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Biomedical subjects

M Rimoldi

Publications and source records attributed to M Rimoldi.

At least 55 records · Page 3Linked to original sources
PubMed1990

Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes.

A 7-month-old boy died in a demented state after a clinical history characterized by generalized seizures, psychomotor deterioration, and fumaric aciduria. We found a marked deficiency of both mitochondrial and cytosolic fumarases in skeletal muscle, brain, cerebellum, heart, kidney, liver, and cultured fibroblasts. Fumarase activities were 30 to 50% compared with controls in both mitochondria and cytosol from cultured fibroblasts of the parents. Antifumarase cross-reacting material was present in negligible amounts in the patient's tissues. Our data indicate that this disease is an autosomal recessive encephalopathy, due to a single mutation affecting the gene encoding both forms of the enzyme.

Acids↗
PubMed1989

Normalization of short-chain acylcoenzyme A dehydrogenase after riboflavin treatment in a girl with multiple acylcoenzyme A dehydrogenase-deficient myopathy.

A 12-year-old girl was shown to have carnitine-deficient lipid storage myopathy and organic aciduria compatible with multiple acylcoenzyme A (acyl-CoA) dehydrogenase deficiency. In muscle mitochondria, activities of both short-chain acyl-CoA dehydrogenase (SCAD) and medium-chain acyl-CoA dehydrogenase (MCAD) were 35% of normal. Antibodies against purified SCAD, MCAD, and electron-transfer flavoprotein were used for detection of cross-reacting material (CRM) in the patient's mitochondria. Western blot analysis showed absence of SCAD-CRM, reduced amounts of MCAD-CRM, and normal amounts of electron-transfer flavoprotein-CRM. The patient, who was unresponsive to treatment with oral carnitine, improved dramatically with daily administration of 100 mg oral riboflavin. Increase in muscle bulk and strength and resolution of the organic aciduria were associated with normalization of SCAD activity and "reappearance" of SCAD-CRM. In contrast, both MCAD activity and MCAD-CRM remained lower than normal. These results suggest that in some patients with multiple acyl-CoA dehydrogenase deficiency riboflavin supplementation may be effective in restoring the activity of SCAD, and possibly of other mitochondrial flavin-dependent enzymes.

Acyl-CoA Dehydrogenases↗
PubMed1989

Debrancher deficiency neuromuscular disorder with pseudohypertrophy in two brothers.

A neuromuscular disorder is reported in two brothers, aged 28 and 38 years, with glycogenosis type III. Both patients had proximal weakness, pseudohypertrophy of sternocleidomastoid, trapezius and quadriceps muscles, mild distal wasting and myopathic EMG changes. Pseudohypertrophy was more evident in the younger brother, whereas weakness was prominent in the older one. In the former, muscle biopsy revealed vacuolar myopathy and virtual absence of amylo-1,6-glucosidase enzyme. Few familial cases of debrancher deficiency neuromuscular disorder have been reported. Distal wasting has been considered a quite characteristic manifestation of the disease. It is also suggested that this particular kind of pseudohypertrophy may represent a distinctive feature of glycogenosis type III.

Adult↗
PubMed1989

[Muscle weakness and intolerance to exercise in mitochondrial myopathies].

Muscle weakness and intolerance to exercise are two of the main features commonly shown by patients affected by mitochondrial myopathies. In order to obtain an objective and quantitative evaluation of muscle weakness and endurance, we studied an evaluation protocol devoted to the assessment of 1) muscle strength by the isokinetic ergometer and 2) the metabolic aspects of exercise by means of Maximal Oxygen Consumption and endurance by a Steady State Submaximal exercise evaluation. The protocol has been applied to the study of patients affected by mitochondrial diseases and proved to be a reliable method to quantitate the defect in the oxidation pathways, either before or during the therapeutic follow-up.

Humans↗
PubMed1988

Hepatic and muscular presentations of carnitine palmitoyl transferase deficiency: two distinct entities.

Human carnitine palmitoyl transferase (CTP) deficiency results in two different clinical variants, one with "hepatic" and one with "muscular" symptoms. We studied CPT activity and long-chain fatty acid oxidation in fibroblast cell lines from four patients, two from each group. Overall CPT activity was deficient in patients' fibroblasts with the hepatic presentation, as previously demonstrated in patients' fibroblasts with the muscular presentation. The hepatic patients' fibroblasts displayed a CPT1 deficiency which resulted in impaired long-chain fatty acid oxidation. In contrast, CPT1 activity and palmitate oxidation were normal in muscular patients' fibroblasts. In these latter patients, the mutation presumably involved CPT2 activity. These data suggest that CPT deficiency is due to at least two different mutations, resulting in two distinct patterns of clinical and biochemical abnormalities.

Acyltransferases↗
PubMed1987

Recessive carnitine palmityl transferase deficiency: biochemical studies in tissue cultures and platelets.

In a new case of carnitine palmityl transferase (CPT) deficiency the defect was documented in muscle and muscle cultures with an isotope exchange reaction, using different concentrations of palmityl-DL-carnitine and a forward reaction with and without albumin. The defect was expressed in cultured skin fibroblasts only by the "reverse" and "hydroxamate" reactions. The parents and the patient's daughter had intermediate levels of the enzyme in platelets and fibroblasts, supporting the concept that CPT deficiency has an autosomal recessive pattern of inheritance. The growth pattern and development of muscle cultures in this CPT-deficient patient indicate that CPT activity may be sufficient to allow normal muscle differentiation in culture without lipid storage.

Acyltransferases↗
PubMed1987

Needle biopsy for muscle diagnosis and research: an Italian experience.

