Could nodding syndrome in Northern Uganda be a form of autism spectrum disorder? an observational study design

Abstract

IntroductionNodding syndrome (NS) is associated with high anion gap, biotinidase and acetyl carnitine deficiency, vitamin B6 and D deficiency and internal displacement. The objective of this study was to conduct a metabolic analysis on NS children and review literature on its similarities with ASD.MethodsWe conducted biochemical analysis on blood and urine of NS children at Hope for HumaNs (HfH) centre in 2014 and reviewed literature on its similarities with ASD. Ethical approval was obtained from an IRB. Data analysis was conducted using STATA version 12 and a p-value less than 0.05 was considered significant.ResultsWe found biotinidase deficiency in NS with a mean 1.98 95% CI(1.61, 2.34; p < 0.001); Acetyl carnitine deficiency 16.92 95% CI(16.10,17.75; p<0.001); Low BMI-for-age 16.92 95% CI(16.10,17.75; p = 0.42); Age 14.08 95% CI(0.78,4.660; p = 0.007); IDP duration 4.82 95% CI(4.48, 5.21; p = 0.92); Age at NS onset 8.02 95% CI(7.03, 9.01; p = 0.001); NS associated with multiple nodding episodes (χ2)=22.15, p=0.005; NS siblings with NS (χ2) = 9.68, p = 0.004; NS were in IDPs (χ2) = 22.15, p = 0.005.ConclusionThese findings are indicative that NS is associated with biotinidase and acetyl carnitine deficiency, IDPs, and environmental exposures. There are no new cases of NS reported by Ugandan MOH and WHO since 2012 when the IDP camps were disbanded and communities resettled in their own communities and feed on their own grown foods. Perhaps NS may be akin to Autism Spectrum Disorder (ASD). This finding will help support all efforts towards the treatment and rehabilitation of NS children.

Aetiologies and therapies of nodding syndrome: a systematic review and meta-analysis

“…This led to the hypothesis that the rise in NS cases may have been linked to the consumption of specific foodstuffs regularly supplied in the IDP camps. 15 , 22 , 26 Four case-control studies have provided mixed conclusions regarding the association between consumption of (spoiled) relief foods and NS. 6 , 21 , 27 , 28 Tumwine and colleagues were the first to suggest an association with food, specifically serena, a type of red/brown sorghum.…”

“…36 It has also been suggested that this metabolic acidosis may reflect underlying mitochondrial dysfunction 35 -36 ; however, analysis of three cases did not detect any aberrations in mitochondrial DNA. 37 The serum biotinidase and acetyl carnitine levels of 47 Ugandan NS cases were found to be abnormally low 23 , generating speculation that NS may represent the influence of metabolic disruption upon the central nervous system (CNS) 15 , as has been hypothesised for autism-spectrum disorders. 38 -39 Vitamin D deficiency has also been noted among NS patients, and could reflect more time spent indoors due to stigmatisation, the use of anticonvulsants or an aspect of the condition itself.…”

Nodding Syndrome and Autism Spectrum Disorder

“…The syndrome was first described in 1st scientific meeting organized by the Ugandan Ministry of Health (MOH) and World Health Organization (WHO) in Sheraton, Kampala, Uganda in 2012 [4]. The outcome of the meeting was the agreed WHO epidemiological and surveillance case definition of probable nodding syndrome [5,6]. It states, "Probable NS cases should meet the following criteria:…”

“…In addition, it has been observed that nodding episodes were stimulated by sights of local food, starvation, exposure to cold weather/temperatures, cold water, stress, physical exercises and there was an association with high anion gap and that most NS began in the internally Displaced Peoples camps (IDPs) or immediately after resettlement into the satellite camps and eventually to their original villages [1][2][3][4][5]. Researchers propose that NS is an emerging neurological disorder in Eastern Africa likely due to factors that were experienced during the IDPs [1,[3][4][5] and that no new NS cases have been reported since 2012 by the Ugandan Ministry of Health (MOH) and WHO after the IDP camps were disbanded and the affected communities resettled in their villages [1,3,5].…”

“…Interestingly, all communities where NS occur at epidemic proportion experienced some degree of internal displacement before the onset of NS [2,3,5]. In addition, there is a widely held belief among the affected communities in Northern Uganda that NS had possibly originated from contaminated relief food provided during IDPs or exposure to war munitions/chemicals during the protracted 20 year old war in Northern Uganda between the rebel, Lord's Resistance Army (LRA) and the Government of Uganda where 90% of the population in Acholi were displaced into IDPs [8,9].…”