An unusual presentation of neurononopathic gauchers disease.

A six years old male child presented with tremor, ataxia, speech apraxia, supranuclear gaze palsy and hepatosplenomegaly. There was no history of seizures and psycho-cognitive abnormalities. The clinical and bone marrow findings were consistent with Gaucher\u27s disease type 3. KEY WORDS: Gauchers disease, Enzyme replacement therapy, Gene therapy, Bone marrow transplant

Assessing nutritional status of critically Ill patients using serum prealbumin levels

Background: Malnutrition in hospitalized patients, contributes to poor outcomes. Biomarker serum prealbumin, can prevent the complications by commencement of nutritional support to improve clinical outcomes. This study was designed to assess the association between low serum prealbumin level (\u3c18 mg/dl), with length of stay and all cause intensive care unit mortality. Methods: This cross-sectional study was conducted from July 2016 to July 2017 at Aga Khan University Hospital Karachi Pakistan. All consecutive patients, aged between 18 to 70 years, admitted in medical or surgical intensive care unit were included. Demographic, clinical history and blood samples for analysing serum prealbumin were obtained on first day of admission. Patients were categorized into two groups based on their serum prealbumin level (taking \u3c18 mg/dl as low). Results: A total of 139 patients were included in this study; 95 (68.3%) were male. Median (Q3-Q1) prealbumin level of 12.3 mg/dl (18.8–8.7) was observed with low prealbumin level (\u3c18 mg/dl) in 100 (71.9%) patients. All-cause mortality was observed in 26 (26.0%) patients, mortality rate was significantly higher in patients with low prealbumin level (26.0% vs. 17.9%), p-value =0.31). Hospital and intensive care unit length of stay were statistically insignificantly different between the two groups with p-values of 0.27 and 0.44 respectively. Conclusion: We did not find association of low serum prealbumin with length of stay and mortality. Further research is warranted for the assessment of prealbumin as independent predictor of ICU mortality

Perspective on newborn screening (NBS): Evidence sharing on conditions to be included in NBS in Pakistan

Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well established in most developed countries, and all newborns are screened for selected metabolic, endocrine and other disorders based on disease epidemiology, testing and treatment availability, efficiency and cost-effectiveness. Even in developing countries, such screening programmes are initiated using heel prick capillary blood collected on filter paper. The current narrative review was planned to provide a perspective with evidence in favour of starting newborn screening for different disorders. The programme project should be initiated nationwide, taking one disorder, congenital hypothyroidism, as the prototype and a newborn screening panel can then be extended to include other disorders. A task force should be set up to recommend disorders to be included in the panel, develop the national plan policies, and define procedures to strengthen the testing

Unique classification of parathyroid dysfunction in patients with transfusion dependent thalassemia major using nomogram: A cross sectional study

Introduction: Hypoparathyroidism is a rare complication of iron overload in patients with transfusion dependent β thalassemia major (β-TM). We aim to determine the prevalence of parathyroid dysfunction in patients with β-TM. Methods:Diagnosed cases of transfusion dependent β-TM between 5 and 17 years of age were recruited from outpatient clinics of a non-profit organization in Karachi, Pakistan. Blood and urine samples were collected in fasting to determine Ca, P, Alb, Mg, Cr 25OHD and iPTH. Patients were grouped on the basis of upper and lower levels of Ca, 25OHD and iPTH for assessing parathyroid dysfunction into primary hypoparathyroidism [low calcium (Ca) & intact parathyroid hormone (iPTH)], sub-clinical hypoparathyroidism [low iPTH and 25 hydroxy vitamin D (25OHD), low/normal Ca], normal functioning parathyroid gland [Normal Ca, iPTH and 25OHD] and secondary hyperparathyroidism [high iPTH, low/normal Ca and/or 25OHD]. Using PTH nomogram subject specific expected PTH (maxPTH) was calculated. Difference between maxPTH and measured iPTH was determined to assess the utility of nomogram in identifying parathyroid gland dysfunction. The statistical analysis was performed using the Statistical Package of Social Sciences (SPSS) version 20. Results: Median age of patients was 11 years (13-7) with males being 54.2% (n = 205).Based on Ca, 25OHD and iPTH, primary hypoparathyroidism was identified in 3.4% (n = 13) [median iPTH 11.3 pg/ml (12.6-7)], 52.3% (n = 192) had subclinical hypoparathyroidism [iPTH 40.4 pg/ml (52.7-28.7)], and 34% (n = 125) were identified as secondary hyperparathyroidism [iPTH 88.6 pg/ml (116-74.7)]. Normal response to Ca & 25OHD was seen in 10.6% (n = 39) [iPTH 44.2 pg/ml (53.8-33.4)] patients. High phosphorous was present in all groups. Difference between maxPTH & iPTH was highest in primary hypoparathyroidism, followed by subclinical and secondary hyperparathyroidism. Conclusion:Nomogram by Harvey et al. identify low secretion capacity of parathyroid gland that correlated with biochemical classification of patients. It requires clinical validation before using in clinical practice for assessing parathyroid dysfunction

