Abstract
A 4-month-old infant with hypotonia and macrocephaly was diagnosed as having 3-hydroxy-3-methylglutaric aciduria, using gas chromatography and mass spectrometry and confirmatory enzyme studies. The same diagnosis was made on his asymptomatic non-indentical twin. Examination of the pedigree is consistent with an autosomal recessive mode of inheritance. Dietary treatment improved the symptoms of the propositus, but did not prevent episodes similar to Reye's syndrome in both twins. One such episode closely followed immunisation and our experience suggests that children with this disorder should be observed carefully following immunisation. These episodes were accompanied by an overflow of a wide range of abnormal metabolites.
Examination of the urine for organic acids should be considered in infants with unexplained hypotonia and macrocephaly, especially if accompanied by abnormal biochemical indices.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Applegarth DA, Macleod PM, Toone JR, Kirby LT, Maclean JR, Mamer OA, Montgomery JA (1979) Organic acids and Reye's syndrome. Lancet I:1147
Chalmers RA, Lawson AM (1982) Organic acids in man—the analytical chemistry, biochemistry and diagnosis of the organic acidurias. Chapman and Hall, London New York
Clinkenbeard KD, Reed WD, Mooney RA, Lane MD (1975) Intracellular localisation of 3-hydroxy-3-methylglutaryl coenzyme. A cycle enzymes in liver. J Biol Chem 250:3108–3116
Divry P, Rolland MO, Teyssier J, Cotte J, Fernandes MCF, Almeida IT, Silveira C (1981) 3-Hydroxy-3-methyglutaric aciduria combined with 3-methylglutaconic aciduria: A new case. J Inherited Metab Dis 4:173–174
Duran M, Schutgens RB, Ketel A, Heymans H, Berntssen MW, Ketting D, Wadman SK (1979) 3-Hydroxy-3-methylglutaryl coenzyme A lyase deficiency: Postnatal management following prenatal diagnosis by analysis of maternal urine. J Pediatr 95:1004–1007
Faull K, Bolton P, Halpern B, Hammond J, Danks DM, Hähnel R, Wilkinson SP, Wysocki SJ, Masters PL (1976) Patient with defect in leucine metabolism. N Engl J Med 294:1013
Faull KF, Bolton PD, Halpern B, Hammond J, Danks DM (1976) The urinary organic acid profile associated with 3-hydroxy-3-methylglutaric aciduria. Clin Chim Acta 73:553–559
Francois B, Bachmann C, Schutgens RBH (1981) Glucose metabolism in a child with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. J Inherited Metab Dis 4:163–164
Gibson KM, Sweetman L, Nyhan WL, Page TM, Greene C, Cann HM (1982) 3-Hydroxy-3-methylglutaric aciduria: A new assay of 3-hydroxy-3-methylglutaryl-CoA lyase using high performance liquid chromatography. Clin Chim Acta 126:171–181
Leupold D, Bojasch M, Jakobs C (1982) 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency in an infant with macrocephaly and mild metabolic acidosis. Eur J Pediatr 138:73–76
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
McGarry JD, Foster DW (1980) Regulation of hepatic fatty acid oxidation and ketone body production. Ann Rev Biochem 49:395–420
Norman EJ, Denton MD, Berry HK (1982) Gas- Chromatographic/Mass Spectrometric detection of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency in double first cousins. Clin Chem 28:137–140
Robinson BH, Oei J, Sherwood WG, Slyper AH, Heininger J, Mamer OA (1980) Hydroxymethylglutaryl CoA lyase deficiency: Features resembling Reye Syndrome. Neurology 30:714–718
Schutgens RB, Heymans H, Ketel A, Veder HA, Duran M, Ketting D, Wadman SK (1979) Lethal hypoglycaemia in a child with a deficiency of 3-hydroxy-3-methylglutarylcoenzyme A lyase. J Pediatr 94:89–91
Shilkin R, Wilson G, Owles E (1981) 3-Hydroxy-3-methylglutaryl Coenzyme A lyase deficiency: Follow-up of first described case. Acta Paediatr Scand 70:265–268
Tracey BM, Stacey TE, Chalmers RA (1983) Urinary and plasma organic acids in dizygotic twin siblings with 3-hydroxy-3-methylglutaric aciduria, studied by gas chromatography and mass spectrometry using fused silica capillary columns. J Inherited Metab Dis 6 [Suppl] 2: 125–126
Truscott RJW, Halpern B, Wysocki SJ, Hähnel R, Wilcken B (1979) Studies on a child suspected of having a deficiency in 3-hydroxy-3-methylglutaryl-CoA lyase. Clin Chim Acta 95:11–16
Wysocki SJ, Hähnel R (1976) 3-Hydroxy-3-methylglutaric aciduria: 3-hydroxy-3-methylglutaryl-Coenzyme A lyase levels in leucocytes. Clin Chim Acta 73:373–375
Wysocki SJ, Hähnel R (1976) 3-Hydroxy-3-methylglutaric aciduria: Deficiency of 3-hydroxy-3-methylglutaryl Coenzyme A lyase. Clin Chim Acta 71:349–351
Wysocki SJ, Wilkinson SP, Hähnel R, Wong CYB, Panegyres PK (1976) 3-Hydroxy-3-methylglutaric aciduria, combined with 3-methylglutaconicaciduria. Clin Chim Acta 70:399–406
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stacey, T.E., de Sousa, C., Tracey, B.M. et al. Dizygotic twins with 3-hydroxy-3-methylglutaric aciduria; unusual presentation, family studies and dietary management. Eur J Pediatr 144, 177–181 (1985). https://doi.org/10.1007/BF00451909
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00451909