Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction

A patient with a deficiency of dihydrolipoyl dehydrogenase and neurological disease is described. The patients was placed on a branched-chain amino acid-restricted regimen. After the introduction of the regimen, there were some biochemical improvements and he achieved some developmental milestones, in contrast to previously reported patients whose neurological disease was progressive. Restriction of the branched-chain amino acids is worth trying among therapeutic measures for this disease, although restriction of the amino acids alone may not totally prevent progression of neurological disease.     

Die α-Amylase-Aktivität im Harn gesunder Schulkinder

Zusammenfassung Durch die Einführung der Mikro- und Ultramikromethode von Street u. Close zur Bestimmung der -Amylase-Aktivität in die klinischen Laboratorien wurde die Überarbeitung der bisherigen Normalwerte dieses Enzyms in den einzelnen Altersklassen und Körperflüssigkeiten erforderlich.In dieser Studie wurden 210 Schulkinder im Alter zwischen 6 und 12 Jahren auf ihre -Amylase-Ausscheidung im Harn untersucht. Der Test wurde unter Standardbedingungen an einer Greifswalder Oberschule mit einer dreistündigen Sammelperiode zwischen 7.45 Uhr und 10.45 Uhr durchgeführt. Wie schon in früheren Untersuchungen konnte auch an diesem Probandengut ein altersbezogener Anstieg der -Amylase-Aktivität und der Gesamtausscheidung der -Amylase mit dem Harn in der Zeiteinheit innerhalb zweier Altersklassen festgestellt werden. Geschlechtsgebundene Differenzen wurden nicht gefunden.Der Normalbereich der -Amylase-Aktivität im Harn für Schulkinder im Alter zwischen 6 und 12 Jahren wurde zwischen 40 und 250 SCE pro 100 ml Harn und die Gesamtausscheidung innerhalb von 3 Std mit 25-200 SCE bestimmt. Es besteht eine Korrelation zwischen der -Amylase-Ausscheidung mit dem Harn und dem spezifischen Gewicht des Harns. Die eigenen Befunde werden mit neueren Angaben der Literatur verglichen und interpretiert.

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The -amylase activity in the urine of healthy school children

Summary The introduction of new laboratory methods requires a review of the normal values. The micro- and ultra micro method for the determination of -amylase activity by Street and Close, already used successfully by many laboratories, allows the determination of enzyme activity in many biological fluids but calls for a re-assessment of the so-called normal values. In this study the results of determinations done on 210 school children are presented. The tests were perfomed with urine samples from a three hour period, collected under standard conditions. An exact statement of the quantity of -amylase excreted with the urine per unit of time was thus made possible.The 210 children belonged to two age-groups: either 7–8 or 11–12 years old. The three parameters determined from the three hour sample were: Quantity, specific weight, and -amylase activity. We were able to confirm our own earlier findings that the enzyme activity increases with age, in both, activity and quantity. Significant sex-dependent differences were not observed. The normal range of values of -amylase concentration in urine was found to be between 40 and 250 SCU (Street-Close Units) per 100 ml urine and the total excretion within three hours ranged from 25-200 SCU. A correlation between -amylase concentration and specific weight of the urine was not observed. This form of test implies an improvement of the diagnostic possibilities.

     

α-aminoadipic aciduria and persistence of fetal haemoglobin in an oligophrenic child

The case of a mentally retarded girl with a number of dysmorphic features, Raynaud's phenomenon, hypotonia and petit mal seizures is presented. Laboratory investigations showed -aminoadipic aciduria and a high level of fetal haemoglobin. Oral l-lysine loading resulted in a marked increase of -aminoadipic acid in blood and urine. After 3 months of pyridoxine medication the increase of -aminoadipic acid in blood and urine during the oral l-lysine loading test was less than in the test before treatment. A normal degradation rate of dl--amino [1-¹⁴C] adipic acid in fibroblasts of the patient, as measured by ¹⁴CO₂ production, did not indicate a primary enzyme defect in the -aminoadipic acid transamination or decarboxylation steps.The persistent HbF could be the result of stress on the erythropoiesis by a secondary induced defect in an early stage of haemoglobin synthesis in which -amino--ketoadipic acid, a structural analogue of -aminoadipic acid, is an intermediate.     

Phaeochromocytoma without symptoms: desensitization of the α- and β-adrenoceptors

A 16-year-old boy is described who had a relapse of a phaeochromocytoma 6 years after an initially successful tumour resection. The relapse was suspected after routine testing of urinary catecholamine excretion and was confirmed by scintigraphy with ¹²³I-meta-iodobenzylguanidine, computed tomography and magnetic resonance imaging. The plasma norepinephrine level was 3082 pg/ml (normal <500 pg/ml); the plasma epinephrine level was in the normal range. Surprisingly, our patient had no symptoms, including hypertension. The density of the - and -adrenoceptors on circulating blood cells was decreased. Postoperatively the plasma catecholamine levels were in the normal range. Three months after surgery the adrenoceptor density was almost normal. We conclude that the absence of clinical symptoms was probably due to desensitization of the adrenoceptors. After a successful operation to treat phaeochromocytoma, long-term monitoring of catecholamines is necessary to rule out an asymptomatic relapse.     

