FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022069061> ?p ?o ?g. }

• W2022069061 endingPage "341" @default.
• W2022069061 startingPage "339" @default.
• W2022069061 abstract "3-Hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) lyase is an enzyme that catalyzes the final step in leucin degradation in the mitochondria. It is converted to acetyl-CoA and acetoacetic acid. Being the last products of this reaction, acetyl-CoA and acetoacetic acid are important in producing energy during periods of fasting and intercurrent illness. 3-Hydroxy-3-methylglutaryl coenzyme-A lyase deficiency is characterized by recurrent episodes of vomiting, hypotonia, lethargy, seizures or coma, metabolic acidosis, hyperammonemia, and nonketotic hypoglycemia. These episodes often occur during an intercurrent infection. Some patients also have hepatomegaly and elevated serum transaminase (1). 3-Hydroxy-3-methylglutaryl coenzyme-A lyase enzyme deficiency is a rare cause of hepatomegaly. In this report, we described a patient with hepatomegaly and elevated serum transaminase at presentation who was diagnosed as having HMG-CoA lyase enzyme deficiency. CASE REPORT A 7-month-old female patient was admitted to our unit with abdominal distention noted 2 months previously by the mother. Parental consanguinity was not described; however, the parents were living in the same district and they were healthy. The first child was a 6-year-old healthy female. The second child died at 2 months of age at home, and the cause of death was unknown. Our patient is the third child of the family. Prenatal and postnatal medical history was unremarkable. She had not previously experienced any significant illness. The patient was well developed. Her weight was 8.5 kg (50–75th percentile), her height was 69 cm (50–75th percentiles), and neurologic development was normal. On physical examination, the liver was firmly enlarged 4 cm below the right costal margin, and the spleen was palpated 3 cm. Initial biochemical investigations revealed the following: serum glutamic pyruvic transaminase level was 76 IU/L (normal, <40 IU/L); serum glutamic oxaloacetic transaminase level was 82 IU/L (normal, <40 IU/L). γ-Glutamyl transpeptidase and alkaline phosphatase were within normal limits. Alpha-1 antitrypsin, hepatitis B markers, anti-HAV (hepatitis A virus) immunoglobulin M, and TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpesvirus) immunoglobulin M values were interpreted as negative. Abdominal ultrasonography did not indicate any pathologic findings, and funduscopic examination revealed normal optic disks and retinal vasculature. Histopathologic examination of the liver revealed fatty changes and minimal parenchymal damage. During follow-up, the patient had vomiting, lethargy, and high fevers 3 weeks later. On physical examination, her general appearance was not well, and her rectal temperature was 39°C. Somnolence and hepatosplenomegaly was noted, and her respirations were deep and sighing. When a detailed medical history was taken, we learned that her urine had an unusual odor since she was 5 months old, and the mother reported that during periods when she was not fed frequently, she had episodes of weakness and pallor. Laboratory studies revealed the following: hemoglobulin: 6.8 g/dL; hematocrit: 22%; white blood cell count: 7,100 cells/mm 3 ; platelet count: 381,000/mm 3 ; blood glucose level: 40 mg/dL; arterial blood pH; 7.24; bicarbonate: 14.3 mEq/L; base excess: −11.6; blood ammonia level: 400 μg/dL (normal, <195 μg/dL); uric acid: 11 mg/dL; serum glutamic oxaloacetic transaminase level: 80 IU/L; and serum glutamic pyruvic transaminase level: 76 IU/L. γ-Glutamyl transpeptidase and alkaline phosphatase levels were normal, and prothrombin time was normal. Urine pH was 6.5, and results of dinitrophenylhydrazine spot test of the urine were negative for ketone bodies. When hyperammonemia and metabolic acidosis was noted, in doubt of a metabolic disease, quantitative serum amino acid chromatography results were evaluated and found to be normal, whereas urine amino acid chromatography results revealed mild generalized aminoaciduria. The gas chromatographic and mass spectrometric urinary organic acid evaluation showed marked elevation of the leucine metabolites 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-methylglutaric, and 3-hydroxy-isovaleric acids. The diagnosis of HMG-CoA lyase deficiency was confirmed by enzyme analyses in leukocytes, which were 0 nmol · min −1 · mg protein −1 (control, 17.4 nmol · min −1 · mg protein −1 ). Enzymatic analyses were performed by Dr. R. Wanders at the University of Amsterdam, Department of Genetic Metabolic Diseases. The patient was hydrated and treated with a continuous glucose infusion. Bicarbonate was administered to correct acidosis. Intravenous carnitine (150 mg · kg −1 · 24 h −1 ) was started. The patient