a < 12 were considered as having nociceptive pain. RESULTS: We found that 41% of the chronic low back pain patients had neuropathic pain and 59% had nociceptive pain. CONCLUSION: The ability to identify neuropathic pain mechanisms should lead to individualized treatment resulting in improved pain control in this group of patients with chronic low back pain.

Adolescent rickets in Saudi Arabia: a rich and sunny country.

In this retrospective study from Saudi Arabia, which is a rich and sunny country, we report our experience with 34 adolescents (20 females, 10 males) with rickets. The commonest cause was vitamin D deficiency (58.8%) followed by rickets due to low calcium intake (11.8%) and genetic causes, including possible 25-hydroxylase deficiency (8.8%). The etiology of nutritional rickets is multifactorial, including lack of sun exposure and inadequate calcium intake. The clinical symptoms were nonspecific and therefore cases in this country are either underdiagnosed or missed. Vitamin D deficient patients needed an average of 19 months of treatment before recovery. High dose vitamin D plus calcium supplementation are recommended for treatment. Measures to prevent rickets in all age groups including adolescents are suggested. Further studies on nutritional and genetic forms of rickets are recommended.

Prevalence of neuropathic pain among patients suffering from chronic low back pain in Saudi Arabia.

OBJECTIVE: The aim of this study was to assess the prevalence of neuropathic pain among patients suffering from chronic low back pain using the Leeds assessment of neuropathic symptoms and signs (LANSS) pain scale. METHODS: This was a pilot study collected from 10 centers in the Middle East Region, with each center enrolling 10 patients between November 2004 and January 2004. In total, 100 patients with chronic low back pain were included in the study. The LANSS clinical assessment score was used to assess the presence of neuropathic pain. Patients with score > or =12 were considered to have neuropathic pain, while patients with score a less than 12 were considered as having nociceptive pain. RESULTS: We found that 41% of the chronic low back pain patients had neuropathic pain and 59% had nociceptive pain. CONCLUSION: The ability to identify neuropathic pain mechanisms should lead to individualized treatment resulting in improved pain control in this group of patients with chronic low back pain.

Cystic fibrosis in Sudanese children: First report of 35 cases.

Cystic fibrosis is the most common severe genetic disorder among children of European descent. It is much less common in Africans and Asians. It affects most critically the lungs causing chronic lung disease, failure to thrive and social deprivation. This is a retrospective review of 35 Sudanese patients with confirmed cystic fibrosis. About 60% of cases presented before the age of 5 years and male to female ratio was 1.7:1.0. Consanguinity was reported in 25 of the families. The main presenting features were productive cough, wheeze and clubbing. The chest X-ray showed variable degrees of hyperinflation, collapse, cystic, fibrotic changes and bronchiectasis involving both upper and lower lobes with blurring of cardiac border and hilar vasculature in the majority of cases. The sweat chloride was between 70 and 140 mmol/l in 83% of the patients (positive > 60 mmol/l). Three patients underwent DNA study and confirmed to have cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. Gene study was not available for the rest of the patients. To our knowledge this is the first report of confirmed cases of cystic fibrosis in Sudanese patients.