P74 – 2429: A review of a series of patients with type 1 glutaric aciduria at Inkosi Albert Luthuli Central Hospital, Durban, South Africa

Abstract

Objective To describe the clinical profile, diagnosis and treatment of patients with Type 1 Glutaric Aciduria. Methods A retrospective review of children with a confirmed diagnosis at Inkosi Albert Luthuli Hospital, South Africa. Results We identified 5 children (3 females, 2 Males) during the period 2007–2014. The mean age at diagnosis was 11 months (range 7–22 months). Three patients presented in acute encephalopathic crises. Two patients had an insidious presentation-developmental delay (n=1) and hemiparesis (n=1). The clinical findings on presentation were hyptonia (n=4), hemiparesis (n=1) and macrocephaly (n=5). Two children had a history of pre-morbid developmental delay. Four children had neuro-regression on presentation. Other complications included seizures (n=3), dystonia (n=2). Urine organic acid screens showed elevated glutaric acid in all patients. Of the 4 patients tested, all were positive for the common A293 mutation on the GCDH gene. All patients had MRI brain scans. The basal ganglia were hyperintense on the T2/FLAIR sequences in all patients (enlarged n=3, atrophic n=2); those with enlarged basal ganglia showed restricted diffusion. This was seen in the 3 children who presented in crises. Delayed myelination was seen in 1 child. Other abnormalities included: abnormal signal in the cerebral peduncles/central tegmental tract n=4, enlarged temporal fossa n=5, cortical atrophy n=3. All patients were treated with L-carnitine and dietary modification. Three patients required anti-epileptics and 2 required L-dopa for dystonia. Two patients had a static clinical course, 1 has gained milestones and 2 have shown progression. Conclusion Key clinical features in our patients include a child presenting in acute encephalopathic crises follow, neuro-regression, and macrocephaly. We identified unusual imaging features – abnormal signal in the central tegmental tract/cerebral peduncles. South Africa does not have a neonatal screening programme for Glutaric Aciduria. It is crucial to have a high index of suspicion as early diagnosis/intervention improves outcome. To describe the clinical profile, diagnosis and treatment of patients with Type 1 Glutaric Aciduria. A retrospective review of children with a confirmed diagnosis at Inkosi Albert Luthuli Hospital, South Africa. We identified 5 children (3 females, 2 Males) during the period 2007–2014. The mean age at diagnosis was 11 months (range 7–22 months). Three patients presented in acute encephalopathic crises. Two patients had an insidious presentation-developmental delay (n=1) and hemiparesis (n=1). The clinical findings on presentation were hyptonia (n=4), hemiparesis (n=1) and macrocephaly (n=5). Two children had a history of pre-morbid developmental delay. Four children had neuro-regression on presentation. Other complications included seizures (n=3), dystonia (n=2). Urine organic acid screens showed elevated glutaric acid in all patients. Of the 4 patients tested, all were positive for the common A293 mutation on the GCDH gene. All patients had MRI brain scans. The basal ganglia were hyperintense on the T2/FLAIR sequences in all patients (enlarged n=3, atrophic n=2); those with enlarged basal ganglia showed restricted diffusion. This was seen in the 3 children who presented in crises. Delayed myelination was seen in 1 child. Other abnormalities included: abnormal signal in the cerebral peduncles/central tegmental tract n=4, enlarged temporal fossa n=5, cortical atrophy n=3. All patients were treated with L-carnitine and dietary modification. Three patients required anti-epileptics and 2 required L-dopa for dystonia. Two patients had a static clinical course, 1 has gained milestones and 2 have shown progression. Key clinical features in our patients include a child presenting in acute encephalopathic crises follow, neuro-regression, and macrocephaly. We identified unusual imaging features – abnormal signal in the central tegmental tract/cerebral peduncles. South Africa does not have a neonatal screening programme for Glutaric Aciduria. It is crucial to have a high index of suspicion as early diagnosis/intervention improves outcome.