44 research outputs found
Mucopolysaccharidoses
A group of 7 progressive, multi-system disorders with at least 11 different lysosomal enzyme deficiencies.http://www.specialistforum.co.zaam2016Paediatrics and Child Healt
Medullary neuroschistosomiasis in a pediatric patient : a case report
A pediatric patient with neurological deficit was examined using magnetic resonance imaging (MRI]. The images revealed abnormal signal intensity and enhancement of the spinal cord, indicating myelopathy. Identifying the cause of the myelopathy required a differential diagnosis. Images from MRI included a pre-contrast T1 weighted sagittal sequence, which revealed expansion of the distal lumbar spinal cord and conus medullaris from T10-L1. The T2 weighted sagittal sequence revealed patchy areas of hyperintense signal. We did not notice any chronic hemorrhagic products or cysts. Within the field of view, we saw multifocal areas of bladder wall thickening. Sagittal and axial T1 weighted post gadolinium images demonstrated mixed linear and nodular patchy enhancement of the conus medullaris predominantly anteriorly and along the anterior surface of the meninges. On the 18 day of hospitalization, a spinal biopsy revealed the presence of granuloma with non-viable bilharzia ova, and schistosomiasis of the spinal cord was diagnosed. Although uncommon, when it does occur, schistosomiasis has significant implications. Using MRI, the medical team noticed abnormal features that called for a biopsy, and were thus able to differentiate between medullary schistosomiasis and other infective/inflammatory conditions. A prompt diagnosis is vital for initiating early treatment, and avoiding complications and invasive surgery.http://www.elsevier.com/locate/radcrdm2022Radiolog
Cerebral palsy and criteria implicating intrapartum hypoxia in neonatal encephalopathy – an obstetric perspective for the South African setting
The science surrounding cerebral palsy (CP) indicates that it is a complex medical condition with multiple contributing variables and
factors, and causal pathways are often extremely difficult to delineate. The pathophysiological processes are often juxtaposed on antenatal
factors, genetics, toxins, fetal priming, failure of neuroscientific autoregulatory mechanisms, abnormal biochemistry and abnormal
metabolic pathways. Placing this primed compromised compensated brain through the stresses of an intrapartum process could be the
final straw in the pathway to brain injury and later CP. It is therefore simplistic to base causation of CP on only an intrapartum perspective
with radiological ‘confirmation’, as is often the practice in medico-legal cases in South African courts. The present modalities (magnetic
resonance imaging (MRI) and cardiotocography (CTG)), when available, that retrospectively attempt to determine causation in courts are
inadequate when used in isolation. Unless a holistic scientific review of the case including all contributing clinical factors (antepartum,
intrapartum and neonatal), fetal heart rate monitoring, neonatal MRI if possible (and preferred) or late MRI, and histology (placental
histology if performed) is taken into account, success for the plaintiff or defendant currently in a court of law will depend on eloquent legal
argument rather than true scientific causality. The 10 criteria set out in this article to implicate intrapartum hypoxia in hypoxic-ischaemic
encephalopathy/neonatal encephalopathy serve as a guideline in the medico-legal setting.http://www.samj.org.zadm2022Obstetrics and Gynaecolog
Cerebral palsy and its medicolegal implications in low-resource settings – the need to establish causality and revise criteria to implicate intrapartum hypoxia : a narrative review
The objective of this study was to establish scientific causality and to devise criteria to implicate intrapartum hypoxia in cerebral palsy (CP)
in low-resource settings, where there is potential for an increase in damaging medicolegal claims against obstetric caregivers, as is currently
the situation in South Africa. For the purposes of this narrative review, an extensive literature search was performed, including any research
articles, randomised controlled trials, observational studies, case reports or expert or consensus statements pertaining to CP in low-resource
settings, medicolegal implications, causality, and criteria implicating intrapartum hypoxia. In terms of causation, there are differences
between high-income countries (HICs) and low-resource settings. While intrapartum hypoxia accounts for 10 - 14% of CP in HICs, the
figure is higher in low-resource settings (20 - 46%), indicating a need for improved intrapartum care. Criteria implicating intrapartum
hypoxia presented for HICs may not apply to low-resource settings, as cord blood pH testing, neonatal brain magnetic resonance imaging
(MRI) and placental histology are frequently not available, compounded by incomplete clinical notes and missing cardiotocography
tracings. Revised criteria in an algorithm for low-resource settings to implicate intrapartum hypoxia in neonatal encephalopathy (NE)/
CP are presented. The algorithm relies first on specialist neurological assessment of the child, determination of the occurrence of neonatal
encephalopathy (by documented or verbal accounts) and findings on childhood MRI, and second on evidence of antepartum and
intrapartum contributors to the apparent hypoxia-related CP. The review explores differences between low-resource settings and HICs in
trying to establish causation in NE/CP and presents a revised scientific approach to causality in the context of low-resource settings for
reaching appropriate legal judgments.https://samajournals.co.za/index.php/samj/indexam2024Obstetrics and GynaecologyPaediatrics and Child HealthSDG-03:Good heatlh and well-bein
Causation of term perinatal hypoxic-ischaemic basal ganglia and thalamus injury in the context of cerebral palsy litigation : position statement
Basal ganglia and thalamus (BGT) hypoxic-ischaemic brain injury is currently the most contentious issue in cerebral palsy (CP) litigation
in South Africa (SA), and merits a consensus response based on the current available international literature. BGT pattern injury is strongly
associated with a preceding perinatal sentinel event (PSE), which has a sudden onset and is typically unforeseen and unpreventable.
