Second case of a successful pregnancy in maternal isovaleric acidaemia

A female patient with isovaleric acidaemia had a successful outcome from pregnancy.     

Abnormal tricarboxylic acid cycle metabolites in isovaleric acidaemia

Summary Background  Although a number of abnormal diagnostic metabolites have previously been described in the urine of patients with isovaleric acidaemia (IVA), they do not fully explain the clinical symptoms associated with this disease. Methods  On the basis of our current understanding of the TCA cycle and IVA, we predicted a number of abnormal methylated TCA cycle metabolites, initiated by methylsuccinic acid. We subsequently obtained characteristic gas chromatography–mass spectrometry elution times and mass spectra of the chemically synthesized predicted compounds and screened the urine of 6 IVA patients and 24 age-matched controls. Further proof for our findings was generated from a series of in vitro enzyme reactions using the chemically synthesized standards as substrates to their respective TCA cycle enzymes. Results  Apart from the previously described methylsuccinic and methylfumaric acid, 3-methylmalic acid, (2R,3S)- and (2R,3R)-methylcitric acid and 2-methyl-cis-aconitic acid were detected in the urine of all 6 IVA patients in increased amounts. Additionally, although not directly determined, the in vitro enzyme reaction using of 3-methylmalic acid and malate dehydrogenase, in conjunction with the detection of 2-ketobutyric acid in the urine of all 6 IVA patients, strongly suggests an additional synthesis of 3-methyloxaloacetic acid by the same cycle. Conclusion  Not only do these newly identified metabolites serve as additional diagnostic markers to those previously identified in IVA, but due to the structural arrangements of the (2R,3R)-methylcitric acid and 2-methyl-cis-aconitinic acid-derived 2-methylisocitric acid, inhibition of normal TCA cycle metabolism results at citrate synthase and isocitrate dehydrogenase, respectively. Synopsis  Methylsuccinic acid acts as the initiating substrate to a series of abnormal, potentially harmful, methylated tricarboxylic acid cycle metabolites in isovaleric acidaemia. Competing interests: None declared References to electronic databases: Isovaleric acidaemia: OMIM #243500. Isovaleryl-CoA dehydrogenase: EC 1.3.99.10.     

Improvement in exercise tolerance in isovaleric acidaemia with L-carnitine therapy

The effect of 4 weeks' treatment with oral-L-carnitine (100 mg/kg per day) on carnitine status and metabolic parameters during an incremental ramp exercise test in a 12-year-old girl with isovaleric acidaemia was examined to determine its possible therapeutic role. The maximum work rate achieved increased from 110 to 120 watts; oxygen consumption at anaerobic threshold from 600 to 800 L/min; peak oxygen consumption from 1270 to 1450 L/min; and oxygen pulse, a measure of cardiac output, from 7.0 to 8.1 L/beat. These changes were associated with increases in plasma and urinary free and acyl carnitine concentrations but no change in physical activity. This observed effect of L-carnitine on exercise performance may be on cardiac or skeletal muscle function or both. We conclude that, in this single patient with isovaleric acidaemia, L-carnitine supplementation had objective benefits and further studies on more patients are warranted.     

Methylcitrate in maternal urine during a pregnancy with a fetus affected with propionic acidaemia

Summary Patients homozygous for propionic acidaemia have high levels of methylcitric acid in urine while heterozygotes have normal levels. Methylcitric acid was determined by stable isotope dilution gas chromatography-mass spectrometry in maternal urine during a pregnancy with a fetus affected with propionic acidaemia. Although the levels increased linearly between 23 and 39 weeks of gestation, the levels were not significantly elevated above normal until after 30 weeks of gestation. Thus, determination of methylcitric acid in maternal urine is not of value for early prenatal diagnosis of propionic acidaemia.     

Successful pregnancy in a woman with mut- methylmalonic acidaemia

We report on a favourable pregnancy in a woman affected by mut^– methylmalonic acidaemia. Under vitamin B₁₂ and carnitine therapy she remained symptom-free throughout pregnancy, labour, delivery and the postpartum period and gave birth to a term, healthy female newborn. At follow-up, the child shows normal somatic and neurocognitive development.     

Diagnosis of isovaleric acidaemia by tandem mass spectrometry: False positive result due to pivaloylcarnitine in a newborn screening programme

Tandem mass spectrometric analysis of acylcarnitines and amino acids has been applied in newborn screening programmes for the detection of several inborn errors of metabolism. We report a false positive result for isovaleric acidaemia in a newborn screening programme using this method. The newborn screening sample showed a very prominent signal corresponding to the mass of isovalerylcarnitine. Repeat samples (age 6 days) of blood and urine showed similar results. However, urine organic acids were normal. Acylcarnitine analysis in blood, breast milk and urine of the mother also showed a prominent signal of the same mass. Gas chromatography–mass spectrometry of the methyl esters demonstrated that the signal in the patient's urine was due to the presence of pivaloylcarnitine, which is isomeric with isovalerylcarnitine. The patient's mother was receiving an antibiotic containing a derivative of pivalic acid to treat a urinary tract infection. Follow-up samples in the patient and the mother confirmed a decrease in the levels of pivaloylcarnitine, concomitant with the discontinuation of the treatment.We conclude that pivaloylcarnitine can give a false positive result for isovaleric acidaemia in newborns whose mothers are on treatment with pivoxilsulbactam-containing antibiotics.     

