Displaying publications 1 - 20 of 30 in total

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  1. Hussain K, Ismail Z, Sadikun A, Ibrahim P
    Nat Prod Res, 2009;23(3):238-49.
    PMID: 19235024 DOI: 10.1080/14786410801987597
    Ethanol and aqueous extracts of the different parts of Piper sarmentosum were analysed by HPLC for marker compounds to standardise these extracts. The standardised extracts were investigated for antioxidant activity (beta-carotene linoleate model and DPPH model), anti-TB activity (microplate tetrazolium assay), and estimation of total phenolic and amide contents. The extracts of the different parts exhibited different antioxidant activity, phenolic and amide contents (p < 0.01). The ethanol extracts exhibited better antioxidant activity as compared to the aqueous extracts. The leaf ethanol extract was further investigated for dose response relationship and its EC(50) was found to be 38 microg mL(-1). All the extracts have exhibited anti-TB activity with MIC/MBC 12.5 microg mL(-1). The leaf methanol extract was fractionated and the ethyl acetate fraction exhibited anti-TB activity with MIC/MBC 3.12 microg mL(-1) while MIC/MBC of isoniazid (INH) was found to be 0.5 microg mL(-1). A positive correlation was found between antioxidant activity and total polyphenols, flavonoids and amides, in the beta-carotene linoleate model (p = 0.05) and in the DPPH model (p = 0.01). The analytical method was found to have linearity >0.9922, coefficient of variance <5% and accuracy 95.5 +/- 5 to 96.9 +/- 5. This plant possesses promising antioxidant as well as anti-TB properties.
  2. Hussain K, Ismail Z, Sadikun A, Ibrahim P
    Planta Med, 2010 Mar;76(5):418-25.
    PMID: 19862670 DOI: 10.1055/s-0029-1186279
    The present study aimed to investigate standardized ethanol extracts of fruit and leaves of Piper sarmentosum for their in vivo antioxidant activity in rats using a CCl (4)-induced oxidative stress model. The standardization was based on the quantification of the markers pellitorine, sarmentine and sarmentosine by high performance liquid chromatography (HPLC), and determination of total primary and secondary metabolites. The rats, divided into 7 groups each (n = 6), were used as follows: group 1 (CCl (4), negative control), group 2 (untreated, control), groups 3 and 4 (fruit extract 250 and 500 mg/kg, respectively), groups 5 and 6 (leaf extract 250 and 500 mg/kg, respectively) and group 7 (vitamin-E 100 mg/kg, positive control). The doses were administered orally for 14 days; 4 h following the last dose, a single dose of CCl (4) (1.5 mg/kg) was given orally to all the groups except group 2, and after 24 h, blood and liver of each animal were obtained. Analysis of plasma and liver homogenate exhibited significant preservation of markers of antioxidant activity, total plasma antioxidant activity (TPAA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive species (TBARS), in the pretreated groups as compared to the CCl (4) group (p < 0.05). Histology of the liver also evidenced the protection of hepatocytes against CCl (4) metabolites in the pretreated groups. The results of this study indicate the IN VIVO antioxidant activity of both extracts of the plant, which may be valuable to combat diseases involving free radicals.
  3. Hussain K, Ismail Z, Sadikun A, Ibrahim P
    PMID: 19770264 DOI: 10.1093/ecam/nep143
    In vitro assays are economical and easy to perform but to establish relevance of their results to real clinical outcome in animals or human, pharmacokinetics is prerequisite. Despite various in vitro pharmacological activities of extracts of Piper sarmentosum, there is no report of pharmacokinetics. Therefore, the present study aimed to evaluate ethanol extract of fruit of the plant in dose of 500 mg kg(-1) orally for pharmacokinetics. Sprague-Dawley rats were randomly divided into groups 1, 2, and 3 (each n = 6) to study absorption, distribution and excretion, respectively. High performance liquid chromatography (HPLC) with ultraviolet detection was applied to quantify pellitorine, sarmentine and sarmentosine in plasma, tissues, feces and urine to calculate pharmacokinetic parameters. Pellitorine exhibited maximum plasma concentration (C(max)) 34.77 ng mL(-1) ± 1.040, time to achieve C(max) (T(max)) 8 h, mean resident time (MRT) 26.00 ± 0.149 h and half life (t(1/2)) 18.64 ± 1.65 h. Sarmentine showed C(max) 191.50 ± 12.69 ng mL(-1), T(max) 6 h, MRT 11.12 ± 0.44 h and t(1/2) 10.30 ± 1.98 h. Sarmentosine exhibited zero oral bioavailability because it was neither detected in plasma nor in tissues, and in urine. Pellitorine was found to be distributed in intestinal wall, liver, lungs, kidney, and heart, whereas sarmentine was found only in intestinal wall and heart. The cumulative excretion of pellitorine, sarmentine and sarmentosine in feces in 72 h was 0.0773, 0.976, and 0.438 μg, respectively. This study shows that pellitorine and sarmentine have good oral bioavailability while sarmentosine is not absorbed from the gastrointestinal tract.
  4. Hussain K, Majeed MT, Ismail Z, Sadikun A, Ibrahim P
    South Med Rev, 2009 Apr;2(1):19-23.
    PMID: 23093874
  5. Salman M, Mustafa ZU, Khan TM, Shehzadi N, Hussain K
    Disaster Med Public Health Prep, 2020 Jun;14(3):e44-e45.
    PMID: 32662386 DOI: 10.1017/dmp.2020.247
  6. Zia S, Saleem M, Asif M, Hussain K, Butt BZ
    Inflammopharmacology, 2022 Dec;30(6):2211-2227.
    PMID: 36223063 DOI: 10.1007/s10787-022-01048-1
