Purine Nucleoside Phosphorylase Deficient Severe Combined Immunodeficiencies: A Case Report and Systematic Review (1975-2022).

Purine nucleoside phosphorylase deficient severe combined immunodeficiency (PNP SCID) is one of the rare autosomal recessive primary immunodeficiency disease, and the data on epidemiology and outcome are limited. We report the successful management of a child with PNP SCID and present a systematic literature review of published case reports, case series, and cohort studies on PNP SCID listed in PubMed, Web of Science, and Scopus from 1975 until March 2022. Forty-one articles were included from the 2432 articles retrieved and included 100 PNP SCID patients worldwide. Most patients presented with recurrent infections, hypogammaglobulinaemia, autoimmune manifestations, and neurological deficits. There were six reported cases of associated malignancies, mainly lymphomas. Twenty-two patients had undergone allogeneic hematopoietic stem cell transplantation with full donor chimerism seen mainly in those receiving matched sibling donors and/or conditioning chemotherapy before the transplant. This research provides a contemporary, comprehensive overview on clinical manifestations, epidemiology, genotype mutations, and transplant outcome of PNP SCID. These data highlight the importance of screening for PNP SCID in cases presented with recurrent infections, hypogammaglobulinaemia, and neurological deficits.

Comparison between the Transcutaneous and Total Serum Bilirubin Measurement in Malay Neonates with Neonatal Jaundice.

Background: This study aims to investigate the reliability of the Dräger Jaundice Meter JM-105 for the screening of neonatal jaundice in Malay neonates. Methods: A cross-sectional study was conducted in a university hospital involving 130 jaundiced neonates requiring serum bilirubin determination from day 2 to day 7 of life. Results: The mean total serum bilirubin (TSB) was 232 µmol/L, whereas the mean transcutaneous bilirubin (TcB) measured at the forehead and sternum were 222 µmol/L and 223 µmol/L, respectively. Further, TcB underestimates TSB with a mean difference of 10.10 µmol/L at the forehead and 9.27 µmol/L at the sternum. A positive linear relationship was observed between TSB with TcB forehead (r = 0.82) and TcB sternum (r = 0.80). A good discriminations ability was observed for both the TcB forehead (receiver operating characteristics [ROC] curve = 89.8%) and sternum (ROC curve = 89.7%) at a TSB level of 205 µmol/L. The sensitivity ranges from 84.4% to 85.3%, while the specificity ranges from 77.4% to 76.4%. Conclusion: Our study demonstrates a strong linear relationship and good diagnostic accuracy of TcB values compared to TSB values. To conclude, TcB measured at the forehead or sternum is a good alternative as a non-invasive screening tool for non-severe hyperbilirubinemia in Malay neonates.

Short versus long feeding interval for bolus feedings in very preterm infants.

