Favourable outcome in a child with symptomatic diagnosis of Glutaric aciduria type 1 despite vertical HIV infection and minor head trauma

Angeline Thomas, Els F. M. Dobbels, Priscilla E. Springer, Christelle Ackermann, Mark F. Cotton, Barbara Laughton

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.