1/35. liver transplantation for methylmalonic acidaemia.The outcome for children with severe forms of methylmalonic acidaemia remains poor. patients have recurrent episodes of metabolic decompensation; many have neurodevelopmental complications and the mortality is high. Long-term survivors develop chronic renal failure. Because of the poor prognosis, transplantation has been considered. In young patients with early onset disease, liver transplantation might prevent complications and, for those in end-stage renal failure, kidney transplantation could be combined with that of the liver. The results of liver transplantation in the early onset patients have generally been disappointing. In particular there appears to be a high risk of neurological complications. The optimal management of those in end-stage renal failure has not yet been determined although combined liver and kidney transplantation has been successful. CONCLUSION: The role of transplantation in methylmalonic acidaemia has yet to be established and follow up of all patients who are considered for transplantation is essential.- - - - - - - - - - ranking = 1keywords = decompensation (Clic here for more details about this article) |
2/35. Secondary respiratory chain defect in a boy with long-chain 3-hydroxyacyl-coa dehydrogenase deficiency: possible diagnostic pitfalls.We report on a boy who suffered from microcephaly, growth retardation, cardiomyopathy and hepatic dysfunction. When he had his first febrile infection at the age of 3 months he showed metabolic decompensation. Laboratory parameters and clinical features were compatible with a beta-oxidation defect or a respiratory chain disorder. Measurement of beta-oxidation enzymes showed long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency; determination of respiratory chain complex activities revealed complete absence of complex I, II, III and IV activities in skeletal muscle and reduced activities of complexes II and IV in cultured fibroblasts, with secondary dysregulation of ATP synthase. The patient was found to be homozygous for the MTP:G1528 C mutation (LCHAD-deficiency). CONCLUSION: This patient had LCHAD deficiency as his primary metabolic disorder, leading to secondary inhibition of respiratory chain enzymes by 'toxic' metabolites.- - - - - - - - - - ranking = 1keywords = decompensation (Clic here for more details about this article) |
3/35. 3-methylcrotonyl-CoA carboxylase deficiency in an infant with cardiomyopathy, in her brother with developmental delay and in their asymptomatic father.Three affected members of one family, each with a different clinical presentation of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase (MCC) deficiency are described. The index patient presented at 7 weeks of age with feeding difficulties, sweating and tachypnoea. echocardiography showed a severely dilated left ventricle with minimal contractility. MCC deficiency was suspected on the basis of elevated urinary excretion of 3-hydroxyisovalerate and 3-methylcrotonylglycine. Deficiency of MCC activity was found in lymphocytes and fibroblasts (ca. 2% of mean normal). serum carnitine was low (free 10 micromol/l). Some other possible causes of cardiomyopathy were excluded. Cardiomyopathy was not improved by carnitine therapy. The healthy father and a developmentally delayed brother also had MCC deficiency. Both also had decreased serum carnitine concentrations, but without cardiac involvement. Dilatative cardiomyopathy as predominant symptom in isolated MCC deficiency has not been described before, although severe carnitine deficiency is a common finding in MCC deficiency. It is not clear whether this is a coincidental association. CONCLUSION: In order to understand the phenotypic spectrum of this rare disorder, cardiac evaluation should be made in patients with 3-methylcrotonyl-CoA carboxylase deficiency. Biochemical and clinical investigations have also to be performed in their parents and siblings. In addition, 3-methylcrotonyl-CoA carboxylase deficiency should be included in the differential diagnosis of dilatative cardiomyopathy.- - - - - - - - - - ranking = 0.002045602739434keywords = cardiac (Clic here for more details about this article) |
4/35. Detection of neonatal carnitine palmitoyltransferase II deficiency by expanded newborn screening with tandem mass spectrometry.The introduction of tandem mass spectrometry to newborn screening has substantially expanded our ability to diagnose metabolic diseases in the newborn period. We report the first case of neonatal carnitine palmitoyltransferase deficiency II detected by expanded newborn screening with tandem mass spectrometry. The neonate presented with dysmorphic facial features, structural malformations, renal failure, seizures, and cardiac arrythmias and died on the third day of life. This experience illustrates the importance of expanded newborn screening to avoid missing a metabolic diagnosis in early infantile death.- - - - - - - - - - ranking = 0.001022801369717keywords = cardiac (Clic here for more details about this article) |