BACKGROUND: There is presently no certainty about the ideal feeding intervals for preterm infants. Shorter feeding intervals of, for example, two hours, have the theoretical advantage of allowing smaller volumes of milk. This may have the potential to reduce the incidence and severity of gastro-oesophageal reflux. Longer feeding intervals have the theoretical advantage of allowing more gastric emptying between two feeds. This potentially provides periods of rest (and thus less hyperaemia) for an immature digestive tract. OBJECTIVES: To determine the safety of shorter feeding intervals (two hours or shorter) versus longer feeding intervals (three hours or more) and to compare the effects in terms of days taken to regain birth weight and to achieve full feeding. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in CENTRAL (2020, Issue 6) and Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions, and CINAHL on 25 June 2020. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing short (e.g. one or two hours) versus long (e.g. three or four hours) feeding intervals in preterm infants of any birth weight, all or most of whom were less than 32 weeks' gestation. Infants could be of any postnatal age at trial entry, but eligible infants should not have received feeds before study entry, with the exception of minimal enteral feeding. We included studies of nasogastric or orogastric bolus feeding, breast milk or formula, in which the feeding interval is the intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were days taken to achieve full enteral feeding and days to regain birth weight. Our other outcomes were duration of hospital stay, episodes of necrotising enterocolitis (NEC) and growth during hospital stay (weight, length and head circumference). MAIN RESULTS: We included four RCTs, involving 417 infants in the review. One study involving 350 infants is awaiting classification. All studies compared two-hourly versus three-hourly feeding interval. The risk of bias of the included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies were included in meta-analysis for the number of days taken to achieve full enteral feeding (351 participants). The mean days to achieve full feeds was between eight and 11 days. There was little or no difference in days taken to achieve full enteral feeding between two-hourly and three-hourly feeding, but this finding was of low certainty (mean difference (MD) ‒0.62, 95% confidence interval (CI) ‒1.60 to 0.36). There was low-certainty evidence that the days taken to regain birth weight may be slightly longer in infants receiving two-hourly feeding than in those receiving three-hourly feeding (MD 1.15, 95% CI 0.11 to 2.20; 3 studies, 350 participants). We are uncertain whether shorter feeding intervals have any effect on any of our secondary outcomes including the duration of hospital stay (MD ‒3.36, 95% CI ‒9.18 to 2.46; 2 studies, 207 participants; very low-certainty evidence) and the risk of NEC (typical risk ratio 1.07, 95% CI 0.54 to 2.11; 4 studies, 417 participants; low-certainty evidence). No study reported growth during hospital stay. AUTHORS' CONCLUSIONS: The low-certainty evidence we found in this review suggests that there may be no clinically important differences between two- and three-hourly feeding intervals. There is insufficient information about potential feeding complications and in particular NEC. No studies have looked at the effect of other feeding intervals and there is no long-term data on neurodevelopment or growth.

Randomised controlled trial: Shoulder-umbilicus length versus body weight measurement for optimal endotracheal tube depth estimation in ventilated infants.

AIM: The optimal placement of the endotracheal tube (ETT) in ventilated infants is essential, but birthweight may be not the best parameter to predict it. The aim of this study was a direct comparison of shoulder-umbilical length (experimental group) versus birthweight (control group) as predictor of optimal ETT placement in Malaysian ventilated infants. METHODS: All infants requiring ventilation in the neonatal intensive care unit of a tertiary hospital in Malaysia during the 4-month study period were eligible to enter this randomised controlled trial. All participants were randomised into two groups: experimental and control group. The main outcome measure was malposition of the ETT (requiring adjustment), as seen on the chest X-ray performed within 1 h after intubation. Tube placement was assessed by two neonatologists, blinded to the allocation. RESULTS: One hundred and ten infants were randomised, 55 in each group. The ETT was malpositioned in 13 of 55 infants (23%) for the experimental group and 22 of 55 infants (40%) in the control group (P = 0.06). CONCLUSION: In the experimental group, fewer infants showed a need for tube adjustment than in the control group. While a larger study may be necessary to show statistical significance, the difference shown in this study may be large enough to be of clinical significance.

Developmental haemostasis for factor V and factor VIII levels in neonates: a case report of spontaneous cephalhaematoma.

Combined factor V and VIII deficiency is a rare bleeding disorder. Diagnosis of congenital coagulation factor deficiency in a neonate is challenging due to "immaturity" of the hemostatic system. A 2-day-old baby girl presented with spontaneous cephalhematoma. She was found to have persistent abnormal coagulation tests and finally diagnosed as combined factor V and VIII deficiency. Interestingly, factor V and factor VIII in developmental hemostasis are quite similar with adult levels in newborn, and hence early diagnosis is possible. An investigation to detect underlying hemostatic defects is recommended in newborns with spontaneous cephalhematoma.

Depressive, Anxiety, and Stress Symptoms in Parents of Children Being Admitted for Febrile Seizures in a Tertiary Hospital in the East Coast of Malaysia.

