Cystic Fibrosis in two Ghanaian Children

Cystic fibrosis (CF) is a severe life-limiting genetic disorder resulting from mutations in the cystic fibrosis transmembrane regulator gene and is reported to be more prevalent among Caucasians than people of African descent. The past three decades have seen a gradual increase in the reporting of CF in non-European populations with CF in all regions including Africa. We report on the first two known Ghanaian children diagnosed with CF presenting early in infancy. The first patient presented with severe acute malnutrition and persistent diarrhea resulting from severe exocrine pancreatic insufficiency. In the second patient, there were recurrent wheeze and recurrent pneumonia, severe dehydration with metabolic alkalosis. Diagnosis of CF in Ghana is challenging due to the absence of diagnostic tools such as sweat testing equipment. In the first patient, sweat testing and genetic testing were done in South Africa. In the second patient, sweat testing was not done but diagnosis was confirmed by genetic testing. Both patients presented with classical CF symptoms including Pseudomonas aeruginosa airway infection before age 6 months. Both children are currently alive and healthy on appropriate treatment. These case reports highlight the growing evidence of CF occurring in people of African descent and the diagnostic challenges faced in Africa.

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Microbial clues lead to a diagnosis of cystic fibrosis in late adulthood

BMJ Case Reports ◽

10.1136/bcr-2019-233470 ◽

2020 ◽

Vol 13 (4) ◽

pp. e233470

Author(s):

Colm Kerr ◽

David Morrissy ◽

Mary Horgan ◽

Barry J Plant

Keyword(s):

Cystic Fibrosis ◽

Genetic Testing ◽

Genetic Disorder ◽

Good Effect ◽

Transmembrane Conductance Regulator ◽

Old Irish ◽

Common Life ◽

Sweat Testing ◽

History Of ◽

Tract Infections

Cystic fibrosis (CF) is the most common life-limiting autosomal recessive genetic disorder among Caucasian populations. The majority of CF cases are diagnosed in childhood; however, increasing numbers of adults are being diagnosed with the condition. We present the case of a 65-year-old Irish woman presenting with a chronic cough and a history of recurrent respiratory tract infections. Staphylococcus aureus, Scedosporium apiospermum and Stenotrophomonas maltophilia were grown from bronchoalveolar lavage raising suspicion for CF. Sweat testing was negative; however, genetic testing revealed the presence of ∆F508 and R117H CF mutations, the latter mutation conferring a milder form of CF. The patient commenced treatment with the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator medication ivacaftor to good effect. Novel CFTR potentiators and modulators have significant potential to benefit morbidity and mortality in this group. In this case, the microbiological results were key in pursuing genetic testing and diagnosing CF.

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Activated L-Arginine/Nitric Oxide Pathway in Pediatric Cystic Fibrosis and Its Association with Pancreatic Insufficiency, Liver Involvement and Nourishment: An Overview and New Results

Journal of Clinical Medicine ◽

10.3390/jcm9062012 ◽

2020 ◽

Vol 9 (6) ◽

pp. 2012

Author(s):

Folke Brinkmann ◽

Beatrice Hanusch ◽

Manfred Ballmann ◽

Sebene Mayorandan ◽

Alexander Bollenbach ◽

...

Keyword(s):