responded well to this treatment, rapidly regaining normal alertness. Concentrations of ammonia levels and blood glucose levels rapidly returned to normal after this treatment. She was placed on a low-fat (20%) and leucine-restricted formula (80 mg/kg daily), and l -carnitine (100 mg/kg daily) treatment was continued. Hepatic enzyme levels gradually returned to normal values within 6 months, and hepatomegaly was not noted. Thirteen months after diagnosis, the patient had two mild episodes after experiencing viral infections that responded within 36 to 48 hours to treatment with intravenous fluids and glucose. She is now 20 months old with normal growth and development. DISCUSSION 3-Hydroxy-3-methylglutaryl coenzyme-A lyase deficiency is a rare inborn error of ketogenesis and leucine catabolism. The disease was first described by Faull et al. (2) in 1976 and Wysocki et al. (3) in 1986. Major findings are recurrent episodes that are usually triggered by infection or fasting and are characterized by metabolic acidosis, hyperammonemia without ketosis, hypoglycemia, and elevation of the organic metabolites 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-methylglutaric, and 3-hydroxy-isovaleric acids in urine (Fig. 1) (4,5). Clinical features are similar to those of Reye syndrome, including hepatic dysfunction, vomiting, seizures, lethargy, and encephalopathy (6–8). The disease is inherited in an autosomal recessive pattern. Approximately 30% of patients become symptomatic in the neonatal period, and approximately 60% become symptomatic between 3 and 12 months of age, in the early infantile period. In the neonatal period, the disease is fatal unless treated promptly (1).FIG. 1.: Metabolic interrelation of the leucine catabolic pathway and the cycle of kegogenesis. The site of the metabolic defects in patients with HMG-CoA lyase deficiency is indicated by the cross-hatched box. 3-HIVA, 3-hydroxyisovaleric acid; 3-MCG, 3 methylcrotonylglycine; 3-MGC, 3-methylglutaconic acid; 3-MGR, 3-methylglutaric acid; 3-HMG, 3-hydroxy-3-methylglutaryl.Ketonuria is not present in HMG-CoA lyase deficiency, and this finding is helpful in the differentiation from other organic acidemias. 3-Hydroxy-3-methylglutaryl coenzyme-A lyase enzyme activity in cultured fibroblasts and lymphocytes establishes the definitive diagnosis. Restriction of protein and fat intake and carnitine therapy is recommended for long-term management of these patients. Frequent and serious acute metabolic deterioration periods reduce the treatment success for the disease (5,9). In the literature, most reported patients have been admitted to the hospital because of findings of hypoglycemia, metabolic acidosis, or encephalopathy (4,8,10,11). However, our patient was admitted because of abdominal distention and the initial findings of hepatomegaly and elevated transaminase levels. Hepatic biopsy was performed to evaluate hepatomegaly, and the patient was followed up from the outpatient clinic. During this follow-up period, after a viral infection, she arrived at the emergency unit with somnolence, hypoglycemia, metabolic acidosis, and hyperammonemia. She was well developed, and neither seizures nor periods of vomiting were described. Serum amino acid chromatography was normal, and the diagnostic possibility of fatty acid oxidation defects and urea cycle defects were excluded. The infant was in a catabolic state with hypoglycemia and hyperammonemia; however, ketone bodies in urine were not present. Because the disease is characterized by the absence of significant ketonuria, HMG-CoA lyase deficiency was the primary diagnosis. Urinary organic acid evaluation revealed marked elevation of the leucine metabolites 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-methylglutaric, and 3-hydroxy-isovaleric acids, and a definitive diagnosis of HMG-CoA lyase deficiency was established. Inborn errors of metabolism that present in this manner include urea cycle defects (12), disorders of fatty acid oxidation (13), and organic acidemias (5). In both systemic carnitine deficiency and HMG-CoA lyase deficiency, acyl-CoA compounds accumulate. Acyl-CoA compounds pass through mitochondrial membranes by means of carnitine. Since carnitine binds acyl compounds, administration of carnitine may reduce these abnormal metabolites. In most of the organic acidemias, carnitine is administered in 100-to 200-mg/kg doses four times (4,5,11,14). Our patient also received carnitine as stated in literature, and clinical and laboratory improvement was established. In conclusion, because early diagnosis leads to success in treatment and prenatal diagnosis is possible, in our country, where consanguineous marriages are common, HMG-CoA lyase deficiency should be considered in the differential diagnosis of infants with hepatomegaly, encephalopathy, and metabolic acidosis at presentation." @default.
