Journal of Inherited Metabolic Disease

, Volume 31, Supplement 3, pp 511–515 | Cite as

Incidence of 3-hydroxy-3-methylglutaryl-coenzyme A lyase (HL) deficiency in Brazil, South America

  • C. R. Vargas
  • A. Sitta
  • G. Schmitt
  • G. C. Ferreira
  • M. L. Cardoso
  • D. Coelho
  • K. M. Gibson
  • M. Wajner
Short Report


3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency (3-hydroxy-3-methylglutaric aciduria, 3-HMG) is a rare autosomal recessive inborn error of metabolism involving the final step of leucine degradation. HL is the key enzyme for the production of glucose-sparing ketone bodies for brain. Positive biochemical findings are metabolic acidosis, hyperammonaemia, and hypoketotic hypoglycaemia in the neonatal period or infancy. In the present study we report 15 Brazilian patients with HL deficiency and present their clinical and biochemical findings. Urine from all patients contained large amounts of 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-hydroxyisovaleric and 3-methylglutaric acids, and 3-methylcrotonylglycine was also observed in 13 patients. The main features at clinical presentation were hypoglycaemia (12 patients), seizures (10 patients), metabolic acidosis (9 patients), vomiting (6 patients), and hepatomegaly (5 patients). All but two patients were of Portuguese ancestry. HL deficiency comprised 7.3% of total organic acidurias detected in our laboratory during a 13-year time span, indicating a high incidence of this disorder in Brazil. Limited molecular characterization (4/15 patients only) revealed two mutations common for individuals of Portuguese/Spanish (Iberian Peninsula) ancestry (E37X and V168fs(−2)). Our findings increase the number of HL-deficient patients and reinforce the characteristic phenotypic picture of the disease. Effective dietary interventions based on mild protein restriction and avoidance of fasting and possibly alternative C5 ketone body generating therapy for this disorder may provide further impetus and rationale for expanded newborn screening of HL deficiency.


D42N Mutation Brazilian Patient Organic Aciduria Organic Acid Profile Hypoketotic Hypoglycaemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



3-hydroxy-3-methylglutaryl-CoA lyase


3-hydroxy-3-methylglutaric aciduria



This work was supported in part by grants from FAPERGS, CNPq and FIPE/HCPA – Brazil.


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Copyright information

© SSIEM 2007

Authors and Affiliations

  • C. R. Vargas
    • 1
    • 2
    • 3
  • A. Sitta
    • 1
    • 3
  • G. Schmitt
    • 1
  • G. C. Ferreira
    • 3
  • M. L. Cardoso
    • 4
  • D. Coelho
    • 1
  • K. M. Gibson
    • 5
  • M. Wajner
    • 1
    • 3
    • 6
  1. 1.Medical Genetics ServiceHCPAPorto AlegreBrazil
  2. 2.Department of AnalysisPPGCF, UFRGSPorto AlegreBrazil
  3. 3.Deparment of BiochemistryICBS, UFRGSPorto AlegreBrazil
  4. 4.Institute of Genetics Jacinto MagalhãesPortoPortugal
  5. 5.Division of Medical Genetics, Departments of Pediatrics, Pathology and Human GeneticsChildren’s Hospital of Pittsburgh and University of Pittsburgh School of MedicinePittsburghUSA
  6. 6.Serviço de Genética Médica, HCPAPorto AlegreBrazil

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