Macrocefalia como forma de presentación de la aciduria glutárica tipo 1. Importancia de un diagnóstico precoz

Introduction. The clinical manifestations of glutaric aciduria type I (GA-I) usually develop during the first two years of life as acute encephalopathic crisis leading to irreversible dystonic. Progressive macrocephaly can be an early clinical sign. We report a 9 month old patient with macrocephaly diagnosed of GA-I in the presyntomatic stage. This early diagnosis and treatment avoided the irreversible neurologic damage associated to this disease. Case report. A 9 month old male referred to the pediatrics neurology clinic because of macrocephaly with a head circumference of 51 cm (> 97 t h percentle). At birth this head circumference was 37.5 cm (97 t h percentile) and showed rapid growth during the first 4 months of life. In the physical exam there was mild hypotonia and no other neurologic alterations with normal psychomotor development. In the work up for macrocephaly urinary organic acids were determined showing a glutaric acid: 78,000 mmol/mol creatinine (normal values: 2-10); 3-hydroxyglutaric acid: 250 mmol/mol creatinine (normal values: 1-12). Cerebral magnetic resonance (MR) performed at 12 months of age showed frontotemporal atrophy with enlargement of subarachnoid spaces, a high signal in T2 in the pallidus nucleus and subdural hematomas. Genetic analysis showed a mutation S 305 L/Q 352 X in GCDH gene. L-carnitine and riboflavin supplementation and a diet with restriction of lysine and tryptophan was started. Intercurrent illnesses were treated with intravenous fluid, glucose and L-carnitine. At 3 years and 6 month of age, he had not shown any encephalopathic crisis, he had a normal psychomotor development and no dystonia. MR shows mild temporal lobe atrophy without basal ganglia alterations. Conclusions. In GA-I, macrocephaly is an early sign before other neurologic alterations. In patients with little or no neurological symptoms, early treatment may prevent the acute encephalopathic crisis and neurological deterioration, improving the prognosis and may also normalize the basal ganglia neuroradiological alterations. Urinary organic acid analysis should be performed in the work up of macrocephaly of unknown aetiology.