• W2022069061 created "2016-06-24" @default.
• W2022069061 creator A5028351714 @default.
• W2022069061 creator A5048328144 @default.
• W2022069061 creator A5067536801 @default.
• W2022069061 creator A5076247713 @default.
• W2022069061 date "2001-09-01" @default.
• W2022069061 modified "2023-10-10" @default.
• W2022069061 title "A Rare Cause of Hepatomegaly: 3-Hydroxy-3-Methylglutaryl Coenzyme-A Lyase Deficiency" @default.
• W2022069061 cites W1973101359 @default.
• W2022069061 cites W1979072930 @default.
• W2022069061 cites W1983007547 @default.
• W2022069061 cites W2027873589 @default.
• W2022069061 cites W2032397781 @default.
• W2022069061 cites W2052023078 @default.
• W2022069061 cites W2066607752 @default.
• W2022069061 cites W2090577334 @default.
• W2022069061 cites W2137680310 @default.
• W2022069061 cites W4301347062 @default.
• W2022069061 doi "https://doi.org/10.1097/00005176-200109000-00022" @default.
• W2022069061 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11593134" @default.
• W2022069061 hasPublicationYear "2001" @default.
• W2022069061 type Work @default.
• W2022069061 sameAs 2022069061 @default.
• W2022069061 citedByCount "8" @default.
• W2022069061 countsByYear W20220690612015 @default.
• W2022069061 countsByYear W20220690612020 @default.
• W2022069061 crossrefType "journal-article" @default.
• W2022069061 hasAuthorship W2022069061A5028351714 @default.
• W2022069061 hasAuthorship W2022069061A5048328144 @default.
• W2022069061 hasAuthorship W2022069061A5067536801 @default.
• W2022069061 hasAuthorship W2022069061A5076247713 @default.
• W2022069061 hasConcept C126322002 @default.
• W2022069061 hasConcept C134018914 @default.
• W2022069061 hasConcept C134651460 @default.
• W2022069061 hasConcept C181199279 @default.
• W2022069061 hasConcept C2777269803 @default.
• W2022069061 hasConcept C2779123261 @default.
• W2022069061 hasConcept C55493867 @default.
• W2022069061 hasConcept C71924100 @default.
• W2022069061 hasConcept C86803240 @default.
• W2022069061 hasConceptScore W2022069061C126322002 @default.
• W2022069061 hasConceptScore W2022069061C134018914 @default.
• W2022069061 hasConceptScore W2022069061C134651460 @default.
• W2022069061 hasConceptScore W2022069061C181199279 @default.
• W2022069061 hasConceptScore W2022069061C2777269803 @default.
• W2022069061 hasConceptScore W2022069061C2779123261 @default.
• W2022069061 hasConceptScore W2022069061C55493867 @default.
• W2022069061 hasConceptScore W2022069061C71924100 @default.
• W2022069061 hasConceptScore W2022069061C86803240 @default.
• W2022069061 hasIssue "3" @default.
• W2022069061 hasLocation W20220690611 @default.
• W2022069061 hasLocation W20220690612 @default.
• W2022069061 hasOpenAccess W2022069061 @default.
• W2022069061 hasPrimaryLocation W20220690611 @default.
• W2022069061 hasRelatedWork W1422277532 @default.
• W2022069061 hasRelatedWork W1496234280 @default.
• W2022069061 hasRelatedWork W1957781043 @default.
• W2022069061 hasRelatedWork W2039521230 @default.
• W2022069061 hasRelatedWork W2087917372 @default.
• W2022069061 hasRelatedWork W2170953939 @default.
• W2022069061 hasRelatedWork W2464172483 @default.
• W2022069061 hasRelatedWork W2777691310 @default.
• W2022069061 hasRelatedWork W4206482165 @default.
• W2022069061 hasRelatedWork W966738943 @default.
• W2022069061 hasVolume "33" @default.
• W2022069061 isParatext "false" @default.
• W2022069061 isRetracted "false" @default.
• W2022069061 magId "2022069061" @default.
• W2022069061 workType "article" @default.