5/35. Diagnosis of very long chain acyl-dehydrogenase deficiency from an infant's newborn screening card.Very long chain fatty acid dehydrogenase (VLCAD) deficiency is a rare but treatable cause of cardiomyopathy, fatty liver, skeletal myopathy, pericardial effusions, ventricular arrhythmias, and sudden death. Unrecognized, VLCAD deficiency may be rapidly progressive and fatal, secondary to its cardiac involvement. Because early diagnosis improves outcome, we present a neonate with VLCAD deficiency in whom retrospective analysis of the newborn screening card revealed that a correct diagnosis could have been made by newborn screening using tandem mass spectrometry. Our patient demonstrated a classic neonatal course with transient hypoglycemia at birth, interpreted as culture-negative sepsis, followed by a quiescent period notable only for hypotonia and poor feeding. At 3 months, he presented with cardiorespiratory failure and pericardial effusions, requiring pericardiocentesis, tracheostomy, and prolonged mechanical ventilation. plasma free-fatty acid and acylcarnitine profiles demonstrated small but significant elevations of C14:2, C14:1, C16, and C18:1 acylcarnitine species, findings consistent with a biochemical diagnosis of VLCAD deficiency. Enteral feeds were changed to Portagen formula with marked improvement in cardiac symptoms over several weeks. To confirm the biochemical diagnosis, molecular analysis was performed by analysis of genomic dna on a blood sample of the patient. Sequencing analysis and delineation of VLCAD mutations were performed using polymerase chain reaction and genomic sequencing. The patient was heterozygous for 2 different disease-causing mutations at the VLCAD locus. The maternal mutation was a deletion of bp 842-3 in exon 8, causing a shift in the reading frame. The paternal mutation was G 1A in the consensus donor splice site after exon 1; this splice-site mutation would likely result in decreased mRNA. The likely consequence of these mutations is essentially a null phenotype. To determine whether this case could have been picked up by tandem mass spectrometry analysis at birth when the patient was asymptomatic, acylcarnitine analysis was performed on the patient's original newborn card (after obtaining parental consent, the original specimen was provided courtesy of Dr Kenneth Pass, Director, new york State Newborn Screening Program). The blood sample had been obtained at 1 week of age and stored at room temperature for 6 months and at 70 degrees C thereafter for 18 months. Electrospray tandem mass spectrometry used a LC-MS/MS API 2000 operated in ion evaporation mode with the TurboIonSpray ionization probe source. The acylcarnitine profile obtained from the patient's original newborn card was analyzed 2 years after it was obtained. In comparison with a normal control, there was a significant accumulation of long chain acylcarnitine species, with a prominent peak of tetradecenoylcarnitine (C14:1), the most characteristic metabolic marker of VLCAD deficiency. This profile would have likely been even more significant if it had been analyzed at the time of collection, yet 2 years later is sufficient to provide strong biochemical evidence of the underlying disorder. Discussion. VLCAD was first discovered in 1992, and clinical experience with VLCAD deficiency has been accumulating rapidly. Indeed, the patients originally diagnosed with long chain acyl-CoA deficiency suffer instead from VLCAD deficiency. The phenotype of VLCAD deficiency is heterogeneous, ranging from catastrophic metabolic and cardiac failure in infancy to mild hypoketotic, hypoglycemia, and exertional rhabdomyolysis in adults. This case demonstrates that VLCAD deficiency could have been detected from the patient's own neonatal heel-stick sample. Most likely, a presymptomatic diagnosis would have avoided at least part of a lengthy and intensive prediagnosis hospitalization that had an estimated cost of $400 000. Although VLCAD is relatively rare, timely and correct diagnosis leads to dramatic recovery, so that detection by newborn screening could prevent the onset of arrhythmias, heart failure, metabolic insufficiency, and death. Fatty acid oxidation defects, including VLCAD deficiency, may account for as many as 5% of sudden infant death patients. Recent instrumentation advances have made automated tandem mass spectrometry of routine neonatal heel-stick samples technically feasible. Pilot studies have demonstrated an incidence of fatty acid oxidation defects, including short chain, medium chain, and very long chain acyl-CoA dehydrogenase deficiencies, of approximately 1/12 000. As a result, cost-benefit ratios for this approach should be systematically examined.- - - - - - - - - - ranking = 0.0039509621379884keywords = cardiac, heart (Clic here for more details about this article) |
6/35. CblC/D defect combined with haemodynamically highly relevant VSD.An infant with combined methylmalonic aciduria and homocystinuria (cblC/D defect) presented with significant VSD. She underwent successful cardiac surgery at 53 days.- - - - - - - - - - ranking = 0.001022801369717keywords = cardiac (Clic here for more details about this article) |
