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Plasma renin activity is an important investigation to differentiate the causes, and would be suppressed in 17OHD by the potent mineralocorticoid activity, and is high in renovascular disease.6 On the contrary, aldosterone level could be suppressed, normal or raised in 17OHD.2 4 5 Low aldosterone level arises as a result of a suppressed renin angiotensin system while high level might be related to more severe enzyme defects resulting in greater production of end product from aldosterone precursors.4 As 17OHD has a characteristic pattern of metabolite excretion and metabolite ratios on urine steroid profiling, this profiling is an important investigation when diagnosing the condition. The use of glucocorticoid would decrease the adrenocorticotropic hormone drive and production of deoxycorticosterone and corticosterone, which would facilitate improved blood pressure control and electrolyte balance.2 Different forms and dosages of glucocorticoid replacement have been described in the literature, ranging from dexamethasone 0.25 mg to 1 mg daily, or equivalent.2 4 5 In some cases, an antihypertensive agent with a mineralocorticoid antagonist effect such as spironolactone or eplerenone may be required for blood pressure control.3 5 Patients may develop end organ damage such as hypertensive retinopathy if blood pressure control is suboptimal.2 Deoxycorticosterone and corticosterone levels might not be normalised despite treatment. To date, the Human Gene Mutation Database has reported [greater than]100 different types of mutations on the CYP17A1 gene.7Genetic analysis showed compound heterozygous pathogenic variants in the CYP17A1 gene (reference transcript: [...]17OHD should be considered in a young hypertensive individual with hypokalaemia.

As a prototype of genomics-guided precision medicine, individualized thiopurine dosing based on pharmacogenetics is a highly effective way to mitigate hematopoietic toxicity of this class of drugs. Recently, NUDT15 deficiency was identified as a genetic cause of thiopurine toxicity, and NUDT15-informed preemptive dose reduction was quickly adopted in clinical settings. To exhaustively identify pharmacogenetic variants in this gene, we developed massively parallel NUDT15 function assays to determine the variants’ effect on protein abundance and thiopurine cytotoxicity. Of the 3,097 possible missense variants, we characterized the abundance of 2,922 variants and found 54 hotspot residues atwhich variants resulted in complete loss of protein stability. Analyzing 2,935 variants in the thiopurine cytotoxicity-based assay, we identified 17 additional residues where variants altered NUDT15 activity without affecting protein stability. We identified structural elements key to NUDT15 stability and/or catalytical activity with single amino acid resolution. Functional effects for NUDT15 variants accurately predicted toxicity risk alleles in patients treated with thiopurines with far superior sensitivity and specificity compared to bioinformatic prediction algorithms. In conclusion, our massively parallel variant function assays identified 1,152 deleterious NUDT15 variants, providing a comprehensive reference of variant function and vastly improving the ability to implement pharmacogenetics-guided thiopurine treatment individualization.

No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme. We retrieved the demographics of the screened newborns and the screening results from July 2013 to July 2016. These data were used to calculate quality metrics such as call-back rate and false-positive rate. Clinical details of true-positive and false-negative cases and their outcomes were described. Finally, the call-back logistics for newborns with positive screening results were reviewed. During the study period, 30 448 newborns referred from 13 private and public units were screened. Of the samples, 98.3% were collected within 7 days of life. The overall call-back rate was 0.128% (39/30 448) and the false-positive rate was 0.105% (32/30 448). Six neonates were confirmed to have inborn errors of metabolism, including two cases of medium-chain acyl-coenzyme A dehydrogenase deficiency, one case of carnitine-acylcarnitine translocase deficiency, and three milder conditions. One case of maternal carnitine uptake defect was diagnosed. All patients remained asymptomatic at their last follow-up. The Centre of Inborn Errors of Metabolism has established a comprehensive expanded newborn screening programme for selected inborn errors of metabolism. It sets a standard against which the performance of other private newborn screening tests can be compared. Our experience can also serve as a reference for policymakers when they contemplate establishing a government-funded universal expanded newborn screening programme in the future.

