Management and long-term evolution of a patient with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency

Abstract

Background3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error of metabolism characterized by recurrent metabolic crises caused by fasting, intercurrent illness and excessive physical exercise. Non ketotic hypoglycemia is normally the cause of primary symptoms but without an immediate treatment the illness can evolve into a worsening metabolic state resembling the Reye’s syndrome that may cause the patient’s death. We report a case with some clinical and therapeutic features not previously described.Case presentationPatient with HMG-CoA lyase deficiency whom after diagnosis at 2 years of age was re-admitted 12 years later, after severe metabolic decompensation following consumption of alcohol. Despite a quick correction of hypoglycemia, within the following few hours, the patient fell into a coma. Suspecting intracranial hypertension (ICH), the patient required mechanical ventilation. Although liver cytolysis was minimal, hyperamoniemia reached 1394 μmol/L, returning to normal, a few hours after administering sodium phenylacetate and sodium benzoate, whose use has not been reported in these patients. Brain edema was evidenced in the computed tomography and by the magnetic resonance imaging that determined that the edema was cytotoxic, as quantified with the restriction of diffusion in the apparent diffusion coefficient map. During the recovery of the ICH, we belatedly, detected vasospasm moderate-severe that was treated with nimodipine. Currently, the patient maintains clinical normality.ConclusionsThe alcohol consumption must be avoided in patients with HMG-CoA lyase deficiency. In our patient hyperamoniemia was effectively treated with sodium phenylacetate and sodium benzoate. Magnetic resonance imaging showed and quantified the cytotoxic brain edema. Belatedly, a cerebral vasospasm was an additional mechanism of cerebral injury. None of these observations has been previously reported.

Coma en adulto joven de causa inhabitual

“…El déficit de 3-HMGL es un error congénito del metabolismo de la leucina y la cetogénesis producido por mutaciones en el gen HMGCL (Hidroximetilglutaril-CoA liasa) localizado en el cromosoma 1p36.11 [1][2][3][4][5][6] . El diagnóstico puede establecerse por el análisis de ácidos orgánicos en orina (elevación de 3-Hidroxi-3-Metilglutárico, 3-Metilglutarico, 3-MetilGlutaconico y 3 hidroxiIsovalérico) y acilcarnitina en suero (niveles elevados de 3-hidroxi-isovalerilcarnitina y disminución de la concentración de carnitina libre) [1][2][3][4][5]8 .…”

“…El diagnóstico puede establecerse por el análisis de ácidos orgánicos en orina (elevación de 3-Hidroxi-3-Metilglutárico, 3-Metilglutarico, 3-MetilGlutaconico y 3 hidroxiIsovalérico) y acilcarnitina en suero (niveles elevados de 3-hidroxi-isovalerilcarnitina y disminución de la concentración de carnitina libre) [1][2][3][4][5]8 . Más del 60 % de los casos son diagnosticados antes del primer año de vida 1,3,4,6 . Generalmente se presenta con episodios recurrentes de hipoglucemia grave [1][2][3][4] .…”

Hepatic Manifestations of 3-Hydroxy-3-Methylglutaryl-Coenzyme-A Lyase Deficiency in Saudi Patients: Experience of a Tertiary Care Center

“…The hepatic involvement usually improves after protein and diet restriction. 20,21 Anticipation of HMGCL deficiency in early age and starting the appropriate diet leads to good prognosis in term of systemic symptoms, including the liver. 22 To date, there are no studies describing the genotype-phenotype correlation in patients with this disease in regard to the liver-related findings in details.…”

When A Common Symptom of a Neonate Become an Unusual Diagnosis: A Case Report Of HMG-Coa Lyase Deficiency with a Novel Mutation

“…3-hydroxy-3 methylglutaryl-coenzyme A (HMG CoA) lyase deficiency is a rare autosomal recessive inborn error of metabolism characterized by impairment of ketogenesis and leucine catabolism resulting in attacks of metabolic acidosis, nonketotic hypoglycemia, and a characteristic pattern of elevated urinary organic acids: 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3methylglutaric, and 3-hydroxyisovaleric acids (1). The disease was first described by Faull in 1976 and has an estimated prevalence of less than 1 in 100.000 live births.…”