Febrile seizures in children are an alarming experience for parents. This study aimed to assess the psychological functioning of parents of children when they were being admitted for treatment of febrile seizures in the hospital, the importance of which is clear, since parents are the primary custodian of their children. This is a cross-sectional study conducted on 110 participants whose child had been admitted for a febrile seizure to Hospital Universiti Sains Malaysia from September 2020 until June 2021. The depression, anxiety, and stress levels were determined based on a validated Bahasa Melayu questionnaire of the Depression Anxiety Stress Scale (DASS-21). In addition, multiple logistic regression was used to determine the associated factors related to the participants' psychological functioning. The mean age of children with febrile seizures were 21 months old, and most children showed features of simple febrile seizures (71.8%). The prevalence of anxiety, stress, and depression were 58.2%, 29%, and 23.6%, respectively. Using multiple logistic regression, child age, family history of febrile seizures, family history of epilepsy, and length of stay in the ward were found to be significantly associated with anxiety when adjusted for other variables. Otherwise, for depression and stress, no significant associated variables were found when adjusted for other variables. Anxiety was highly reported by participants when their children were admitted for febrile seizures. Several factors impacted their anxiety, including the lower the child's age was, participants with no family history of febrile seizures before, and the longer duration of hospital stay. Therefore, further study and intervention on reducing the parent's anxiety could be emphasized in the future.

Craniofacial deformities in transfusion-dependent thalassemia patients in Malaysia: prevalence and effect of treatment.

This comparative cross-sectional study was conducted in the pediatric daycare unit, Hospital Universiti Sains Malaysia to determine the prevalence of craniofacial deformities (CFD) and the association between these deformities and different clinical presentations among thalassemia patients. Patients were classified as either craniofacial deformity positive (CFD+) or craniofacial deformity negative (CFD-) by two examiners based on the presence or absence of deformity of the cheeks, frontal and/or maxillary bones. Fifteen clinical parameters were compared between the groups. Nineteen out of 43 patients (44.2%; confidence interval, 30.2-58.2%) had craniofacial deformities (CFD+). Both groups were comparable among the clinical parameters studied. Patients in the CFD+ group did not start their blood transfusions significantly earlier than the CFD- group (p = 0.50) and had a nonsignificantly lower mean pretransfusion hemoglobin level than the CFD- group (p = 0.71). Patients receiving regular monthly blood transfusions had a nonsignificantly smaller percentage of CFD than those transfused less often (p = 0.495). CFD+ patients had a splenectomy at a nonsignificantly younger age than CFD- patients (p = 0.36). HbE/beta thalassemia patients were not significantly less likely to develop CFD than other varieties (p = 0.50) and males had a nonsignificantly higher percentage of CFD than females (p = 0.29). This study shows CFD in thalassemia patients are still prevalent but no significant associated factors were found; however, a nonsignificantly higher prevalence of CFD was observed in patients with signs of severe disease and less efficient treatment.

Skeletal, dentoalveolar, and soft tissue cephalometric measurements of Malay transfusion-dependent thalassaemia patients.

Thalassaemia is a public health problem in Malaysia. It is known to cause skeletal deformity. The purpose of this study was to compare the skeletal, dentoalveolar, and soft tissue features of Malay transfusion-dependent thalassaemia (TDT) patients with a Malay control group. Lateral cephalometric radiographs of 30 Malay (14 males and 16 females aged 6.4-21.8 years) TDT patients and 60 normal Malays matched for chronological age and gender were analysed and compared using an independent t-test. The TDT group showed a similar sagittal relationship to the control group but with a significantly increased (P < 0.01) mandibular plane inclination. They also showed a significantly shorter (P ≤ 0.001) mandibular body, ramus length, and posterior face height and consequently a smaller ratio of posterior to anterior face height (P < 0.01). The upper and lower lips were significantly procumbent (P < 0.001) in the TDT group together with a significantly smaller nasolabial angle (P < 0.05). Dentoalveolar measurements showed less proclined maxillary teeth in the TDT group compared with the controls (P < 0.05). The cephalometric features of Malay TDT patients were characterized by a mild Class II skeletal pattern, prominent vertical growth direction of the mandible, and protruded upper and lower lips.