Antepartum pathologies may result in fetal priming, leading to vulnerability to BGT injury by relatively mild hypoxic insults. BGT injury
may uncommonly follow a gradual-onset fetal heart rate deterioration pattern, of duration ≥1 hour. To prevent BGT injury in a clinical
setting, the interval from onset of PSE to delivery must be short, as little as 10 - 20 minutes. This is difficult to achieve in any circumstances
in SA. Each case needs holistic, multidisciplinary, unbiased review of all available antepartum, intrapartum and postpartum and childhood
information, aiming at fair resolution without waste of time and resources.http://www.samj.org.zaam2024Obstetrics and GynaecologySDG-03:Good heatlh and well-bein
Untargeted urine metabolomics reveals a biosignature for muscle respiratory chain deficiencies
Mitochondrial diseases are a heterogeneous
group of disorders characterised by impaired mitochondrial
oxidative phosphorylation system. Most often for mitochondrial
disease, where no metabolic diagnostic biomarkers
exist, a deficiency is diagnosed after analysing the
respiratory chain enzymes (complexes I-IV) in affected
tissues or by identifying one of an ever expanding number
of DNA mutations. This presents a great challenge to
identify cases to undergo the invasive diagnostic procedures
required. An untargeted liquid chromatography mass
spectrometry metabolomics approach was used to search
for a metabolic biosignature that can distinguish respiratory
chain deficient (RCD) patients from clinical controls (CC).
A cohort of 37 ethnically diverse cases was used. Sample
preparation, liquid chromatography time-of-flight mass
spectrometry methods and data processing methods were
standardised. Furthermore the developed methodology
used reverse phase chromatography in conjunction with
positive electrospray ionisation and hydrophilic interaction
chromatography with negative electrospray ionisation.
Urine samples of 37 patients representing two different experimental groups were analysed. The two experimental
groups comprised of patients with confirmed RCDs and
CC. After a variety of data mining steps and statistical
analyses a list of 12 features were compiled with the ability
to distinguish between patients with RCDs and CC.
Although the features of the biosignature needs to be
identified and the biosignature validated, this study demonstrates
the value of untargeted metabolomics to identify
a metabolic biosignature to possibly be applied in the
selection criteria for RCDs.North-West University, Potchefstroom Campushttp://link.springer.com/journal/113062016-02-28hb201
A case for genomic medicine in South African paediatric patients with neuromuscular disease
DATA AVAILABILITY STATEMENT : The original contributions presented in the study are
included in the article/Supplementary Material, further
inquiries can be directed to the corresponding author/s.Paediatric neuromuscular diseases are under-recognised and under-diagnosed
in Africa, especially those of genetic origin. This may be attributable to various
factors, inclusive of socioeconomic barriers, high burden of communicable
and non-communicable diseases, resource constraints, lack of expertise in
specialised fields and paucity of genetic testing facilities and biobanks in the
African population, making access to and interpretation of results more
challenging. As new treatments become available that are effective for specific
sub-phenotypes, it is even more important to confirm a genetic diagnosis for
affected children to be eligible for drug trials and potential treatments. This
perspective article aims to create awareness of the major neuromuscular
diseases clinically diagnosed in the South African paediatric populations, as
well as the current challenges and possible solutions. With this in mind, we
introduce a multi-centred research platform (ICGNMD), which aims to address
the limited knowledge on NMD aetiology and to improve genetic diagnostic
capacities in South African and other African populations.The National Health Laboratory Services (NHLS) of South Africa; the South African Medical Research Council (SAMRC), The genetics of Neuromuscular Diseases in South African patient populations: the ICGNMD study as well as the National Research Foundation (NRF) of South Africa.https://www.frontiersin.org/journals/pediatricsam2023Paediatrics and Child Healt
Metabolomics of urinary organic acids in respiratory chain deficiencies in children
Metabolomic analysis of the urinary organic acids from 39 selected children with defined respiratory chain
deficiencies (RCDs) was performed using untargeted gas chromatography–mass spectrometry, revealing the
presence of 255 endogenous and 46 exogenous substances. Variable reduction identified 92 variables from the
endogenous substances, which could be analysed by univariate and multivariate statistical methods. Using
these methods, no characteristic organic acid biomarker profile could be defined of practical value for diagnostic
purposes for complex I (CI), complex III (CIII) and multiple complex (CM) deficiencies. The statistical procedures
used did, however, disclose 24 metabolites that were practical highly (d > 0.75) and statistically (p < 0.05)
significant for the combined and clinically closely related group of RCDs. Several of these metabolites occur in
single enzyme inherited metabolic diseases, but most were not previously reported to be linked to the metabolic
perturbations that are due to RCDs. Ultimately, we constructed a global metabolic profile of carbohydrate, amino
acid and fatty acid catabolism, illuminating the diverse and complex biochemical consequences of these
disorders. This metabolomics investigation disclosed a metabolite profile that has the potential to define an extended and characteristic biosignature for RCDs and the development of a non-invasive screening procedure
for these disorders.This study formed part of BioPAD Project BPP007.The South African Department of Science and Technology and North-West University.http://link.springer.com/journal/11306hb2017Paediatrics and Child Healt
Characterization of mtDNA variation in a cohort of South African paediatric patients with mitochondrial disease
Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81 ± 26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients.http://www.nature.com/ejhg/index.htm