Penile length of term newborn infants in multiracial Malaysia.

Introduction: Micropenis may be an important sign of underlying hypogonadism or pituitary hypofunction in the neonatal period. Penile lengths of normal newborns have been reported in many Western populations. However, the data may not be applicable in the Asian or the multiracial Malaysian population. Our study aimed to establish the normal penile length and testicular volume in term newborn infants in the major ethnic groups in Malaysia. Methods: The stretched penile length and testicular volume were measured in 340 normal term newborn infants (195 Malays, 129 Chinese and 16 Indians). Results: The mean penile length in Malay term newborn infants was 35 +/- 4 mm, which was similar to Chinese infants. The mean testicular volume was 2.5 +/- 0.6 ml in Malay and 2.4 +/-0.5 ml in Chinese infants. There was no significant difference between the groups. The sample size for the Indian group during the study period was inadequate. Conclusion: Using -2.5 standard deviations as the cut-off for micropenis, a Malay or Chinese newborn infant in Malaysia with a penile length of less than 25 mm is considered to have a micropenis and further evaluation is warranted

Vitamin-D-deficiency rickets even with abundant sunlight - a case to highlight emerging problem

We describe a case of vitamin-D-deficiency rickets in a young child to highlight its existence in Malaysia where sunlight is abundant throughout the year. The child presented with deformity of both legs. He came from an educated urban family but remained indoors most of the time. Radiographs of knees and wrists showed changes of florid rickets. Low serum 25-hydoxyvitamin-D, high parathyroid hormone, normal serum phosphate and calcium levels, and normal renal function clinched the diagnosis of vitamin-D-deficiency rickets. He improved remarkably after treatment with oral Vitamin-D. We emphasise the importance of exposure to sunlight to prevent rickets

Genetic basis of hereditary hypophosphataemic rickets and phenotype presentation in children and adults

Hypophosphataemic rickets (HR) is a genetic disorder causing defects in the renal handling of phosphorus, resulting in rickets. HR can be classified into two groups. First — those with excess fibroblast growth factor 23 (FGF23) levels, which are due to gene mutations in extrarenal factors and include X-linked dominant hypophosphataemic rickets (XLHR), autosomal dominant hypophosphataemic rickets (ADHR), autosomal recessive hypophosphataemic rickets (ARHR), and hypophosphataemic rickets with hyperparathyroidism. Second — those with normal or low FGF23, which are caused by gene mutations in renal tubular phosphate transporters and include hereditary hypophosphataemic rickets with hypercalciuria (HHRH) and X-linked recessive hypophosphataemic rickets. The radiographical changes and clinical features of rickets in various types of HR are similar but not identical. Short stature, bone deformities mainly in the lower limbs, and dental problems are typical characteristics of HR. Although the initial diagnosis of HR is usually based on physical, radiological, and biochemical features, molecular genetic analysis is important to confirm the diagnosis and differentiate the type of HR. In this review, we describe clinical and biochemical features as well as genetic causes of different types of HR. The clinical and biochemical characteristics presented in this review can help in the diagnosis of different types of HR and, therefore, direct genetic analysis to look for the specific gene mutation

Dietetic practices in the management of childhood obesity in Malaysia

Introduction: Dietitians play an essential role in the management of childhood obesity and consistency in dietetic practices is required to ensure the effectiveness of treatment. This study assessed dietitians' current practices in the management of childhood obesity, compared the practices with nutrition practice guidelines used by dietitians in other countries and identified practice components for the development of nutrition practice guidelines for the management of childhood obesity in Malaysia. Methods: A cross-sectional study was conducted among 40 dietitians in 16 Ministry of Health hospitals and three teaching hospitals. Information on current dietetic practices in the management of childhood obesity was obtained through a mailed survey questionnaire. The practices included nutritional assessment, determination of energy requirement, dietary prescription and physical activity modification. Emails were sent to 31 dietetic associations in other countries to obtain information on practice guidelines used by dietitians. Results: Frequently used dietary intervention and physical activity modification approaches were high fibre diet (65%), low fat diet (40%), reduction of sedentary pursuits and screen times (67.5%) and an increase in duration of current physical activities (60%). In comparison to other dietetic practice guidelines, the current dietetic practices in Malaysia do not usually include waist circumference, biochemical and blood pressure data. However, similar to other guidelines, the current dietetic practices included low dietary fat, high fibre diet, decreased sedentary activity and increased physical activity level. Conclusions: The dietetic practices in the management of childhood obesity in Malaysia are diverse. A comprehensive nutrition practice guideline for management of childhood obesity is urgently needed for standardisation of dietetic practices in Malaysia