Nitric Oxide ◽

Cystic Fibrosis ◽

High Performance ◽

Genetic Disorder ◽

Pancreatic Insufficiency ◽

Plasma Concentrations ◽

Gas Chromatography Mass Spectrometry ◽

No Production ◽

Healthy Controls ◽

Synthesis Inhibitor

Cystic fibrosis (CF; OMIM 219700) is a rare genetic disorder caused by a chloride channel defect, resulting in lung disease, pancreas insufficiency and liver impairment. Altered L-arginine (Arg)/nitric oxide (NO) metabolism has been observed in CF patients’ lungs and in connection with malnutrition. The aim of the present study was to investigate markers of the Arg/NO pathway in the plasma and urine of CF patients and to identify possible risk factors, especially associated with malnutrition. We measured the major NO metabolites nitrite and nitrate, Arg, a semi-essential amino acid and NO precursor, the NO synthesis inhibitor asymmetric dimethylarginine (ADMA) and its major urinary metabolite dimethylamine (DMA) in plasma and urine samples of 70 pediatric CF patients and 78 age-matched healthy controls. Biomarkers were determined by gas chromatography–mass spectrometry and high-performance liquid chromatography. We observed higher plasma Arg (90.3 vs. 75.6 µM, p < 0.0001), ADMA (0.62 vs. 0.57 µM, p = 0.03), Arg/ADMA ratio (148 vs. 135, p = 0.01), nitrite (2.07 vs. 1.95 µM, p = 0.03) and nitrate (43.3 vs. 33.1 µM, p < 0.001) concentrations, as well as higher urinary DMA (57.9 vs. 40.7 µM/mM creatinine, p < 0.001) and nitrate (159 vs. 115 µM/mM creatinine, p = 0.001) excretion rates in the CF patients compared to healthy controls. CF patients with pancreatic sufficiency showed plasma concentrations of the biomarkers comparable to those of healthy controls. Malnourished CF patients had lower Arg/ADMA ratios (p = 0.02), indicating a higher NO synthesis capacity in sufficiently nourished CF patients. We conclude that NO production, protein-arginine dimethylation, and ADMA metabolism is increased in pediatric CF patients. Pancreas and liver function influence Arg/NO metabolism. Good nutritional status is associated with higher NO synthesis capacity and lower protein-arginine dimethylation.

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Both Exocrine Pancreatic Insufficiency and Signs of Pancreatic Inflammation Are Prevalent in Children with Complicated Severe Acute Malnutrition: An Observational Study

The Journal of Pediatrics ◽

10.1016/j.jpeds.2016.04.013 ◽

2016 ◽

Vol 174 ◽

pp. 165-170 ◽

Cited By ~ 14

Author(s):

Rosalie H. Bartels ◽

Sophie L. Meyer ◽

Tijs A. Stehmann ◽

Céline Bourdon ◽

Robert H.J. Bandsma ◽

...

Keyword(s):

Observational Study ◽

Severe Acute Malnutrition ◽

Pancreatic Insufficiency ◽

Exocrine Pancreatic Insufficiency ◽

Acute Malnutrition

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An analysis of outcomes in children with cystic fibrosis in a tertiary African centre: A retrospective study.

South African Respiratory Journal ◽

10.7196/sarj.2016.v22i2.76 ◽

2016 ◽

Vol 22 (2) ◽

pp. 35

Author(s):

Reratilwe Ephenia Mphahlele ◽

Visva Naidoo ◽

Stanley Amos Thula ◽

Refiloe Masekela

Keyword(s):

South Africa ◽

Cystic Fibrosis ◽

Mutational Analysis ◽

Clinical Laboratory ◽

African Descent ◽

Genetic Disorder ◽

Retrospective Chart Review ◽

Black African ◽

Age Of Diagnosis ◽

The Mean

AbstractBackground: Cystic Fibrosis (CF) is a common genetic disorder in Caucasians that has become increasingly prevalent in populations of African descent. The clinical presentation in African children with CF is commonly related to nutritional and growth abnormalities.Aims/Objectives: To describe clinical, laboratory and spirometric characteristics of children followed up at the CF Clinic at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.Methods: A retrospective chart review of clinical, laboratory and spirometric data of patients registered from January 2013 to January 2016.Results: The data was reviewed for 15 patients mean age 132 months (range 26- 219 months), with 53% males. 60% of these children were Caucasians, 26,7% of these being of black African descent. Collectively, the mean age of diagnosis was 45 months (0- 156), although this was higher in the non-Caucasians at 104 months (range 48-156) versus 1,3 months (range 0-3) in Caucasians. The Caucasian group had better nutritional status when compared to non-Caucasians with BMI of 17,2kg/m2 vs 14,5 kg/m2, respectively. Age at diagnosis had a negative correlation with weight-for-age Z score (-0,61; p < 0.05) and BMI (-0,54; p<0.05). The mean FEV1 % predicted was 70.0 (16,1- 120,2). FEV1% predicted had a positive correlation with both weight z-score (0,83; p < 0.001) and BMI (0.59; p < 0.05). Chronic pseudomonas infection occurred only in 2 patients, both of whom were above the age of 16 years. On mutational analysis 5 of the non-Caucasian patients had no mutations identified on the 30 panel mutation used for testing. phelF508.del was the most commonly identified mutation in Caucasians; with 4 homozygotes and 4 heterozygotes.Conclusion: Cystic fibrosis is diagnosed late in non-Caucasian children in South Africa impacting their growth and lung functions. There is a need for a genetic panel that includes mutations specific for children of African descent.