    Rheumatoid arthritis is a chronic inflammatory disorder of polyarticular tissues, characterised by progressive synovitis. Its prolonged treatment imparts a huge burden on the healthcare system and results in toxicity, which necessitates the search for safe, efficacious and cost-effective therapies. Diospyros malabarica (Desr.) Kostel is traditionally used for anti-inflammatory purposes; however, to the best of our knowledge, there is no detailed study reporting the in vivo anti-inflammatory potential of this plant. Therefore, in the current study, the methanol extract of D. malabarica (Desr.) Kostel fruit (mDMF) was evaluated for its antioxidant, anti-inflammatory and anti-arthritic potentials, along with its underlying mechanisms. The antioxidant activity was evaluated by DPPH assay. Total phenolic and flavonoid contents were estimated via colorimetric and high-performance liquid chromatography (HPLC) methods. Different doses (250, 500 and 750 mg/kg) of mDMF were used to evaluate the anti-inflammatory and anti-arthritis actions in acute inflammatory (carrageenan and histamine-induced paw oedema) and Freund's complete adjuvant (FCA)-induced arthritis rat models. Levels of various pro- and anti-inflammatory biomarkers were estimated using ELISA and RT-PCR techniques. Paw samples were used for different histopathological and radiographic studies. Qualitative phytochemical and HPLC analyses indicated the presence of various polyphenolic compounds in mDMF, which exhibited marked antioxidant activity in the DPPH assay. mDMF showed time-dependent anti-inflammatory and anti-arthritic effects in in vivo models. ELISA assay data showed significant (p 
  7. Shehzadi N, Hussain K, Khan MT, Salman M, Islam M
    Pak J Pharm Sci, 2017 Sep;30(5):1767-1777.
    PMID: 29084700
    The absence of chromophore and/or conjugated system, prerequisite for UV and florescent light detection, or absorbance at very low wavelength necessitates the development of simple and reliable methods for the determination of amikacin sulphate. Therefore, the present study describes for the first time dynamics of the drug derivatization using ninhydrin reagent and development and validation of a simple RP-HPLC method, using diode array detector (DAD). The variables such as heating time, heating type, drug-reagent ratio, reagent composition and storage temperature of the derivative were optimized. The analyte and aqueous ninhydrin solution upon heating for 2.00-5.00 min produced the colored drug-derivative which was stable for one month at refrigeration. The derivatized drug (20.00μL) was eluted through a column - Eclipse DB-C18 (5.00 µm, 4.60×150.00 mm), maintained at 25°C- using isocratic mobile phase comprising water and acetonitrile (70:30, v/v) at a flow rate of 1.00 mL/min, and detected at 400 nm. The method was found to be reliable (98.08-100.72% recovery), repeatable (98.02-100.72% intraday accuracy) and reproducible (98.47-101.27% inter day accuracy) with relative standard deviation less than 5%. The results of the present study indicate that the method is easy to perform, specific and sensitive, and suitable to be used for the determination of amikacin sulphate in bulk and pharmaceutical preparations using less expensive/laborious derivatization.
  8. Umair Khan M, Ahmad A, Hussain K, Salam A, Hasnain ZU, Patel I
    PMID: 26072905 DOI: 10.3352/jeehp.2015.12.27
    In Pakistan, courses in pharmacy practice, which are an essential component of the PharmD curriculum, were launched with the aim of strengthening pharmacy practice overall and enabling pharmacy students to cope with the challenges involved in meeting real-world healthcare needs. Since very little research has assessed the efficacy of such courses, we aimed to evaluate students' perceptions of pharmacy practice courses and their opinions about whether their current knowledge of the topics covered in pharmacy practice courses is adequate for future practice.
  9. Umair Khan M, Ahmad A, Ejaz A, Ata Rizvi S, Sardar A, Hussain K, et al.
    PMID: 26072906 DOI: 10.3352/jeehp.2015.12.28
    PURPOSE: The goal of this study was to compare the knowledge and attitudes of pharmacy and medical students regarding adverse drug reactions (ADRs), as well as their perceptions of barriers to ADR reporting, in a Higher Education Commission-recognised Pakistani university.
    METHODS: A cross-sectional study was conducted among final-year pharmacy (n=91) and medical (n=108) students in Pakistan from June 1 to July 31, 2014. A self-administered questionnaire was used to collect the data. The responses of pharmacy students were compared to those of medical students.
    RESULTS: Pharmacy students had a significantly better knowledge of ADRs than medical students (mean±SD, 5.61±1.78 vs. 3.23±1.60; P<0.001). Gender showed a significant relationship to knowledge about ADRs, and male participants were apparently more knowledgeable than their female counterparts (P<0.001). The attitudes of pharmacy students regarding their capability to handle and report ADRs were significantly more positive than those of medical students (P<0.05). In comparison to pharmacy students, a lack of knowledge of where and how to report ADRs was the main barrier that medical students perceived to ADR reporting (P=0.001).
    CONCLUSION: Final-year pharmacy students exhibited more knowledge about ADRs and showed more positive attitudes regarding their capacity to handle and report ADRs than final-year medical students.
    KEYWORDS: Comparison; Medical; Pakistan; Pharmacovigilance; Pharmacy; Students
  10. Salman M, Khan AH, Syed Sulaiman SA, Hughes JD, Khan JH, Shehzadi N, et al.
    J Pak Med Assoc, 2021 May;71(5):1384-1387.
    PMID: 34091619 DOI: 10.47391/JPMA.1162
    Objective: To investigate the prevalence and severity of lower urinary tract symptoms among calcium channel blocker users, and the impact on patients' quality of life.

