A review of patients with glutaric aciduria type 1 at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.

Glutaric aciduria type 1 (GA1) is an organic acidaemia. The objective of this study was to describe the profile of patients diagnosed with GA1 at Inkosi Albert Luthuli Central Hospital, Durban, South Africa from 2007 to 2015. We identified 6 children (4 girls, 2 boys) in a retrospective review. The mean age at diagnosis was 12 months. Clinical findings on presentation were encephalopathic crises (n=4), hypotonia (n=4) and macrocephaly (n=5). Other complications included seizures (n=4), dystonia (n=3) and bulbar dysfunction (n=4). Urine organic acid screens showed elevated glutaric acid levels (n=6). Five patients tested positive for the A293T mutation on the glutarylco-enzyme A (CoA) dehydrogenase gene. Abnormalities on magnetic resonance imaging screening included hyperintense basal ganglia (n=6), widened perisylvian fissures (n=6), and an abnormal signal in the cerebral peduncles (n=5) and central tegmental tract (n=4). All patients were treated with L-carnitine and dietary modification. Two patients had a static clinical course, 1 patient gained milestones, and 3 have shown further neuroregression.

The clinical profile and outcome of children with West syndrome in KwaZulu-Natal Province, South Africa: A 10-year retrospective review

Background. West syndrome (WS) is a rare epileptic encephalopathy of infancy. There is currently no research on the incidence or prevalence of WS in Africa.Methods. We aimed to describe the outcome of children with WS at a quaternary-level hospital in KwaZulu-Natal, South Africa (SA). This was a retrospective chart review conducted on patients diagnosed with WS over a 10-year period. Eight children (males, n=7; African, n=6; Asian, n=2) identified with WS out of 2 206 admitted with epilepsy. The median age (range) at diagnosis was 7.5 (1 - 9) months. The average time between onset of epileptic spasms and diagnosis was 3.1 months.Results. Six patients had abnormal neuroimaging (atrophy (n=2); corpus callosum agenesis (n=2); tuberous sclerosis (n=1); focal dysplasia (n=1)). Drug management included sodium valproate (n=8), topiramate (n=7) and levetiracetam (n=3). Subsequent definitive treatment was intramuscular adrenocorticotrophic hormone (n=3), vigabatrin (n=2) and oral prednisone (n=4). Four (50%) patients had complete seizure remission (neuromigratory disorder (n=2); tuberous sclerosis (n=1); and idiopathic (n=1)) and 4 had partial remission (neonatal complications (n=3); idiopathic (n=1).Discussion. Most of our patients had symptomatic WS, with 50% remission on treatment. Outcomes were poorer in our study when compared with those in published data.Conclusion. Further collaborative studies are still needed to evaluate the true impact and prevalence of WS in SA

Diagnosis and management of Pompe disease.

Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease that, if not diagnosed and treated early, can be fatal. It can present from early infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is progressive intracellular accumulation of glycogen. The severity of the disease is determined by age of onset, organ involvement including the degree of severity of muscle involvement, as well as rate of progression. PD is classified into two groups: infantile and late-onset, each having two subgroups. The need for two tests performed by separate methods (screening and confirmatory) is outlined. It is imperative to try to reduce the time to diagnosis and to recognise the possibilities of false-positive results. A multidisciplinary team approach to treatment of affected patients is optimum with, as team leader, a physician who has experience in managing this rare disorder. In this article, we present a brief overview of the disease and provide guidelines for diagnosis and management of this condition in South Africa.

Molecular deletion patterns in Duchenne and Becker muscular dystrophy patients from KwaZulu Natal.

There exists much phenotypic heterogeneity in Duchenne muscular dystrophy and its allelic variant, Becker muscular dystrophy. The molecular findings on 53 patients with Duchenne and 15 patients with Becker type muscular dystrophy in KwaZulu Natal, South Africa are reported. Multiplex PCR was performed using primers targeting 18 hot-spot exons throughout the dystrophin gene. Analysis of the multiplex PCR data revealed that 39/68 (57.0%) patients included in the study showed a deletion (33 DMD and 6 BMD patients). Twenty-five patients were Black, 4 were White and 10 were Indian. Using the Chamberlain and Beggs multiplex PCR assays, the region of the genome most frequently affected by a deletion includes exons 47-51. The distal region of the dystrophin gene was most frequently affected by the deletion in both Black and Indian patients. There were too few White patients for conclusions to be drawn concerning the most frequently affected part of the gene. Although the numbers are insufficient to determine whether ethnic differences are present, the Chamberlain and Beggs multiplex PCR assays detect deletions with the same frequency in South African DMD/BMD patients as that reported in the literature.

Severe Klebsiella infection as a cause of mortality in neonates in Harare, Zimbabwe: evidence from postmortem blood cultures.

Postmortem blood cultures were taken from 105 neonates dying at Harare Hospital during a 1-year period. The infants were characterized by prematurity (63% < 37 weeks gestation), low birth weight (60% < 2500 g) and low Apgar score at 1 min (43% < 3). More than one-half of the infants died within 48 hours of admission. Positive blood cultures within 10 minutes of death occurred in 44% of infants, and Klebsiella sp. were by far the most common isolates. Positive blood cultures were associated with very low birth weight (< 1500 g), and with babies who survived for > 48 hours. Antibodies to human immunodeficiency virus type 1 were found in 40% of the infants, and a high proportion of these had Klebsiella bacteremia. Nearly all the infants had received antibiotic therapy, usually penicillin and gentamicin. Very few babies who had received a cephalosporin had a positive blood culture, and in vitro tests showed that although many organisms were resistant to penicillin and the aminoglycosides, very few showed resistance to the cephalosporins. Our findings suggest that cephalosporins may be useful in treating severe neonatal sepsis, particularly when there is no response to more standard therapy.