Retrospective study of patients with hyperphenylalaninemia: Experience from a tertiary care center in Pakistan

Objective: To assess the clinical and biochemical features as well as outcome of perphenylalaninemia patients.Methods: The descriptive retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from January 2013 to February 2017 of plasma amino acid analysed at the Biochemical Genetic Laboratory of patients with phenylalanine levels \u3e120 umol/L. Medical charts of patients registered with the Metabolic Clinics were reviewed, while outside referrals were contacted by telephone to collect data on a pre-structured questionnaire. Data was analysed using SPSS 21. Results: Of the 18 patients, 13(72%) were males. Overall median age was 606 days (interquartile range: 761) and median phenylalanine levels were 1280 (interquartile range: 935) umol/L. Phenylalanine hydroxylase deficiency was present in 5(28%) patients while 3(16.6%) had defects in the metabolism or regeneration of tetrahydrobiopterin. The most common clinical features was intellectual deficit and seizures 14(78%) each, followed by lighter hair colour 10(55.5%) and hypotonia 11(61%). High treatment cost was the leading reason for cessation of therapy in 7(39%) followed by refusal by patient\u27s family 5(28%).Conclusion: Most hyperphenylalaninemia cases were diagnosed late when intellectual disability had already developed

Selective screening for organic acidurias and amino acidopathies in Pakistani children

Objective: To determine the frequency of organic acidurais (OA) and amino acidopathies (AA) in selected high-risk patients screened in two years.Study Design: Retrospective Observational study.Place and Duration of Study: The Aga Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014.Methodology: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded. Amino acids and organic acids were analyzed on high performance liquid chromatography and gas chromatography-mass spectrometry respectively. Clinical data and chromatograms of patients screened for IMDs were reviewed by chemical pathologist and metabolic physician.Results: Eighty-eight cases (4.7%) were diagnosed including 41 OA (46.5%), 28 AA (31.8%) and 19 others (21.5%) from 1,866 specimens analyzed. Median age of the patients was 1.1 years, with high consanguinity rate (64.8%). Among OA, methyl CoA mutase deficiency was diagnosed in 9 (10.2%) and was suspected in 2 (2.3%) cases. Five (5.7%) cases of MHBD (2-methyl-3-hydroxybutyryl-CoA), 4 (4.5%) each of PPA (propionic aciduria) and HMG-CoA lyase deficiency, 3 (3.4%) cases each of IVA (isovaleric aciduria), multiple carboxylase deficiency, fructose-1, 6-biphosphatase deficiency, fumarase deficiency, GA-1 (glutaric aciduria type 1) and 2 (2.3%) cases of EMA (ethyl-malonic aciduria). AA included 8 (9.1%) cases of MSUD (maple syrup urine disease), 6 (6.8%) cases of CBS (cystathionine beta-synthetase) and UCDs (urea cycle disorders) each, 5 (5.7%) cases of hyperphenylalaninemia and 3 (3.4%) cases of hyperprolinemia were reported. Other inherited metabolic disorders included: 9 (10.2%) cases of intracellular cobalamin defects, 2 (2.3%) cases each of alkaptonuria, Canavan\u27s disease, SUCL (succinate CoA ligase) deficiency, and 1 (1.1%) case each of DPD (dihydropyrimidine) deficiency, GA-2, NKH (non-ketotic hyperglycinemia), AADC (aromatic amino acid decarboxylase) deficiency.Conclusion: This study presents frequency of OA and AA in the high-risk Pakistani pediatric population analyzed locally

