Abstract
This report describes three brothers belonging to a consanguineous family suffering from a progressive neurological disorder associated with L-2-hydroxyglutaric aciduria. Clinically this disorder is characterized by childhood onset, pyramidal signs, cerebellar and pseudobulbar syndromes and epilepsy. Pathological examination of the brain in the oldest patient, who died at the age of 30 years, showed bilateral and diffuse spongiosis with notable cystic cavitations of the cerebral white matter without abnormal storage in neurons and glial cells. We consider that these findings are related to L-2 hydroxyglutaric aciduria. To our knowledge this present case represents the first to be reported with neuropathological examination.
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References
Barth PG, Hoffmann GF, Jaeken J, Lehnert W, Hanefeld F, Van Gennip AH, Duran M, Valk J, Schutgens RBH, Trefz FK, Reimann G, Hartung HP (1992) L-2-Hydroxyglutaric acidemia: a novel inherited neurometabolic disease. Ann Neurol 32: 66–71
Bauman ML, Kemper T (1982) Morphologic and histoanatomic observations of the brain in untreated human phenylketonuria. Acta Neuropathol (Berl) 58: 55–63
Bohm N, Uy J, Kiebling M, Lehnert W (1982) Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II), congenital polycystic kidneys, symmetric warty dysplasia of the cerebral cortex in two newborn brothers. II. Morphology and pathogenesis. Eur J Pediatr 139: 60–65
Bruton CJ, Corsellis JAN, Russel A (1970) Hereditary hyperammonaemia. Brain 93: 423–434
Canavan MM (1931) Schilder's encephalitis periaxialis diffusa. Arch Neurol Psychiatry 25: 299–308
Dobyns WB (1989) Agenesis of the corpus callosum and gyral malformations are frequent manifestations of nonketotic hyperglycinemia. Neurology 39: 817–820
Duchen LW, Jacobs JM (1984) Nutritional deficiencies and metabolic disorders. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greefield neuropathology, 4th edn. Edward Arnold, London, pp 573–626
Duran M, Kamerling JP, Bakker HD, Van Gennip AH, Wadman SK (1980) L-2-Hydroxyglutaric aciduria: an inborn error of metabolism? J Inherit Metab Dis 3: 109–112
Egger J, Pincott JR (1984) Cortical subacute necrotizing encephalopathy. A study of 2 patients with mitochondrial dysfunction. Neuropediatrics 15: 150–158
Harding BN, Leonard JV, Erdobazi M (1984) Ornithine carbamyl transferase deficiency: a neuropathological study. Eur J Pediatr 141: 215–220
Heyes MP (1987) A role for quinolinic acid in the neuropathology of glutaric aciduria type 1. 1. Can J Neurol Sci 14: 441–443
Hoffmann GF, Barth P, Lahnert W, Duran M, Hunneman DH, Jaeken J, Rating D, Schutgens RB, Voss W, Hanefeld F (1991) Progressive ataxia and mental retardation associated with leucodystrophy in 4 patients with L-2-hydroxyglutaric aciduria. European society of pediatric research. Zurich. (personnal commun)
Jaeken J, Willekens H, Corbeel L (1988) Leucodystrophy associated with hyperlysinorhachia and 2-hydroxyglutaric aciduria (abstract). Pediatr Res 24: 266
Kabachi N, Larnaout A, Rabier D, Jacobs C, Belal S, Hentati F, Parvey P, Bardet J, Ben Hamida M, Mebazaa A, Kamoun P (1993) Familial encephalopathy and L-2 hydroxyglutaric aciduria. J Inherit Metab Dis 16: 893
Lehnert W, Hoffmann GF (1990) L-2-Hydroxyglutaric aciduria: diagnosis, clinical picture and biochemical investigations in two cases. Abstracts of the Vth International Congress on Inborn errors of metabolism. Pacific Grove, Calif., June 1–5, 1990. (personnal commun)
Leibel RL, Shih VE, Goodman SI, Bauman LM, McCabe ERB, Zwerdling RG, Bergman I, Costello C (1980) Glutaric acidemia: a metabolic disorder causing progressive choreoathetosis. Neurology 30: 1163–1168
Masters CL, Richardson EP Jr (1978) Subacute spongioform encephalopathy (Creutzfeldt-Jacob disease). The nature and progression of spongioform change. Brain 101: 333–344
Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH (1962) A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics 29: 764–779
Stokke O, Goddman SI, Moe PG (1976) Inhibition of brain glutamate decarboxylase by glutarate, glutaconate and 3-hydroxyglutarate: explanation for the symptoms in glutaric aciduria? Clin Chim Acta 66: 411–415
Walter GF, Brucher JM, Martin JJ, Ceuterick C, Pilz P, Freund M (1986) Leigh's disease. Several nosological entities with an identical histopathological complex? Neuropathol Appl Neurobiol 12: 95–107
Zenon M, Sfaello NA, Chamoles LE, Jorge MI, Duran M (1992) L-2-Hydroxyglutaric aciduria: 3 new cases (abstract). Pediatr Neurol 8: 395
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Larnaout, A., Hentati, F., Belal, S. et al. Clinical and pathological study of three Tunisian siblings with L-2-hydroxyglutaric aciduria. Acta Neuropathol 88, 367–370 (1994). https://doi.org/10.1007/BF00310381
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DOI: https://doi.org/10.1007/BF00310381