Naoto Terada

l-2-Hydroxyglutaric aciduria: two Japanese adult cases in one family

Abstract We report two adult Japanese sisters with l-2-hydroxyglutaric aciduria (acidemia), both of whom were much older (aged 57, 47 years old) than previously reported patients (from neonate to 44 years old), and who presented with differing severity. Magnetic resonance imaging revealed typical subcortical white matter lesions in both cases and showed brainstem atrophy and thickness of the calvarium in the elder sister. l-2-Hydroxyglutaric acid levels were increased in urine, plasma, and cerebrospinal fluid. These cases suggest that organic acid analysis is necessary even in elderly patients who seem to have neurodegenerative disorders.

Hematopoietic Contribution to Skeletal Muscle Regeneration in Acid α-Glucosidase Knockout Mice

Recent studies have shown that cells from bone marrow (BM) can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved remain unknown. We performed BM transplantation in acid α-glucosidase (GAA) knockout mice, a model of glycogen storage disease type II, and our observations suggested that the BM cells contribute to skeletal muscle fiber formation. Furthermore, we showed that most CD45+:Sca1+ cells have a donor character in regenerating muscle of recipient mice. Based on these findings, CD45+:Sca1+ cells were sorted from regenerating muscles. The cell number was increased with granulocyte colony-stimulating factor after cardiotoxin injury, and the cells were transplanted directly into the tibialis anterior (TA) muscles of GAA knockout mice. Sections of the TA muscles stained with anti-laminin-α2 antibody showed that the number of CD45+:Sca1+ cells contributing to muscle fiber formation and glycogen levels were decreased in transplanted muscles. Our results indicated that hematopoietic stem cells, such as CD45+:Sca1+ cells, are involved in skeletal muscle regeneration.

An arachnoid cyst in an 8-year-old boy with neurofibromatosis

Although associations of a variety of developmental abnormalities of the brain and the spinal cord with neurofibromatosis have been reported, association of a cerebral arachnoid cyst with neurofibromatosis is extremely rare. We report the second case of this association in an 8-year-old Japanese boy.

Effect of sports activity on carnitine metabolism Measurement of free carnitine, γ-butyrobetaine and acylcarnitines by tandem mass spectrometry

The effects of sports activity on carnitine metabolism were studied using mass spectrometry. Serum levels of free carnitine, acylcarnitines (acetylcarnitine, propionylcarnitine, C4-, C5- and C8-acylcarnitine) and gamma-butyrobetaine, a carnitine precursor, were determined by tandem mass spectrometry in liquid secondary ion mass ionization mode. The coefficients of variation at three different concentrations were 2.8-7.9% for gamma-butyrobetaine, and 1.2 to approximately 6.7% for free carnitine. The recoveries added to serum were 109.1% for gamma-butyrobetaine, 89.3% for free carnitine. Sports activity caused increased serum levels of gamma-butyrobetaine, acetylcarnitine, C4- and C8-acylcarnitines and decreased serum levels of free carnitine. This method requires a small amount of sample volume (20 microl of serum) and short total instrumental time for the analysis (1 h for preparation, 2 min per sample for mass spectrometric analysis). Therefore, this method can be applied to study carnitine metabolism under various conditions that affect fatty acid oxidation.

Measurement of carnitine precursors, ε-trimethyllysine and γ-butyrobetaine in human serum by tandem mass spectrometry

Methods using tandem mass spectrometry for measurement of e-trimethyllysine and γ-butyrobetaine in human serum are described. Precursor ion scan analysis of a methylated sample was applied for γ-butyrobetaine measurement. However, for e-trimethyllysine measurement, homoarginine interfered with the methylated sample during precursor ion scan analysis. To overcome this interference, the sample was propylated and acetylated prior to precursor ion scan analysis. The obtained values resembled those obtained by enzymatic or HPLC measurement. Using tandem mass spectrometry, all members of the carnitine family, free carnitine, acylcarnitines, γ-butyrobetaine, e-trimethyllysine can be analyzed in 0.1 ml of serum. Thus, the proposed method appears to be suitable for clinical application, especially in the pediatric field.

Milder childhood form of very long-chain acyl-CoA dehydrogenase deficiency in a 6-year-old Japanese boy

Abstract We investigated the clinical and biochemical characteristics of a 6-year-old Japanese boy with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. He had hypoketotic hypoglycaemia, exercise- and fasting-induced lethargy, hepatomegaly and cardiomegaly. Significant laboratory findings included elevated plasma levels of creatine phosphokinase and acyl-carnitine and a fatty liver at biopsy suggesting a diagnosis of VLCAD deficiency. Conclusion The diagnosis of very long-chain acyl-CoA dehydrogenase deficiency was supported by the results of acyl-CoA dehydrogenase activity for C8 and C16 fatty acids in skin fibroblasts from the patient. Treatment with medium chain triglycerides and l-carnitine in the diet improved his hepatomegaly and cardiomegaly.

Modulation of C16:0‐ceramide in hypertrophied immature hearts by losartan

The angiotensin type 2 receptor plays a unique role in growth inhibition in adult myocardium via modulation of ceramide synthesis. Angiotensin type 1 (AT1)‐receptor blockade results in increased angiotensin type 2 receptor activation by angiotensin II, and AT1‐receptor blockers are sometimes prescribed to children for the treatment of cardiac hypertrophy or heart failure. We investigated the changes of ceramide lipid components in hypertrophied immature rabbit hearts after chronic administration of the AT1‐receptor blocker, losartan.

Methylmalonic aciduria with pathological fracture.

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