3‐hydroxy‐3‐methylglutaryl‐coenzyme a lyase deficiency: Report of five new patients

Gibson, K. Michael; Breuer, Joseph; Kaiser, Klaudia; Nyhan, William L.; McCoy, Ernest E.; Ferreira, Patrick; Greene, Carol L.; Blitzer, Miriam G.; Shapira, Emmanuel; Reverte, F.; Conde, Carlos Fernández; Bagnell, Philip C.; Cole, David E. C.

doi:10.1007/bf01800058

Cited by 52 publications

(32 citation statements)

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“…Initial symptoms may include poor feeding, vomiting, diarrhea, followed by further complication as hypotonia, hypothermia, lethargy, cyanosis and apnea. (Schutgens et al, 1979;Gibson et al, 1988a;Gibson et al, 1988b). In some cases the progresive lowered state of consciousness leads to coma and subsequent death (Wysocki et al, 1986).…”

Section: Acute Crisismentioning

confidence: 99%

“…Chronic complications are uncommon but include: hepatomegalia, macrocephalia (Gibson et al, 1988b;Stacey et al, 1985) microcephalia (Lisson et al, 1981) and delayed development (Gibson et al, 1994). It has been reported that organs such as the brain, the liver and occasionally the pancreas and the heart are affected (Gibson et al, 1994;Leung et al, 2009;Muroi et al, 2000a;Urganci et al, 2001;Wilson et al, 1984;Zafeiriou et al, 2007;Zoghbi et al, 1986).…”

Section: Chronic Complicationsmentioning

confidence: 99%

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HMG–CoA Lyase Deficiency

Puisac¹,

Arnedo²,

Gil-Rodríguez³

et al. 2011

Advances in the Study of Genetic Disorders

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Section: Acute Crisismentioning

confidence: 99%

Section: Chronic Complicationsmentioning

confidence: 99%

HMG–CoA Lyase Deficiency

Puisac¹,

Arnedo²,

Gil-Rodríguez³

et al. 2011

Advances in the Study of Genetic Disorders

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“…Abbreviations: HMG = 3-hydroxy-3-methylglutaric; HMG-CoA = 3-hydroxy-3-methylglutaryl-CoA; 3-MCR-CoA = 3-methylcrotonyl-CoA; 3-MGC = 3-methylglutaconic; 3-MGC-CoA = 3-methylglutaconyl-CoA; 3-MG = 3-methylglutaric; M-5-P = mevalonate-5-pyrophosphate published in recent years [15,32,38]. In contrast, publications on isolated deficiencies of 3-methylcrotonyl-CoA carboxylase (3-MCR-CoA carboxylase: E.C.…”

Section: Correspondence To: K M Gibsonmentioning

confidence: 99%

Multiple respiratory chain abnormalities associated with hypertrophic cardiomyopathy and 3-methylglutaconic aciduria

Ibel¹,

Endres²,

Hadorn³

et al. 1993

Eur J Pediatr

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In a 4.5-month-old boy presenting with marked muscular hypotonia in the neonatal period, hepatomegaly, cardiac hypertrophy, recurrent hypoglycemia, metabolic acidosis, and secondary carnitine deficiency, there was a considerable urinary excretion of 3-methylglutaconic and 3-methylglutaric acid. Estimation of 3-methylglutaconyl-CoA hydratase, 3-hydroxy-3-methylglutaryl-CoA lyase and initial enzymatic steps of cholesterol biosynthesis in cultured fibroblasts and in different tissues postmortem revealed no enzyme deficiency. Analyses of the respiratory chain in postmortem tissues demonstrated severe impairment of complex I (NADH ubiquinone oxidoreductase) and complex IV (cytochrome c oxidase) activities in skeletal muscle and reduced complex IV activity in heart.