Early transition from insulin to sulfonylureas in neonatal diabetes and follow-up: experience from China

Background: Sulfonylurea therapy can improve glycemic control and ameliorate neurodevelopmental outcomes in patients suffering from neonatal diabetes mellitus (NDM) with KCNJ11 or ABCC8 mutations. As genetic testing results are often delayed, it remains controversial whether sulfonylurea treatment should be attempted immediately at diagnosis or doctors should await genetic confirmation. Objective: This study aimed to investigate the effectiveness and safety of sulfonylurea therapy in Chinese NDM patients during infancy before genetic testing results were available. Methods: The medical records of NDM patients with their follow‐up details were reviewed and molecular genetic analysis was performed. Sulfonylurea transfer regimens were applied in patients diagnosed after May 2010, and glycemic status and side effects were evaluated in each patient. Results: There were 23 NDM patients from 22 unrelated families, 10 had KCNJ11 mutations, 3 harbored ABCC8 mutations, 1 had INS mutations, 4 had chromosome 6q24 abnormalities, 1 had a deletion at chromosome 1p36.23p36.12, and 4 had no genetic abnormality identified. Sixteen NDM infants were treated with glyburide at an average age of 49 days (range 14‐120 days) before genetic confirmation. A total of 11 of 16 (69%) were able to successfully switch to glyburide with a more stable glucose profile. The responsive glyburide dose was 0.51 ± 0.16 mg/kg/d (0.3‐0.8 mg/kg/d), while the maintenance dose was 0.30 ± 0.07 mg/kg/d (0.2‐0.4 mg/kg/d). No serious adverse events were reported. Conclusions: Molecular genetic diagnosis is recommended in all patients with NDM. However, if genetic testing results are delayed, sulfonylurea therapy should be considered before such results are received, even in infants with newly diagnosed NDM

Predicting the impact of PHEX, FGF23 and DMP1 gene variants found in Malaysian Malay patients with Hypophosphataemic Rickets through in silico analysis of protein function and mRNA secondary structure

Hypophosphataemic Rickets (HR) is a rare bone disorder characterised by chronic hypophosphataemia caused by defective phosphate reabsorption in the renal tubules. Variants in phosphate-regulating endopeptidase homolog, X-linked (PHEX), fibroblast growth factor-23 (FGF23) and dentin matrix protein-1 (DMP1) genes contribute to X-linked dominant, autosomal dominant and autosomal recessive forms of HR, respectively. In this study, four Malaysian patients’ DNA samples were subjected to polymerase chain reaction and Sanger sequencing to identify the types and locations of the variants. Then, in silico study was conducted based on the variants found to predict the effects of amino acid substitution on protein functions using SIFT and PolyPhen-2 software and RNAfold was used to construct the mRNA secondary structure. Mutational analyses had revealed two variants in PHEX; c.10G>C (E4Q), c.1970A>G (Y657C), one mutation in FGF23; c.716C>T (T239M) and three variants on DMP1; c.309A>T (S69C), c.1322C>T (S406S), c.1334G>A (E410E). The variants in these Malay patients were previously reported in different ethnic HR patients. Protein prediction programs suggested that the PHEX Y657C and DMP1 S69C variants may affect protein function. All variants were predicted to alter the secondary mRNA structure. These findings suggest that these missense and silent variants may lead to changes in protein function and mRNA secondary structure that are associated with the manifestation of HR phenotype

Reversible posterior leukoencephalopathy syndrome in post streptococcal glomerulonephritis