Diagnostic dilemma of patients with methylmalonic aciduria: Experience from a tertiary care centre in Pakistan

Objective: To determine the frequency of disorders leading to methylmalonic acidurias. Methods: This cross-sectional study was conducted from January 2013 to April 2016 at the Aga Khan University Hospital, Karachi, and comprised patients diagnosed with methylmalonic acidurias based on urine organic acid analysis. Clinical history and biochemical data was collected from the biochemical genetics laboratory requisition forms. Organic acid chromatograms of all the subjects were critically reviewed by a biochemical pathologist and a metabolic physician. For assessing the clinical outcome, medical charts of the patients were reviewed. SPSS 19 was used for data analysis. Results: Of the 1,778 patients 50(2.81%) were detected with methylmalonic acidurias. After excluding patients with non-significant peaks of methylmalonic acidemia, 41(2.31%) were included in the final analysis. Of these, 20(48.7%) were females, while the overall median age was 11.5 months (interquartile range: 6-41.5). On stratification by type of disorders leading to methylmalonic acidurias, 9(22%) had methylmalonic acidemia, 12(29%) had Cobalamin-related remethylation disorders, nonspecific methylmalonic acidurias in 16(39%), while 2(5%) each had succinyl coenzyme A synthetase and Vitamin B12 deficiency. respectively. Conclusion: Screening tests, including urine organic acid, provided valuable clues to the aetiology of methylmalonic acidurias

Role of awake prone positioning in patients with moderate-to-severe COVID-19: An experience from a developing country

There is limited evidence on the efficacy of awake prone positioning (PP) in non-ventilated patients with COVID-19 who have hypoxemia. We, therefore, aim to describe our experience with the use of early proning in awake, non-intubated patients with confirmed COVID-19. In our retrospective observational study, 23 patients with confirmed positive PCR test results for Severe Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and hypoxemia that required oxygen therapy with or without non-invasive ventilation were treated with PP. Patients were classified into mild, moderate and severe COVID-19 disease. There were no targeted number of hours for proning per day and patients were kept in prone position according to their tolerance. The primary outcome measure was the avoidance of intubation and secondary outcomes were in-hospital mortality, length of hospital stays and complications related to PP. The mean (standard deviation) age of our cohort was 54.5 (11.7) years, and the majority were males (21/23, 91.3%). Sixty-one per cent (14/23) of the patients were suffering from severe disease and 82.6% (19/23) had bilateral lung involvement with interstitial infiltrates. Majority of the patients were prone positioned for a median of 6 days (IQR 4 - 8). Only one patient required transfer to ICU for mechanical ventilation and subsequently died due to severe ARDS. All 22 patients showed progressive improvement in oxygen requirement and PF ratio, mostly after 3-5 days of proning. The mean length of hospital stay was 12 days. All patients, except one, were discharged in stable conditions, on room air or on a minimal oxygen requirement of 1-2 liters. No major complication of PP was recorded. Awake prone positioning is a valuable and safe therapeutic adjunct that can be applied in patients with moderate-to-severe COVID-19. It can also be included in the home-based management protocols of COVID-19 to improve patient outcomes and mitigate the burden on health care facilities

Genetic Variability through Induced Mutation

The success of plant breeding is based on the accessibility of genetic variation, information about desired traits with well-organized approach that make it likely to develop existing genetic resources. Food security demands to break the yield barrier through increasing new cultivars which can adapt to wide range of environment. It is especially important to observe the character association for yield along with its components before recognizing novel technique to break the yield barrier. There are numerous methods for improved exploiting of the inherent genetic makeup of crops with heritable variations. It is recommended that recognized parental resources can also be induced to mutate for unmasking novel alleles of genes that organize the traits suitable for the crop varieties of the 21st century world. Chemical mutagens have extensively been applied to make genetic changes in crop plants for breeding investigation as well as genetic studies. Ethyl methane sulphonate (EMS) is the most frequently applied as chemical agents in plants. EMS normally induces GC → AT transitions in the genome causing mutated protein that performed different functions rather than normal. It is exposed that the utilization of EMS is an efficient approach for developing novel gene pool