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“…The disorder is characterized biochemically by greatly increased concentrations of several characteristic organic acids in blood and urine, including 3-hydroxy-3-methylglutaric and, 3-methyiglutaric acid, 3-methylglutaconic acid and 3-hydroxyisovaleric acid, and by demonstrably deficient activity of HMG CoA lyase activity in blood leukocytes and cultured skin fibroblasts H~ihnel, 1976, 1986;Stacey et al, 1985;Gibson et al, 1988). The disorder may be severe and potentially lethal with patients presenting with recurrent episodes that resemble Reye syndrome, with severe hypoglycaemia, hyperammonaemia, encephalopathy and metabolic acidosis, and permanent neurological damage occurring in some patients surviving late-treated episodes.…”

mentioning

confidence: 99%

Prenatal diagnosis of 3‐Hydroxy‐3‐methylglutaric aciduria by GC‐MS and enzymology on cultured amniocytes and chorionic villi

Chalmers

Tracey

Mistry

et al. 1989

J of Inher Metab Disea

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, Middlesex. UK. 3-Hydrory-3-methylglutaric (HMO) aciduria is a disorder of L-leuc-ine metabolism and ketone body biosynthesis characteriaed by recurrent acute life-threatening episodes resembling Reye's syndrome. Prenatal diagnosis was requested by the parents of a child with this condition and was carried out by amniocenteeis at 16 weeks' gestation. Amniotic fluid concentrations (capillary GC and GC-HS) (Umole/L) were for W G 34.6 (N=1.21+0.38), 3-hydroryisovalerate (HIV) 33.9 (N=4.78f1.91). 3-methylglutaconate (3MAG) 31.7 (N=0.62-0.90) and 3-methylglutarate(3MG) 1.23 (N=0.12-0.26) consistent with an affected fetus. Termination was carried out on the basis of these data. The diagnosis was confirmed immediately by analysis of fetal plasma for organic acid6:concentra-tions of HMG, HIV, 3MAG and 3MG were 67.3, 36.9, 31.3 and 11.31lmoles/L respectively. Subsequent enzymology on cultured amoiocytes gave mean results for isovalerate incorporation into protein (pmol/h/mg protein) of 48 compared to simultaneous controls of 252; direct WIG CoA lyaS-3 activity (moles ilMG CoA removed/min/mg protein) was 0.05 compared to simultaneous controls of 9.16. Direct HMG CoA lyase measurements on chorionic villus tissue obtained at termination gave mean activities of 0.87 compared to controls of 8.04. These results provide the first prenatal diagnosis of HMG aciduria, demonstrate the rapid, accurate and unambiguous diagnosis at 16 weeks using direct GC-MS analysis of amniotic fluid and indicate the suitability of chorionic villus biopsy for future earlier (9 weeks) prenatal diagnoses of this condition. ORGANIC ACIDURIA IN PATIENTS WITH GLYCOGWOSIS TYPE I. Intrigued by the persistent growth retardation of some glucose-6-phosphatase-deficient patients, we investigated the urinary excretion of lactate, 2-oxoglutarate and citrate, reflecting organic acid overproduction , and glycerol reflecting impaired gluconeogenesis, in 17 patients with type I A and 1 patient with type IB glycogenosis. The urine was collected during 8-10 successive days twice daily. The mean lactate-creatinine ratio (mM/mM) ranged from 0.27 to 11.17 (normal 0.010 to0.058, N=36) in 5 patients with a height < P3. The lactate excretion in these patients varied considerably during successive days and less during gastric drip feeding at night. The mean lactate-creatinine ratio in the other patients was more constant and ranged from 0.04 to 0.34, The mean 2-oxoglutarate-creatinine ratio (mM/mM) ranged from 0.17 to 0.84 (normal 0 to 0.05, N=15) in 4 of 5 growth retarded patients. In the other patients it ranged from 0.01 to 0.43. The 2-oxoglutarate excretion per patient varied little. The mean citrate-creatinine ratio (mM/mM) ranged from 0.03 to 0.84 in all patients (normal 0.12 to 0.73, N=15). The mean glycerol-creatinine ratio (mM/mM) ranged from 0.01 to 0.11 (normal 0.005 to 0.03, n=15). We conclude that the lactate-creatinine ratio reflects both the adequacy of the dietary treatment and the severity of the disease, whereas the 2-oxoglutarate-creatinine ratio reflects...

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3‐hydroxy‐3‐methylglutaryl‐coenzyme a lyase deficiency: Report of five new patients

Abstract: Five new patients are reported and the pathogenesis of the hypoglycaemia without ketogenesis is discussed. This report extends a recent review.

Cited by 52 publications

References 16 publications

HMG–CoA Lyase Deficiency

HMG–CoA Lyase Deficiency

Multiple respiratory chain abnormalities associated with hypertrophic cardiomyopathy and 3-methylglutaconic aciduria

Prenatal diagnosis of 3‐Hydroxy‐3‐methylglutaric aciduria by GC‐MS and enzymology on cultured amniocytes and chorionic villi

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