7/35. Echocardiographic features in a patient with primary oxalosis.Primary oxalosis is a rare congenital disorder of oxalate metabolism characterized by deposits of calcium oxalate in several organs, including the heart. We present the case of a 38-year-old man with primary oxalosis who had unique echocardiographic findings. Two-dimensional echocardiography revealed the sparkling high intensity echocardiographic pattern and concentric thickening of myocardial walls. Microscopic examinations showed the extensive deposits of calcium oxalate crystals in the myocardium. Therefore, we suggest that primary oxalosis should be given important consideration in the differential diagnosis of a hypertrophied myocardium with high intensity echocardiograms.- - - - - - - - - - ranking = 0.00088255802883742keywords = heart (Clic here for more details about this article) |
8/35. Perioperative management of a child with very-long-chain acyl-coenzyme a dehydrogenase deficiency.Very-long-chain acyl-coenzyme a dehydrogenase deficiency is an inborn error of fatty acid metabolism. The clinical presentation of this disease in children is either a severe form with onset of symptoms in the first months of life, cardiomyopathy, metabolic acidosis, myopathy and a high mortality, or a less severe form manifesting mainly with hypoglycaemia. Perioperative fasting and (even emotional) stress can trigger metabolic decompensation through the altered metabolism of endogenous fatty acids resulting in hypoglycaemia, acute cardiac and hepatic dysfunction and rhabdomyolysis. We report the perioperative management of a 9-year-old boy suffering from the severe form of this disease who underwent circumcision. metabolism was kept stable in this child by using a glucose--electrolyte infusion throughout the perioperative period to avoid the biochemical consequences of fasting and a benzodiazepine--opioid technique combined with regional anaesthesia to minimize the stress response. Considering reports about a possible interference of propofol with fatty acid oxidation and to avoid the unnecessary administration of fatty acids, propofol should not be used in these patients.- - - - - - - - - - ranking = 1.0010228013697keywords = decompensation, cardiac (Clic here for more details about this article) |
9/35. apolipoprotein a-i deficiency with accumulated risk for CHD but no symptoms of CHD.We evaluated a 69-year-old Japanese woman with apolipoprotein (apo) A-I deficiency, high levels of low-density lipoprotein (LDL)-cholesterol, hypertension and impaired glucose tolerance. The patient had corneal opacity, but neither xanthomas, xanthelasma, nor tonsillar hypertrophy. She was not symptomatic for coronary heart disease (CHD), and had normal electrocardiograms at rest and exercise using a cycle ergometer. She had severely reduced levels of high-density lipoprotein (HDL)-cholesterol (0.10-0.18 mmol/l) and no apo A-I (<0.6 mg/dl). LDL-cholesterol and apo B as well as apo E were increased even under treatment with 10 mg pravastatin per day. Gel filtration chromatography revealed that in addition to VLDL and LDL fractions, she had apo A-II rich and apo E rich fractions, which were present in the HDL fraction separated by ultracentrifugation. A cytosine deletion was identified by genomic dna sequencing of the apo A-I gene of the patient at the third base of codon 184 in the fourth exon, which led to a frame shift mutation and early termination at codon 200. This patient is the oldest among those with apo A-I deficiency reported in the literature, and she had no symptoms of CHD despite the accumulated risk for the disease.- - - - - - - - - - ranking = 0.00088255802883742keywords = heart (Clic here for more details about this article) |
10/35. propionic acidemia: a neuropathology case report and review of prior cases.propionic acidemia is a disorder of branch-chain amino acid and odd-chain fatty acid metabolism. The clinical features typically begin shortly after birth, with rare cases presenting in young adulthood. This disorder most commonly is characterized by episodic decompensations with dehydration, lethargy, nausea, and vomiting as well as a risk for neurologic sequelae. The defect is in the propionyl-CoA carboxylase enzyme with a resultant accumulation of toxic organic acid metabolites. Neuropathologic findings in this inborn error of metabolism have not been extensively characterized but include white matter spongiosis in neonates and a variable appearance in older children. We describe the pertinent literature on the neuropathology of propionic acidemia and a case report of a 4-year-old girl who had widespread gray matter vacuolization at postmortem examination. Although a previously unreported finding in propionic acidemia, diffuse gray matter vacuolization has been described in other fatty acid metabolic disorders.- - - - - - - - - - ranking = 1keywords = decompensation (Clic here for more details about this article) |
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