A Randomized Controlled Trial Comparing Two Doses of Caffeine for Apnoea in Prematurity.

Caffeine is the most commonly used methyl xanthine for the prevention of apnoea in prematurity, but the ideal dose was uncertain, until now. This study compared two doses of caffeine for the prevention of apnoea in prematurity. A clinical trial was conducted on 78 preterm infants ≤32 weeks in Neonatal Intensive Care Unit. They were randomly allocated to receive the intervention (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) or the control (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) dose of caffeine. The primary outcome of the study was the frequency and total days of apnoea per duration of treatment for both groups. The frequency of apnoea ranged from zero to fourteen in the intervention group and zero to twelve in the control group. There was no statistically significant difference between the groups, with a p-value of 0.839. The number of days of apnoea was also similar between both groups, with a p-value of 0.928. There was also no significant difference in adverse events between both regimens. This study did not support the use of higher doses of caffeine as a prevention for apnoea in prematurity.

Timing and predictive factors of developing chronic kidney disease in childhood-onset idiopathic nephrotic syndrome: an Asian experience.

INTRODUCTION: Idiopathic nephrotic syndrome (INS) is the commonest type of nephrotic syndrome in children, and a majority of cases have favourable outcomes. A small proportion of INS cases progress to chronic kidney disease (CKD). We investigated the time to CKD and predictive risk factors associated with progression of CKD in these children. METHODS: A retrospective review of medical records was done to investigate the demographic variables, and biochemical and histological changes in children with INS aged 12 months to 18 years between 2001 and 2016 at Hospital Universiti Sains Malaysia. The median renal survival time for progression to CKD stage III or higher was determined using survival curve analysis. Multiple Cox regression analysis was used to identify predictive factors for CKD. RESULTS: The total number of participants was 112 (boys: n = 71; girls: n = 41) and a majority had steroid-sensitive INS. Only about 10% of INS progressed to CKD Stage III or higher, with an overall median renal survival time of 19 years. Median renal survival time in steroid-resistant nephrotic syndrome (SRNS) was 13 years. Focal segmental glomerulosclerosis was predominant in SRNS. The predictors of progression to CKD were steroid resistance (adjusted hazard ratio [HR] [95% confidence interval (CI)] 23.8 [2.8-200.9]) and the presence of hypertension at presentation (adjusted HR [95% CI] 8.1 [1.2-55.7]). CONCLUSION: The median renal survival time in our study was comparable to other studies. SRNS and the presence of hypertension at presentation were the main predictors for developing CKD in our population.

Two-hourly versus 3-hourly feeding for very low birthweight infants: a randomised controlled trial.

OBJECTIVE: To determine whether feeding with 2-hourly or 3-hourly feeding interval reduces the time to achieve full enteral feeding and to compare their outcome in very low birthweight preterm infants. DESIGN: Parallel-group randomised controlled trial with a 1:1 allocation ratio. SETTING: Two regional tertiary neonatal intensive care units. PATIENTS: 150 preterm infants less than 35 weeks gestation with birth weight between 1.0 and 1.5 kg were recruited. INTERVENTIONS: Infants were enrolled to either 2-hourly or 3-hourly interval feeding after randomisation. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was time to achieve full enteral feeding (≥100 mL/kg/day). Secondary outcomes include time to regain birth weight, episode of feeding intolerance, peak serum bilirubin levels, duration of phototherapy, episode of necrotising enterocolitis, nosocomial sepsis and gastro-oesophageal reflux. RESULTS: 72 infants were available for primary outcome analysis in each group as three were excluded due to death-three deaths in each group. The mean time to full enteral feeding was 11.3 days in the 3-hourly group and 10.2 days in the 2-hourly group (mean difference 1.1 days; 95% CI -0.4 to 2.5; p=0.14). The mean time to regain birth weight was shorter in 3-hourly group (12.9 vs 14.8 days, p=0.04). Other subgroup analyses did not reveal additional significant results. No difference in adverse events was found between the groups. CONCLUSION: 3-hourly feeding was comparable with 2-hourly feeding to achieve full enteral feeding without any evidence of increased adverse events. TRIAL REGISTRATION NUMBER: ACTRN12611000676910, pre-result.