We report our experience of needle biopsy over the past two and a half, viz. 395 cases. We find that the technique meets the needs of diagnosis and research very satisfactorily. We describe its advantages over open biopsy and recommend it in preference to the latter, provided that the necessary technical skill for processing the sample is available.

Adolescent↗
PubMed1986

Myoadenylate deaminase deficiency in twins with recessive olivopontocerebellar atrophy.

Two adult non-identical twins with autosomal recessive olivopontocerebellar degeneration (OPCA) had markedly deficient adenylate deaminase in skeletal muscle homogenates. Ischemic exercise failed to increase the blood ammonia, while lactate increased normally. Glutamate dehydrogenase and NADP-dependent malic enzyme activities in muscle mitochondria of both patients were normal. The significance of adenylate deaminase deficiency in these twins with OPCA is discussed.

AMP Deaminase↗
PubMed1986

Systemic carnitine deficiency due to lack of electron transfer flavoprotein:ubiquinone oxidoreductase.

A child with myopathy and systemic carnitine deficiency died at age 8 years in an acute metabolic attack. He had glutaric aciduria type II, and his cultured fibroblasts contained normal activity of four different acyl CoA dehydrogenases, but there was deficiency of electron transfer flavoprotein:ubiquinone oxidoreductase (ETF-QO). This enzyme is thought to reduce coenzyme Q in the respiratory chain, funneling reducing equivalents from seven flavoproteins in the beta-oxidation of acyl CoAs. There was massive urinary excretion of the short-chain acylcarnitines that accumulated in mitochondria as a result of the ETF-QO defect. Carnitine therefore acts as a buffer for excessive accumulation of intramitochondrial acyl CoAs, and defective beta-oxidation can cause carnitine insufficiency.

Acetylcarnitine↗
PubMed1984

Propionylcarnitine excretion in propionic and methylmalonic acidurias: a cause of carnitine deficiency.

Two patients with propionic acidemia (PA) and two patients with methylmalonic aciduria (MMA) had low plasma free carnitine and increased short-chain acylcarnitines. Urinary excretion of free carnitine was decreased, while the excretion of short-chain acylcarnitines, mostly propionylcarnitine , was increased. Carnitine supplementation markedly increased the short-chain acylcarnitine fractions of both plasma and urine. Total carnitine content was decreased in skeletal muscle biopsies obtained from two of the patients. It is suggested that in these organic acidurias mitochondrial propionylcarnitine , formed from free carnitine and excess propionylCoA exchanges with free cytosolic carnitine: propionylcarnitine is then lost in the urine, causing secondary carnitine deficiency in the tissues.

Carnitine↗
PubMed1984

Systemic carnitine deficiency: clinical, biochemical, and morphological cure with L-carnitine.

A 20-year-old woman had systemic carnitine deficiency. Biochemical studies of cultured fibroblasts, skeletal muscle mitochondria, and fluids showed no evidence of other disease that might deplete tissue carnitine stores. Carnitine supplementation produced a dramatic improvement in her clinical condition: she gained weight and strength and recovered brain function, which had deteriorated slightly after repeated episodes of encephalopathy. Lipid droplets disappeared from skeletal muscle and plasma, and muscle carnitine content rose from low to normal values. On treatment, she excreted less carnitine than controls. This form of systemic carnitine deficiency may be due to defective carnitine biosynthesis.

Acids↗
PubMed1981

Systemic carnitine deficiency with peripheral nerve involvement morphological and biochemical study.

The patient, a 31-year-old woman, suffered from a weakness of the proximal muscles which subsequently worsened involving the spinal and neck muscles. During the hospitalization, the patient displayed a "burning feet" syndrome. Lab tests showed a moderate increase in CPK, Aldolase, SGPT, SGOT, lactic and pyruvic acids. Needle EMG was interpreted as "myopathic" but a marked reduction of sensitive action potentials was also detected. Muscle biopsy showed neutral lipid accumulation in muscle fibers, many small angular fibers, probably denervated ones were also evident. A liver biopsy showed fatty accumulation in hepatocytes. Free carnitine was extremely reduced in muscle and liver and just below normal level in plasma while there was a tenfold elevation of long-chain carnitine esters in plasma too. The mechanism by which carnitine deficiency can cause both neural and muscular alterations and in particular the role of carnitine in glucose metabolism is discussed.

Adult↗
PubMed1981

Heterogeneity of carnitine-palmitoyltransferase deficiency.

Episodes with muscle ache, rhabdomyolysis and myoglobinuria with or without associated renal insufficiency are characteristic of muscle carnitinepalmitoyltransferase (CPT) deficiency. However, patients differ from each other in many aspects, such as the kind of stimulus that triggers rhabdomyolysis, the ability to produce ketone bodies when fasting, whether the enzyme defect is localized in skeletal muscle or is general, and the nature of the enzyme defect, which may be in CPT I or CPT II or both. Studies of muscle, liver and fibroblasts from a patient with recurrent rhabdomyolysis spontaneously occurring or triggered by exercise or fever, revealed a CPT deficiency in the muscle and liver biopsy samples but normal CPT activity in cultured cells, differing from previously reported patients. The enzyme defect in muscle was evidenced by two different methods, but not when determined with a method that measures the formation of palmitoylcarnitine. The enzyme abnormality in the patient's liver was associated with a delayed ketone body production and with a dramatic increase in long-chain acylcarnitines in the serum when fasting. Moreover the patient was unable to build up ketones when fed long-chain triglycerides (LCT) but showed prompt ketogenic response when fed medium-chain triglycerides (MCT). The heterogeneity of clinical presentations and of the biochemical findings in patients with CPT deficiency are discussed.

Acute Kidney Injury↗