Normal Outcome With Prenatal Intervention for Riboflavin Transporter Defect.

BACKGROUND: Riboflavin transporter deficiency is a rare but severe neurometabolic disorder. METHODS: We report two siblings with pathogenic variants in SLC52A3 gene, resulting in riboflavin transporter 3 deficiency. RESULTS: The first sibling was diagnosed at age 11 months with severe respiratory compromise and regression of developmental milestones. His symptoms significantly improved with riboflavin supplementation therapy. The younger sibling was diagnosed by antenatal genetic analysis; riboflavin supplementation was initiated in utero and continued from birth. Now at age two years, he remains clinically asymptomatic despite genetic confirmation of riboflavin transporter deficiency. CONCLUSIONS: Antenatal riboflavin supplementation is a safe and effective treatment for the prevention of symptomatic manifestations of riboflavin transporter deficiency.

Epileptic spasms: A South African overview of aetiologies, interventions, and outcomes.

AIM: To better understand the aetiologies of epileptic spasms in infants, as well as the safety and efficacy of high dose corticosteroids in tuberculosis and human immunodeficiency virus (HIV) endemic resource-limited settings. METHOD: This was a retrospective analysis of infants with epileptic spasms managed at the tertiary referral centres in the Western Cape, South Africa. RESULTS: Of 175 children with epileptic spasms, the median age at onset was 6 months (interquartile range 4-8 months). Structural aetiologies were most common (115 out of 175 [66%]), with two-thirds related to perinatal insults. A lead time to treatment (LTTT) of less than 1 month was more likely in the epileptic encephalopathy/developmental and epileptic encephalopathy (DEE) group: 58 out of 92 (63%), compared to 28 out of 76 (37%) of those with developmental encephalopathy (p = 0.001). Failure to recognize preceding developmental delay was common. Ninety-nine children (57%) received first line hormonal therapy such as adrenocorticotropic hormone. A total of 111 out of 172 children (65%) from the developmental encephalopathy and epileptic encephalopathy/DEE groups had clinical and/or electroencephalogram resolution of spasms within 14 days. In our population, children in whom an aetiology could not be identified were statistically more likely to have moderate to profound developmental delay at 1 year of age: 33 out of 44 (p = 0.001). Based on reported incidence of epileptic spasms, 23 to 58 cases per annum would be expected but a far smaller proportion presented to our centres. INTERPRETATION: Whilst this is the largest cohort of infants with epileptic spasms from sub-Saharan Africa, the study size is less than expected; this may reflect misdiagnosis and failure of referral pathways. Despite a reported shorter LTTT, infants with DEE had worse developmental outcomes compared to international studies. Hormonal therapy was safe and effective in our setting, despite exposure to high levels of tuberculosis and HIV. WHAT THIS PAPER ADDS: The number of unreferred cases of epileptic spasms in South Africa remains high. Caregivers and health care workers in primary care facilities often fail to recognize developmental delay. The burden of disease from hypoxic-ischaemic encephalopathy remains high in our resource-limited setting. Hormonal treatment (e.g. adrenocorticotropic hormone) was safe and effective despite the high prevalence of human immunodeficiency virus and tuberculosis.

A case for genomic medicine in South African paediatric patients with neuromuscular disease.

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.

Epileptic spasms: Evidence for oral corticosteroids and implications for low and middle income countries.

Implementation of international guidelines for the treatment of epileptic spasms, is challenging when access to adrenocorticotrophic hormone (ACTH) and vigabatrin is restricted, especially in Low and Middle Income Countries (LMIC). Oral corticosteroids are alternative interventions but evidence for the optimal agent, dose, duration, efficacy and long-term effects is lacking. A systematic review of the literature was performed to assess the quality of evidence of prednisone and prednisolone (oral corticosteroids) for the management of epileptic spasms. There is level C recommendation based on class III evidence to support the efficacy of oral corticosteroids for the acute clinical control of epileptic spasms and EEG resolution. Efficacy of oral corticosteroids in comparison to the internationally recommended intervention of ACTH has class IV evidence supporting level U recommendation. Similarly, there is no data on the risk of relapse with oral corticosteroids (class IV, level U), compared to ACTH. There is class IV evidence supporting level U recommendation for the safety of oral corticosteroids and class II evidence for level B recommendation for ACTH. In terms of oral corticosteroids and effects on long-term development there is class IV evidence leading to level U recommendation, compared to class III evidence supporting level C recommendation for ACTH. Randomized controlled studies are needed to compare oral corticosteroids with ACTH, the optimal dosage and regimen as well as the long-term neurodevelopmental outcomes. Based on the limited existing studies a treatment guideline for LMIC is proposed which could be used to standardize interventions permitting clarification of these unmet questions.