    METHODS: The cross-sectional study was conducted at one hospital and 2 community pharmacies in Lahore, Pakistan, from November 2017 to July 2018, and comprised patients using calcium channel blockers. Data was collected using standardised scales to assess lower urinary tract symptoms and quality of life. Data was analysed using SPSS 22.

    RESULTS: Of the 410 subjects, 315 (76.8%) were males. The overall median age was 50.84 years, IQR 19 with 126 (30.7%) aged 41-50 years. Of the total, 108 (26.3%) patients were on calcium channel blockers alone, while the rest were taking it in combination with other drugs. Prevalence of lower urinary tract symptoms was 307 (74.9%); mild 103 (25.1%), moderate 201 (49.1%) and severe 106 (25.9%). The symptoms were significantly associated with reduced quality of life (p<0.05).

    Conclusion: Majority calcium channel blockers users had clinically significant lower urinary tract symptoms which significantly reduced patients' quality of life.

  11. Salman M, Khan AH, Sulaiman SAS, Hughes J, Khan JH, Hussain K
    Turk J Urol, 2018 Jul;44(4):335-340.
    PMID: 29932403 DOI: 10.5152/tud.2018.44834
    OBJECTIVE: The objective of the current study was to develop an Urdu version of the International Prostate Symptom Score (IPSS-U) and validate it for Pakistani patients suffering from lower urinary tract symptoms (LUTS).
    MATERIAL AND METHODS: IPSS-U was developed by a two-step forward and back translation and to evaluate its psychometric properties, a prospective study involving patients suffering from LUTS (n=267) was conducted at Outpatient Urology Department, Mayo Hospital, Lahore, Pakistan. Internal consistency and reproducibility were assessed using Cronbach's alpha and the Intra-Class Correlation Coefficient (ICC). Moreover, exploratory, and confirmatory factor analyses were performed to determine dimensionality of IPSS-U items.
    RESULTS: Overall reliability of IPSS-U was satisfactory (Cronbach's alpha=0.72, ICC of symptom questions=0.92 and ICC of QOL index=0.75). Exploratory factor analysis revealed that two factors were consistent, which together explained 59.8% of the variance. IPSS-U items 1, 3, 5 and 6 were components of the first factor whereas item 2, 4 and 7 were components of the second factor. All the items loaded high on their factors and there were no cross loadings. Moreover, confirmatory factor analysis also showed two-factor model, with acceptable fitting patterns.
    CONCLUSION: IPSS-U is a valid and reliable non-gender specific instrument to assess the frequency and severity of LUTS in Urdu-speaking population.
  12. Latif A, Hussain K, Shehzadi N, Islam M, Khan MT, Anwar R, et al.
    Pharm Biol, 2017 Dec;55(1):547-553.
    PMID: 27951746
    CONTEXT: Kanji, a liquid preparation of roots of Daucus carota L. ssp. sativus (Hoffm.) Arcang. var. vavilovii Mazk. (Apiaceae), may inhibit glutathione sulfotransferase (GST) activity due to ferulic acid content.

