UNLABELLED: In patients with propionic acidaemia (PA), the increased intracellular concentration of propionyl-CoA leads to a relative abundance of odd-numbered long-chain fatty acids (OLCFAs) in body lipids. We investigated the relative amount of OLCFA in erythrocyte membrane lipids over a period of 1-8 years in five patients with early onset PA and present their clinical outcome. After extraction from erythrocyte membrane lipids and esterification, fatty acids were analysed by capillary column gas chromatography. The sum of the OLCFA 15- and 17- carbon saturated and 17-carbon monounsaturated fatty acids (C15:0, C17:0, C17:1) was calculated and expressed as a percentage of the total C14-C22 fatty acids in the sample. Three patients (pccBC-complementation group) presented with a stable clinical course and showed OLCFA values usually below 1.9% (median % +/- SD: 1.4+/-0.5, 1.6+/-0.5, 1.8+/-0.5). Two patients (pccA-complementation group) had a more severe course of the disease and showed higher medians and a broader range of OLCFA levels (2.2+/-1.2 and 2.2+/-0.8). CONCLUSION: Our study shows that odd-numbered long-chain fatty acid concentrations are increased in patients with propionic acidaemia and are higher in those with a more severe clinical course. The value of odd-numbered long-chain fatty acids in the assessment of the phenotypic severity and in the management of propionic acidaemia remains to be proven in a prospective long-term study with more patients of differing phenotype.

Amino Acid Metabolism, Inborn Errors↗

PubMedDate not supplied

Carnitine supplementation induces long-chain acylcarnitine production--studies in the VLCAD-deficient mouse.

Carnitine supplementation does not affect carnitine concentrations in tissues of wild-type and very long-chain acyl-CoA dehydrogenase-deficient mice, but results in an increase in long-chain acylcarnitine production.

Acyl-CoA Dehydrogenase, Long-Chain↗

PubMedDate not supplied

Is demyelination a feature of maple syrup urine disease?

To determine whether disturbance of myelination is a pathophysiologic feature in patients with treated maple syrup urine disease (MSUD), neurophysiologic studies were performed in 10 MSUD patients ages 4-16 years. Afferent and efferent pathways were studied by visual evoked potentials, somatosensory evoked potentials, motor evoked potentials, stance-stabilizing reflexes, and peripheral nerve conduction velocity. Magnetic resonance imaging was used to detect possible cerebral white matter abnormalities. Visual evoked potentials were normal in all patients. There was only slight prolongation of central afferent and efferent conduction times and the long latency component of the stance-stabilizing reflexes. Peripheral nerve conduction studies revealed reduced sensory nerve conduction velocity in 3 patients. The neurophysiologic findings were not consistently correlated to the neurologic outcome of the patients. Magnetic resonance imaging did not reveal major abnormalities and demonstrated bilateral periventricular high intensity periventricular signals on T2-weighted images in 4 of 10 patients. It is concluded that dysmyelination is not a major pathophysiologic feature in patients with MSUD.

Adolescent↗

PubMedDate not supplied

Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency.

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is an inborn error of folate metabolism, and is inherited as an autosomal recessive trait. MTHFR is a key enzyme in folate-dependent remethylation of homocysteine, and reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Patients with this severe enzymatic deficiency are biochemically characterised by homocystinuria and hypomethioninaemia, and may suffer from neurological abnormalities, mental retardation and premature vascular disease. Here we report the molecular basis of severe MTHFR deficiency in four unrelated families from Turkish/Greek ancestry. By use of reverse-transcriptase (RT)-PCR, subsequently followed by direct sequencing analysis, we were able to identify four novel mutations in the MTHFR gene: two missense (983A-->G; 1027T-->G) and two nonsense (1084C-->T; 1711C-->T) mutations. Furthermore, a splice variant containing a premature termination codon, was observed in one patient, probably as a secondary effect of the 1027T-->G missense mutation. The ongoing identification and characterisation of mutations in the MTHFR gene will provide further insight into the heterogeneity of the clinical phenotype in severe MTHFR deficiency.

Amino Acid Sequence↗

PubMedDate not supplied

[The intermediate form of maple syrup disease].

A severely retarded and tetraspastic child died at the age of four years upon a respiratory infection with acidosis, disturbances of serum electrolytes and lactic aciduria. Brain autopsy showed a spongy degeneration and led to suspect an inborn error of amino-acid metabolism. These findings corresponded with the results of computer-tomography and were supported by post mortem amino-acid analysis. An intermediate variant of leucinosis was detected in an younger sister at the age of five months after cerebral convulsions and opisthotonic posture. The activity of the branched chain ketoacid decarboxylase in fibroblasts was reduced to 3-4% of normal. A protein restricted diet allowed a nearly normal cerebral development and improvement of computer-tomographic results. The similarity of clinical and biochemical data in both children indicate that a maple syrup urine disease was most likely the underlying disease in the older sister. Later performed electron-microscopical examinations of the older sister indicate that spongy degeneration of the central nervous system in leucinoisis is caused by a spongy myelinopathy, which is different from the alterations found in Canavan's disease, what could be pointed out for the first time.

Amino Acids, Branched-Chain↗

PubMedDate not supplied

[Intermittent maple syrup urine disease in a 12-year-old boy: clinical aspects, diagnosis and treatment].

A variant form of maple syrup urine disease (grade II) in a twelve year old boy is reported. The clinical picture was characterized by seizure-like episodes of confusion and intermittent ataxia. The diagnosis was made by showing an increased excretion of branched-chain alpha-hydroxy acids as well as evaluated plasma concentrations of the branched-chain aminoacids and alpha-ketoacids. There was a decrease of leucine degradation in cultured fibroblasts to 5 to 6% of normal. The treatment with thiamine-hydrochlorid remained without any clinical or biochemical effect in our patient. Further neurologic symptoms during acute episodes of vomiting could be avoided by dietary protein restriction and early parenteral glucose supplementation.

Ataxia↗

PubMedDate not supplied

[Breast feeding of infants with phenylketonuria].

Five infants with phenylketonuria who received their phenylalanine primarily from breast milk were compared with five other infants with PKU who received infant formula as their primary phenylalanine source. No significant differences between both groups were observed for weight gain, the daily phenylalanine intake, and mean plasma phenylalanine concentrations. This study shows that breast feeding can be continued in young infants with their difficult to predict weight gain and daily changing phenylalanine requirements.

Bottle Feeding↗

PubMedDate not supplied

A partial form of pseudohypoaldosteronism type I without renal sodium wasting.

Multiple target organ involvement in pseudohypoaldosteronism is known but partial defects involving only a single organ system have also been described. In this report we present a girl with early symptoms and a very mild course of the disease without renal salt wasting and with normal sweat osmolality. Sodium content and the sodium/potassium ratio of stool was highly elevated. Increased plasma renin activity and aldosterone concentration as well as a reduced number of aldosterone receptors in mononuclear leucocytes confirmed the diagnosis of pseudohypoaldosteronism. Partial pseudohypoaldosteronism maybe more frequent than currently diagnosed since salt loss can be compensated by intact organ systems, but nevertheless threatens the young patient during illness. Since various degrees of clinical severity of pseudohypoaldosteronism even in the same family have been described, it seems important to identify mild cases in order to monitor younger siblings.

Female↗