Prevalence of asthma-like symptoms and assessment of lung function in schoolchildren born with low birth weight.

INTRODUCTION: This study aimed to determine the prevalence of asthma-like symptoms among schoolchildren with low birth weight (LBW), and to compare the lung function of these children with that of children with normal birth weight. METHODS: This was a comparative cross-sectional study. We recruited children aged 8-11 years from eight primary schools in Kota Bharu, Kelantan, Malaysia. The children were divided into two groups: those with LBW (< 2,500 g) and those with normal birth weight (≥ 2,500 g). Parents of the enrolled children were asked to complete a translated version of the International Study of Asthma and Allergies in Childhood questionnaire. Lung function tests, done using a MicroLoop Spirometer, were performed for the children in both groups by a single investigator who was blinded to the children's birth weight. RESULTS: The prevalence of 'ever wheezed' among the children with LBW was 12.9%. This value was significantly higher than that of the children with normal birth weight (7.8%). Forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow when 50% and 75% of the FVC had been exhaled were significantly lower among the children with LBW as compared to the children with normal birth weight. CONCLUSION: LBW is associated with an increased prevalence of asthma-like symptoms and impaired lung function indices later in life. Children born with LBW may need additional follow-up so that future respiratory problems can be detected early.

Multiplex amplification refractory mutation system (MARMS) for the detection of ß-globin gene mutations among the transfusion-dependent ß-thalassemia Malay patients in Kelantan, Northeast of Peninsular Malaysia.

The aim of this study was to adapt MARMS with some modifications to detect beta mutation in our cohort of thalassemia patients. We focused only on transfusion-dependent thalassemia Malay patients, the predominant ethnic group (95%) in the Kelantanese population. Eight mutations were identified in 46 out of 48 (95.83%) beta thalassemia alleles. Most of the patients (54.2%) were compound heterozygous with co-inheritance Cd 26 (G>A). The frequencies of spectrum beta chain mutation among these patients are presented in Table 2. Among the transfusion dependent beta thalassemia Malay patients studied, 26 patients were found to be compound heterozygous and the main alleles were Cd 26 (G>A). Compound heterozygous mutation of Cd 26 (G>A) and IVS 1-5 (G>C) were 12 (46.2%), Cd 26 (G>A) and Cd 41/42 (TTCT) were 9 (34.6%), Cd 26 (G>A) and IVS 1-1 (G>C) were 2 (7.7%) respectively. Meanwhile the minority were made of a single compound heterozygous of Cd 26 (G>A) and Cd 71/72, Cd 26 (>A) and Cd 17 (A>T), Cd 26 (G>A) and -28 (G>A) respectively. Twenty out of forty six patients were shown to have homozygous of IVS 1-5 (G>C) were 2 (10.0%), Cd 26 (G>A) were 15 (75.0%), Cd 19 (A>G) were 1 (5.0%), and IVS 1-1 (G>T) were 2 (10.0%). The beta chain mutations among the Kelantanese Malays followed closely the distribution of beta chain mutations among the Thais and the Malays of the Southern Thailand. The G-C transition at position 5 of the IVS 1-5 mutation was predominant among the Malay patients. In conclusion, this method has successfully identified the mutation spectrum in our cohort of transfusion-dependent beta thalassemia patients, and this method is equally effective in screening for mutation among thalassemia patients.

Infantile fibrosarcoma of the penis in a 2-year-old boy.

Fibrosarcoma is rare in the pediatric age group. It generally involves the extremities and the trunk but rarely involves the genital area. We report a case of a large fungating infantile fibrosarcoma of the penis in a 2-year-old Malay boy. Partial recovery of the penile structure was achieved after chemotherapy. The difficulty in managing the social and surgical aspect of this case is discussed in our report. To the best of our knowledge, this is the first case report of infantile fibrosarcoma involving the penis in an Asian region.