    OBJECTIVES: GST inhibition activity and characterization of Kanji and methanol extract of D. carota roots, and oral absorption pattern of ferulic acid from Kanji in rats.

    MATERIALS AND METHODS: GST inhibition activity of Kanji and methanol extract of D. carota roots in concentration range 0.001-100.00 mg/mL was determined using Sprague Dawley rat liver cytosolic fraction. Methanol extract upon column chromatography gave ferulic acid, which was used to characterize Kanji and determine its oral absorption pattern in Wistar rats.

    RESULTS: The GST inhibition activity of Kanji (100.00 μg/mL), methanol extract of D. carota roots (100.00 μg/mL) and tannic acid (10.00 μg/mL, positive control) was found to be 0.162 ± 0.016, 0.106 ± 0.013 and 0.073 ± 0.004 μM/min/mg, respectively. Different Kanji samples and methanol extract contained ferulic acid (0.222-0.316 mg/g) and 0.77 mg/g, respectively. Ferulic acid did not appear in plasma after oral administration of Kanji.

    DISCUSSION: Kanji having solid contents 80.0 μg/mL, equivalent to 0.0025 μg/mL ferulic acid, does not inhibit the activity of GST. The oral administration of Kanji, in human equivalent dose (528 mg/kg, 16.67 μg ferulic acid), to rats indicated poor absorption of ferulic acid.

    CONCLUSION: Kanji having solid contents 14-36 mg/mL does not inhibit GST activity, hence may not interfere with drugs that are the substrates of GST, if taken concomitantly.

  13. Balasubramaniam S, Kapoor R, Yeow JH, Lim PG, Flanagan S, Ellard S, et al.
    J Pediatr Endocrinol Metab, 2011;24(7-8):573-7.
    PMID: 21932603
    Hyperinsulinism-hyperammonemia syndrome (HI/HA) (OMIM 606762), the second most common form of congenital hyperinsulinism (CHI) is associated with activating missense mutations in the GLUD1 gene, which encodes the mitochondrial matrix enzyme, glutamate dehydrogenase (GDH). Patients present with recurrent symptomatic postprandial hypoglycemia following protein-rich meals (leucine-sensitive hypoglycemia) as well as fasting hypoglycemia accompanied by asymptomatic elevations of plasma ammonia. In contrast to other forms of CHI, the phenotype is reported to be milder thus escaping recognition for the first few months of life. Early diagnosis and appropriate management are essential to avoid the neurodevelopmental consequences including epilepsy and learning disabilities which are prevalent in this disorder. We report an infant presenting with afebrile seizures secondary to hyperinsulinemic hypoglycemia resulting from a novel de novo mutation of the GLUD1 gene.
  14. Ibraheem M, Butt F, Waqas RM, Hussain K, Tufail RF, Ahmad N, et al.
    Materials (Basel), 2021 Nov 15;14(22).
    PMID: 34832298 DOI: 10.3390/ma14226890
    The purpose of this research is to study the effects of quarry rock dust (QRD) and steel fibers (SF) inclusion on the fresh, mechanical, and microstructural properties of fly ash (FA) and ground granulated blast furnace slag (SG)-based geopolymer concrete (GPC) exposed to elevated temperatures. Such types of ternary mixes were prepared by blending waste materials from different industries, including QRD, SG, and FA, with alkaline activator solutions. The multiphysical models show that the inclusion of steel fibers and binders can enhance the mechanical properties of GPC. In this study, a total of 18 different mix proportions were designed with different proportions of QRD (0%, 5%, 10%, 15%, and 20%) and steel fibers (0.75% and 1.5%). The slag was replaced by different proportions of QRD in fly ash, and SG-based GPC mixes to study the effect of QRD incorporation. The mechanical properties of specimens, i.e., compressive strength, splitting tensile strength, and flexural strength, were determined by testing cubes, cylinders, and prisms, respectively, at different ages (7, 28, and 56 days). The specimens were also heated up to 800 °C to evaluate the resistance of specimens to elevated temperature in terms of residual compressive strength and weight loss. The test results showed that the mechanical strength of GPC mixes (without steel fibers) increased by 6-11%, with an increase in QRD content up to 15% at the age of 28 days. In contrast, more than 15% of QRD contents resulted in decreasing the mechanical strength properties. Incorporating steel fibers in a fraction of 0.75% by volume increased the compressive, tensile, and flexural strength of GPC mixes by 15%, 23%, and 34%, respectively. However, further addition of steel fibers at 1.5% by volume lowered the mechanical strength properties. The optimal mixture of QRD incorporated FA-SG-based GPC (QFS-GPC) was observed with 15% QRD and 0.75% steel fibers contents considering the performance in workability and mechanical properties. The results also showed that under elevated temperatures up to 800 °C, the weight loss of QFS-GPC specimens persistently increased with a consistent decrease in the residual compressive strength for increasing QRD content and temperature. Furthermore, the microstructure characterization of QRD blended GPC mixes were also carried out by performing scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive spectroscopy (EDS).
  15. Salman M, Khan AH, Adnan AS, Sulaiman SA, Hussain K, Shehzadi N, et al.
    Rev Assoc Med Bras (1992), 2016 Nov;62(8):742-747.
    PMID: 27992014 DOI: 10.1590/1806-9282.62.08.742
    Objective:: Anemia, a common complication of chronic kidney diseases (CKD), is involved in significant cardiovascular morbidity. Therefore, the objective of our study was to investigate the prevalence and severity of anemia in pre-dialysis patients, as well as to determine the predictors of anti-anemic therapy.

