Abstract
The first case of Glutaric aciduria Type 1(GA1) in an African child was reported in 2001. GA1 has a prevalence of 1:5000 in black South Africans. Although early diagnosis is essential for a favourable outcome, newborn screening is not routine in South Africa where an estimated 320,000 children have HIV infection. Neurodevelopmental delay and encephalopathy are complications of both HIV and GA1. In such a setting it is important to recognise that HIV and GA1 can occur simultaneously. We present an HIV-infected South African male child of Xhosa descent with macrocephaly who commenced combination antiretroviral therapy (ART) at 8 weeks of age in a clinical trial which included a neurodevelopmental sub-study. He developed short-lived focal seizures at 16 months after minor head trauma. Neurological examination was normal. Neuroimaging showed temporal lobe atrophy, subtle hyperintense signal change in the globus pallidus, and focal haemosiderosis in the right Sylvian fissure region. As findings were not in keeping with HIV encephalopathy, a urine metabolic screen was undertaken which suggested GA1. Genetic testing confirmed Arg293Trp mutation. He began L-carnitine and a low protein diet as a restricted diet was not practicable. At 21 months he developed pulmonary tuberculosis, requiring 6 months treatment. He did not develop any neurologic motor symptoms. Serial neurodevelopmental and neuropsychological test scores until 9 years were similar to healthy neighbourhood controls, except for mild language delay at 3½ years. Detection of GA1, probably facilitated through participation in a clinical trial, was pivotal for a favourable outcome. The concomitant use of ART and anti-tuberculous therapy in a child with GA1 appears safe.
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Acknowledgements
We would like to thank the participant and his mother for taking part in the study and the KID-CRU personnel. The authors would like to thank Drs Jennifer Cartwright and George van der Watt for their contributions in managing this patient and advice on the manuscript. Support for the CHER trial was provided by the US National Institute of Allergy and Infectious Diseases through the CIPRA network, Grant U19 AI53217; the Departments of Health of the Western Cape and Gauteng, South Africa; and GlaxoSmithKline. Additional support was provided with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States Department of Health and Human Services, under Contract No. HHSN272200800014C. Neurodevelopmental assessments from 0 to 5 years were funded through grants from the Harry Crossley Foundation and the South African Medical Research Council, the National Research Foundation of South Africa and CIPRA-SA. Support for the CHER Plus follow on study, until 9 years was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Grant: R01HD071664-01 and ViiV Healthcare.
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The above child was enrolled on the neurodevelopmental sub-study of the CHER trial. The sub-study approved by the Stellenbosch University health research ethics committee (reg no N05/05/092 and M11/10/042) and was been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent to participate was obtained in person from the child’s mother in her home language. At 9 the child provided assent.
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Thomas, A., Dobbels, E.F.M., Springer, P.E. et al. Favourable outcome in a child with symptomatic diagnosis of Glutaric aciduria type 1 despite vertical HIV infection and minor head trauma. Metab Brain Dis 33, 537–544 (2018). https://doi.org/10.1007/s11011-018-0196-4
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DOI: https://doi.org/10.1007/s11011-018-0196-4