[...]she was prescribed thyroxine replacement and her TSH was normalised (3.28 mIU/L) by June 2014. [...]testing in both patients for FDH targeting exon 7 of the ALB gene (OMIM *103600; Refseq NG_009291.1/NM_000477.6/NP_000468.1) showed heterozygous c.725G[greater than]A p.(Arg242His), a reported pathogenic variant in Chinese.1 Discussion Familial dysalbuminaemic hyperthyroxinaemia is an autosomal dominant condition caused by variants of albumin, the gene product of ALB.2 The prevalence of FDH has been estimated to be 0.01% in Caucasian populations but much higher (1.0%-1.8%) in Hispanic populations.3 The prevalence is uncertain in East Asian populations. [...]any previous thyroid function results should be reviewed. For FDH, it is important to note the assay platform used (hinted by the reference intervals provided), as a change of assay from one that is less affected by FDH to one that is prone to interference in FDH may give the clinician a false sense of an acquired condition. [...]the TSH level in patients with FDH should be normal unless due to thyroid-related treatment, or genuine pituitary or thyroid disease.

Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: and for long QT syndrome; for Brugada syndrome; for catecholaminergic polymorphic ventricular tachycardia; and for hypertrophic cardiomyopathy; for dilated cardiomyopathy; and and for arrhythmogenic right ventricular dysplasia/cardiomyopathy. There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in (NM_198056.2:c.429del and c.2024-11T>A), two in (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in (NM_170707.3:c.73C>A and c.1209_1213dup). We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

Blood and urine test results of the patient Renal biopsy was repeated and revealed mild-to-moderate global mesangial cell proliferation and a few clusters of arterioles showing hyaline arteriolosclerosis with a peripheral and segmental distribution (Fig). Figure. (a) Representative glomerulus showing mesangial proliferative glomerulonephritis pattern of changes with lobular accentuation of glomerulartuft and mild global mesangial cellular proliferation and thickened capillary wall (periodic acid[-]Schiff stain, original magnification [x]400). (b)Representative glomerulus showing mesangial proliferative glomerulonephritis pattern of changes with lobular accentuation of glomerular tuft andmild global mesangial cellular proliferation and tram-track split capillary wall (arrow) [methenamine silver stain, original magnification [x]400]. (c)Occasional glomerulus showing evidence of mesangiolysis evident by loss of argyrophilic mesangial material on the right part of the glomerulus.Such mesangiolysis may indicate previous injury of thrombotic microangiopathy (TMA) as there is no active TMA (methenamine silver stain,original magnification [x]400). (d) Direct immunofluorescence study showing global mesangial and capillary deposit of immunoglobulin G in a finegranular pattern (original magnification [x]400). (e) Electron microscopy. According to the American College of Medical Genetics/Association for Molecular Pathology classification, these two variants are considered pathogenic. A loss-of-function in the DGKE gene is associated with a prothrombotic state, leading to episodes of HUS that are complement-independent.1 Interestingly, a subset of patients develop MPGN with nephrotic syndrome.2 Along with the new classification, it is believed that chronic microangiopathy often results in a form of MPGN that is neither immune complex[-]mediated nor complement-mediated.3 The exact mechanism of DGKE mutations leading to MPGN remains unknown.

BH4 is an essential cofactor for PAH, TH, and TPH We describe a 2-year-old boy who was referred by the Maternity Child Health Clinic to the Department of Paediatrics in June 2014 for assessment of developmental delay. Another mutation affecting the same amino acid p.Leu287Gly has been reported previously in patients with phenylketonuria (PKU).2 In-silico analyses by four prediction software (PolyPhen-2, SIFT, Mutation Taster, PON-P2) also consistently predicted that the mutation is pathogenic. [...]PAH c.860T[greater than]C (p.Leu287Pro) is highly likely to be a pathogenic mutation. PAH gene dosage analysis by multiplex ligation probe amplification (SALSA MLPA probemix P055-C1 PAH) did not detect any PAHgross deletion or duplication. [...]the secondPAH mutation of this patient remained unidentified. Hong Kong cannot afford to have more intellectual disability as a result of the unavailability of PKU screening. [...]this programme becomes universally available, we advocate plasma amino acid and urine organic acid analysis to be incorporated into the diagnostic workup for all children with unexplained developmental delay, intellectual disability, behavioural problems, and autistic spectrum disorders. 1.