    Method:: A retrospective, observational study was conducted on adult pre-dialysis patients receiving treatment at the Hospital Universiti Sains Malaysia from January 2009 to December 2013.

    Results:: A total of 615 eligible cases were included. The mean age of patients was 64.1±12.0 years. The prevalence of anemia was 75.8%, and the severity of anemia was mild in 47.7% of the patients, moderate in 32.2%, and severe in 20%. Based on morphological classification of anemia, 76.9% of our patients had normochromic-normocytic anemia whereas 21.8 and 1.3% had hypochromic-microcytic anemia and macrocytic anemia, respectively. Oral iron supplements were prescribed to 38.0% of the patients and none of the patients was given erythropoietin stabilizing agents (ESA) or intravenous iron preparations. In logistic regression, significant predictors of anti-anemic preparation use were decreased hemoglobin and hematocrit, and advanced stages of CKD.

    Conclusion:: The results of the present study suggest that the prevalence of anemia in pre-dialysis patients is higher than currently accepted and it is found to be correlated with renal function; prevalence increases with declined renal function. An earlier identification as well as appropriate management of anemia will not only have a positive impact on quality of life but also reduce hospitalizations of CKD patients due to cardiovascular events.

  16. Salman M, Khan AH, Syed Sulaiman SA, Khan JH, Hussain K, Shehzadi N
    Biomed Res Int, 2017;2017:4269875.
    PMID: 29124064 DOI: 10.1155/2017/4269875
    Background: Numerous medications are known to be associated with the development of lower urinary tract symptoms (LUTS). One such medication group is calcium channel blockers (CCB).

    Objective: To critically examine the literature regarding the involvement of CCB in manifestation of LUTS in humans.

    Methods: A systematic literature search was conducted on PubMed, SciELO, Scopus, and OpenGrey databases to find all potentially relevant research studies before August 2016.

    Results: Five studies met the inclusion criteria and were included in this review. Three out of five studies stated that CCB were involved in either precipitation or exacerbation of LUTS. As for the remaining two studies, one study found out that only the monotherapy of CCB was associated with increased prevalence of nocturia and voiding symptoms in young females, whereas the other study reported an inverse association of CCB with LUTS. The methodological quality of studies was considered high for four studies and low for one study.

    Conclusion: Healthcare providers should make efforts for an earlier identification of the individuals at risk of LUTS prior to the commencement of CCB therapy. Moreover, patients should be counselled to notify their healthcare provider if they notice urinary symptoms after the initiation of CCB.