Reversible Posterior Leukoencephalopathy syndrome (RPLS) is a uncommon neurological disorder among pediatric population. Clinical features started with decreased alertness and activity, and associated with headache, visual changes, altered mental status such as seizures, confusion and abnormal behavior. Radio imaging findings commonly present typical changes in the white matter located in the posterior regions of the cerebral hemisphere and cerebellum. This syndrome commonly associated with hypertension, ecclampsia, renal failure or the used of some immunosuppression medications especially cyclosporine and tacrolimus. We describe a previously healthy 9-year-old boy who presented with acute post-streptococcal glomerulonephritis, and he developed neurological symptoms of posterior leukoencephalopathy syndrome with hypertensive crisis. His CT scan shows typical changes of non enhancing white matter with hypodensities at the occipital and parietal temporal areas. He had a rapid resolution of neurological symptoms with adequate treatment of hypertension. He was discharged well after 14 days in the ward

Clinical and mutational features of three Chinese children with congenital generalized lipodystrophy

Objective: To investigate the clinical and molecular features of congenital generalized lipodystrophy (CGL) in three Chinese patients with various typical manifestations. Methods: Data on clinical symptoms, results of laboratory analyses, and previous treatments in three Chinese patients were collected by a retrospective review of medical records. All coding regions and adjacent exon–intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase chain reaction and sequenced.Results: Generalized lipodystrophy, acanthosis nigricans, muscular hypertrophy, severe hypertriglyceridemia, and hepatomegaly were features in all three patients. Patient 1 developed diabetes mellitus at the early age of 2 months and he was the youngest CGL patient reported with overt diabetes. Patient 2 was found to have cardiomyopathy when she was aged 6 months. All of the patients were found to have mutations in the BSCL2 gene, but none of these was a novel mutation. We did not find any AGPAT2 mutation in our patients.Conclusion: All of our patients exhibited characteristic features of CGL due to mutations in the BSCL2 gene

Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets

Hypophosphatemic rickets (HR) is a syndrome of hypophosphatemia and rickets that resembles vitamin D deficiency, which is caused by malfunction of renal tubules in phosphate reabsorption. Phosphate is an essential mineral, which is important for bone and tooth structure. It is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D and fibroblast-growth-factor 23 (FGF23). X-linked hypophosphatemia (XLH), autosomal dominant HR (ADHR), and autosomal recessive HR (ARHR) are examples of hereditary forms of HR, which are mainly caused by mutations in the phosphate regulating endopeptidase homolog, X-linked (PHEX), FGF23, and, dentin matrix protein-1 (DMP1) and ecto-nucleotide pyro phosphatase/phosphodiesterase 1 (ENPP1) genes, respectively. Mutations in these genes are believed to cause elevation of circulating FGF23 protein. Increase in FGF23 disrupts phosphate homeostasis, leading to HR. This review aims to summarize phosphate homeostasis and focuses on the genes and mutations related to XLH, ADHR, and ARHR. A compilation of XLH mutation hotspots based on the PHEX gene database and mutations found in the FGF23, DMP1, and ENPP1 genes are also made available in this review

Nutritional rickets in three toddlers during Covid-19 pandemic lockdown

Nutritional rickets is a worldwide problem which has been increasingly reported globally. Three toddlers aged 1-2 years presented in March to April 2021 with bony deformities following one year of national Covid-19 pandemic lockdown since March 2020. All three patients were breastfed till presentation without formula milk supplementation. Weaning occurred at 4-6 months of age but without proper complementary food intake. All three patients and their nursing mothers were mostly confined indoors during the pandemic lockdown. Bone metabolic profile and radiological imaging confirmed vitamin D deficiency rickets. All three patients responded well to vitamin D3 treatment and calcium supplementation for 3-6 months duration. Vitamin D deficiency rickets appears to be an increasing problem in breastfed toddlers following the prolonged movement control order, particularly amongst picky eaters and young children on restrictive diets. Sun exposure and early vitamin D supplementation are crucial to prevent the development of nutritional rickets