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Cystic fibrosis: current treatment and future direction

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20211031 ◽

2021 ◽

Vol 10 (4) ◽

pp. 444

Author(s):

Shreya Gupta ◽

Niti Mittal ◽

Mahesh C. Gupta

Keyword(s):

Cystic Fibrosis ◽

Chloride Channels ◽

Genetic Disorder ◽

Pancreatic Insufficiency ◽

Genetic Defect ◽

Disease Process ◽

Holistic Approach ◽

Current Treatment ◽

Cftr Gene ◽

Long Term Effects

Cystic fibrosis is an autosomal recessive genetic disorder, characterized by mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to abnormality in the chloride channels of the mucus and sweat producing glands. Multiple organs systems are affected in this disorder, like respiratory system and gastrointestinal tract, severely impacting the patient’s quality of life, eventually leading on to several complications and death. Since the uncovering of the underlying genetic defect in cystic fibrosis (CF), our knowledge of the disease process has increased substantially, but we still lack a holistic approach to its management, which comprises of multiple facades, requiring both pharmacological and non-pharmacological or rehabilitatory approaches. So far, the therapeutic options were limited to targeting the consequences and complications of the disease, such as respiratory infection, mucus retention, pancreatic insufficiency, etc., but now several promising therapies may be able to address the underlying pathology rather than its long-term effects. This review summarizes the current and upcoming pharmacological options for CF, such as those targeting the CFTR gene defect directly, including gene editing, CFTR correctors and potentiators; drugs targeting the epithelial sodium channels (ENaC inhibitors); repositioning of some existing drugs and evaluating their role in CF; and understanding the disease better by transcriptomic approaches and the role of gut microbiota in the disease process and severity.

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Phenotypic Presentations of Cystic Fibrosis in Children of African Descent

Genes ◽

10.3390/genes12030458 ◽

2021 ◽

Vol 12 (3) ◽

pp. 458

Author(s):

Sophie Mayer Lacrosniere ◽

Michele Gerardin ◽

Laurence Le Clainche-Viala ◽

Veronique Houdouin

Keyword(s):

Cystic Fibrosis ◽

African Descent ◽

Pancreatic Insufficiency ◽

False Negative ◽

False Negative Rate ◽

Exocrine Pancreatic Insufficiency ◽

Sweat Test ◽

North East ◽

The North ◽

Cftr Mutations

The Robert Debre Pediatric Cystic Fibrosis (CF) centre, located in the North East of Paris, a multicultural area, is in charge of a cohort of around a hundred and sixty children diagnosed with CF. Between 2000 and 2019, the proportion of children of African descent in this centre increased from 2% to 10%. We report the clinical features of 17 children of African descent diagnosed with CF: 4 (23%) were diagnosed after a meconium ileus, 14 (83%) had exocrine pancreatic insufficiency, and 7 (41%) had early Pseudomonas aeruginosa infection before the age of two. Even though the majority of patients were diagnosed through NBS, the twenty-nine-mutation testing kit proved less effective in non-Caucasian populations, with a false negative rate of 25% in this series. CF is definitely not solely a Caucasian disease and the literature reveals similar phenotypes in Caucasian and African people provided that they present the same CFTR mutations. Clinicians have to keep in mind that the diagnosis of CF in patients of African descent must be evoked in the case of symptoms and a sweat test must be performed, despite a negative result for NBS.

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