  17. Riskhan B, Safuan HAJ, Hussain K, Elnour AAH, Abdelmaboud A, Khan F, et al.
    Sensors (Basel), 2023 Jul 21;23(14).
    PMID: 37514868 DOI: 10.3390/s23146574
    Cyberattacks in the modern world are sophisticated and can be undetected in a dispersed setting. In a distributed setting, DoS and DDoS attacks cause resource unavailability. This has motivated the scientific community to suggest effective approaches in distributed contexts as a means of mitigating such attacks. Syn Flood is the most common sort of DDoS assault, up from 76% to 81% in Q2, according to Kaspersky's Q3 report. Direct and indirect approaches are also available for launching DDoS attacks. While in a DDoS attack, controlled traffic is transmitted indirectly through zombies to reflectors to compromise the target host, in a direct attack, controlled traffic is sent directly to zombies in order to assault the victim host. Reflectors are uncompromised systems that only send replies in response to a request. To mitigate such assaults, traffic shaping and pushback methods are utilised. The SYN Flood Attack Detection and Mitigation Technique (SFaDMT) is an adaptive heuristic-based method we employ to identify DDoS SYN flood assaults. This study suggested an effective strategy to identify and resist the SYN assault. A decision support mechanism served as the foundation for the suggested (SFaDMT) approach. The suggested model was simulated, analysed, and compared to the most recent method using the OMNET simulator. The outcome demonstrates how the suggested fix improved detection.
  18. Rehman FU, Gyamfi S, Rasool SF, Akbar F, Hussain K, Prokop V
    Environ Sci Pollut Res Int, 2023 Dec;30(58):122274-122292.
    PMID: 37964150 DOI: 10.1007/s11356-023-30956-0
    Recently, the trend of circular economy innovation (CEI) drive SMEs to initiate more sustainable practices to attain market competitiveness but rare attention has been paid in emerging economies. Hence, this study plans to explore the impacts of CEI on the triple bottom lines (TBL) efficiencies in the light of market competitiveness among the production SMEs in emerging economies. The study complied data by using a survey-based technique in Pakistan, Malaysia, and China. With a sample of 306 for each segment, data were evaluated with PLS-SEM to clarify results. The findings reveal that CEI has positive significant effects on the market competitiveness and TBL efficiencies among the production SMEs in emerging economies. The findings also clarify that market competitiveness mediates the relationship between CEI and the TBL efficiencies. The findings elaborate the theoretical foundations for environmental-based production SMEs to formulate more sustainable strategies in the light of CEI to gain market competitiveness. It also clarifies the understandings of policy makers and environmental regulators by providing a novel precursor to frame the environment-based TBL guidelines for SMEs. It adds to the UN sustainability agenda by elevating the role of CEI as a novel domain among emerging economies grounded on the resource-based view theory.
  19. Laver TW, Wakeling MN, Hua JHY, Houghton JAL, Hussain K, Ellard S, et al.
    Clin Endocrinol (Oxf), 2018 Nov;89(5):621-627.
    PMID: 30238501 DOI: 10.1111/cen.13841
    OBJECTIVE: Hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or more rarely feature as part of a syndrome. Screening for mutations in the "syndromic" HH genes is guided by phenotype with genetic testing used to confirm the clinical diagnosis. As HH can be the presenting feature of a syndrome, it is possible that mutations will be missed as these genes are not routinely screened in all newly diagnosed individuals. We investigated the frequency of pathogenic variants in syndromic genes in infants with HH who had not been clinically diagnosed with a syndromic disorder at referral for genetic testing.

    DESIGN: We used genome sequencing data to assess the prevalence of mutations in syndromic HH genes in an international cohort of patients with HH of unknown genetic cause.

    PATIENTS: We undertook genome sequencing in 82 infants with HH without a clinical diagnosis of a known syndrome at referral for genetic testing.

    MEASUREMENTS: Within this cohort, we searched for the genetic aetiologies causing 20 different syndromes where HH had been reported as a feature.

    RESULTS: We identified a pathogenic KMT2D variant in a patient with HH diagnosed at birth, confirming a genetic diagnosis of Kabuki syndrome. Clinical data received following the identification of the mutation highlighted additional features consistent with the genetic diagnosis. Pathogenic variants were not identified in the remainder of the cohort.

    CONCLUSIONS: Pathogenic variants in the syndromic HH genes are rare; thus, routine testing of these genes by molecular genetics laboratories is unlikely to be justified in patients without syndromic phenotypes.

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