Successful pregnancy in severe methylmalonic acidaemia

Methylmalonic acidaemia is an inborn error of metabolism characterized by recurrent episodes of life-threatening ketoacidosis. With improved and intensive treatment, these patients are living into adulthood, but many experience late-onset disease complications such as chronic renal failure, chronic pancreatitis and osteopenia. We report the successful delivery of a healthy baby to a 20-year-old woman with vitamin B₁₂-unresponsive methylmalonic acidaemia who has these late-onset manifestations of the disease and had plasma methylmalonic acid concentrations of 1900mol/L during the first trimester of pregnancy.     

Second Anastomotic Recurrence After Radical Left Hemicolectomy: Report of a Case

A number of patients undergoing curative colorectal resection present with local recurrences that are not resectable at the time of diagnosis. Whereas these are predominantly perianastomotic, only a few are primarily anastomotic occurring at the suture line. A 65-year-old female with Dukes B2 adenocarcinoma of the sigmoid colon after a radical left hemicolectomy had further resections with stapled anastomosis at 12 and 22 months, for primary anastomotic recurrences. She remains well 54 months after initial surgery. The recurrent cancers were histologically similar and showed no features of microsatellite instability. The microenvironment at the anastomosis and the suture material must have contributed to this unusual course.     

Inflammatory colorectal disease and pregnancy: Report of a case

A retrospective study of women in the child-bearing age with inflammatory disease of the bowel seems to suggest that these women become pregnant as often as other women in the general population. In this small study it was 100 per cent. The incidence of subjective difficulty with conception is likewise small. Patients with Crohn's disease appear to feel better in pregnancy with regard to their intestinal problems, while more than 60 per cent of the patients with ulcerative colitis appear to do poorly. The live-birth rates for both conditions in our series were approximately 80 per cent. An unusual complication in two of our patients with Crohn's disease was a postpartum, postepisiotomy rectovaginal fistula. This may indicate a possible danger of episiotomy in patients who have Crohn's disease.     

Epicardial cyst. Report of a case with successful resection

As a result of mass-screening, a 7-year-old girl was noted to have an abnormal shadow and was subsequently diagnosed as having a pericardial cyst. During surgery, we discovered that the cyst originated from the epicardium, and only its free wall was resected with the cyst left open to the pericardial cavity. The postoperative course was uneventful. This is presumed to be the first case of epicardial cyst ever reported in Japan. In diagnosing the epicardial cyst, the use of chest films, echocardiography and computed tomography assist angiography in making a differential diagnosis from intracardiac lesion. In treatment, surgical resection is advised. Even though the cyst may be asymptomatic, the possible compression on the surrounding organs and possible rupture into the pericardial cavity must be avoided.     

Case report of a successful pregnancy following thrombolysis for acute myocardial infarction

A non-smoker 24-year-old woman presented to emergency department of Carhaix (France) for evaluation of acute chest pain. She is pregnant since six weeks and has no risk factors for coronary artery disease; her initial electrocardiogram was compatible with an acute posterior myocardial infarction (AMI). After thrombolysis by tenecteplase and treatment with both aspirin and heparin, she underwent coronary and left ventricular angiography that were normal, methergine test involved no coronary spasm. The mechanism of this AMI was not very clear. Nevertheless, an infant is born in good health eight months later after a pregnancy unrolled without any problems (aspirin was stopped at seven months, beta-blocker gradually stopped during second half of pregnancy).     

Constrictive endocarditis. Report of a case with successful surgery.

An 18-year old white youth presented with severe right heart failure and was found to have an obliterated and funnel-shaped right ventricle, massive tricuspid regurgitation, and mitral regurgitation. The haemodynamic findings were those of cardiomyopathy with obliteration on the right side. He underwent surgery consisting of decortication and peeling off of a thickened right ventricular endocardium, tricuspid valve replacement, and mitral valve repair. After surgery there was pronounced haemodynamic as well as clinical improvement. The pathological picture was that of constrictive endocarditis. We recommend this method of treatment for patients with obliterate cardiomyopathy on either side of the heart.     

Constrictive endocarditis. Report of a case with successful surgery.

An 18-year old white youth presented with severe right heart failure and was found to have an obliterated and funnel-shaped right ventricle, massive tricuspid regurgitation, and mitral regurgitation. The haemodynamic findings were those of cardiomyopathy with obliteration on the right side. He underwent surgery consisting of decortication and peeling off of a thickened right ventricular endocardium, tricuspid valve replacement, and mitral valve repair. After surgery there was pronounced haemodynamic as well as clinical improvement. The pathological picture was that of constrictive endocarditis. We recommend this method of treatment for patients with obliterate cardiomyopathy on either side of the heart.