“Fast isoamylases” in the parotid saliva of children with cystic fibrosis and heterozygous carriers

On electrophoresis, parotid saliva always exhibits a basic pattern of 6 isoamylases. Additional faster migrating isoamylases occur in varying numbers. These fast isoamylases are generated, at least in part, by deamidation. Compared with juvenile and adult controls, a significantly greater number of fast isoamylases was found in the parotid saliva of children with cystic fibrosis and their healthy heterozygous parents. A shift in the equilibrium between amidation and deamidation is discussed in terms of its possible connection with the metabolic defect responsible for cystic fibrosis.This paper is part of the M.D. thesis submitted by H. Lubahn to the Medical Faculty of the University of Göttingen (1977)     

The clinical phenotype of β and δβ thalassemias in Greece

Based on precise evaluation of hematological findings and clinical manifestations, the relationship between genotype and clinical phenotype was studied in 475 Greek patients with and thalassemias. Almost all known genotypes are included in this series, but the most frequent was homozygous ^th high A₂ (71.6%), ^th/^th silent (7.4%), ^th/^oth high F (6.3%) and ^th/^th Dutch (6.3%).In general, the phenotype was related to the genotype, though clinical heterogeneity was detected among patients with the same genotype. The severe type of thalassemia major was most commonly found in homozygous ^th patients mainly of ^o/^o and ^o/⁺ genotypes while homozygous ⁺ patients had milder clinical manifestation. Furthermore a small group of patients, characterized as homozygous ⁺⁺ (HbF<30%) had mild thalassemia intermedia. In addition mild thalassemia intermedia was principally related with homozygous ^oth, and compound heterozygous ^th/^th silent I, and less frequently with other genotypes such as compound heterozygous with ^th/^th Dutch, ^th/^th silent II, ^th/^th high F or Lepore.It was shown that precise genetic characterization and clinical evaluation is of primary importance in predicting the prognosis and formulating the proper treatment for the individual patient with thalassemia.     

Sanfilippo type C disease: Clinical findings in four patients with a new variant of mucopolysaccharidosis III

A new genetic variant of the Sanfilippo syndrome due to deficiency of acetyl CoA: alpha-glucosaminide N-acetyltransferase, was recently demonstrated in four patients. The clinical findings of these patients are reported here. Differential diagnosis from other types of the Sanfilippo syndrome on clinical and routine laboratory criteria is difficult and enzyme assay is necessary to reach the diagnosis. Since two of the patients reported are females and consanguinity was present in one case, autosomal recessive inheritance is most probable.     

The unreliability of mean corpuscular volume and mean cellular hemoglobin determinations in the diagnosis of α-thalassemia in newborn infants

Mean corpuscular volume (MCV) and mean cellular hemoglobin (MCH) were determined by means of a Hemalog 8/90 electronic counter in 51 full-term newborn infants with -thalassemia-2 and 15 with -thalassemia-1, as well as in 150 normal newborn infants. The mean MCV and MCH values were 92 fl±06 and 33.26 pg±2.22 in the normal newborn infants, 82 fl±07 and 29.40 pg±2.60 in the -thalassemia-2 subjects, and 73 fl±06 and 26.07 pg±2.05 in the -thalassemia-1 subjects. Four of the 150 normal newborn infants had MCV's<79 fl and MCH's<29.00 pg whereas 5 of the -thalassemic subjects had MCV's>90 fl and MCH's>32.00 pg. We conclude that MCV and MCH determinations are unreliable in the diagnosis of -thalassemia in the neonatal period.     

Treatment of an aggressive haemangiomatous lesion with alpha-interferon

We report an infant who presented with an aggressive haemangiomatous lesion of the right thigh that was treated successfully with -interferon.     

Congenital tracheo-oesophageal fistula

At the Royal Children's Hospital, Melbourne, 28 patients with a congenital tracheo-oesophageal fistula were seen during a 38-year period, representing 5.2% of all babies seen with oesophageal atresia and/or tracheo-oesophageal fistula. Diagnostic delay occurred frequently because of failure to appreciate the significance of the clinical picture. There was variation in the level of the fistula; the basic pattern of investigation and management is now quite uniform.Offprint request to: N. A. Myers     

“Milky” urine—a child with chyluria

A 10-year-old boy with chyluria due to a congenital fistulous communication between the lymphatic system and the bladder is described. Chyluria can be parasitic or non-parasitic. Many causes of non-parasitic chyluria have been reported. Lymphography is the pre-operative imaging procedure of choice since it demonstrates the site, the calibre and the number of the fistulous communications. Lymphoscintigraphy shows very well the site of the fistula but is not as precise as lymphography. However, it has the advantage to be less invasive and is an excellent alternative in the non-surgical cases. The prognosis of non-parasitic chyluria is usually very good and the treatment is mostly conservative.     

Effects of immunoglobulin and gamma-interferon on the production of tumour necrosis factor-α and interleukin-1β by peripheral blood monocytes in the acute phase of Kawasaki disease

Abstract In order to study the in vitro effects of intact immunoglobulin (Ig) and gamma-interferon (INF-) in patients with Kawasaki disease, the production of tumour necrosis factor- (TNF-) and interleukin-1 (IL-1) was measured in peripheral blood monocytes (PBM) both before and after intravenous immunoglobulin (IVIG) therapy. Spontaneous production of TNF- and IL-1 both before and after IVIG therapy was significantly higher than in healthy controls. Intact Ig enhanced in vitro the production of TNF- and IL-1 both before and after IVIG therapy approximately 3–4 times as compared to the spontaneous production. INF- did not affect the production of the two cytokines. Ig enhanced IL-1 mRNA expression in PBM of KD by 3–8 times more than that of spontaneous production.Conclusion These results suggest that: (1) the mechanism of action of IVIG therapy in KD is not to cut down the production of inflammatory cytokines such as TNF- and IL-1 andf that (2) the changes of these cytokine levels may be related to the clinical effectiveness of high dose IVIG.     

Über den Einfluß einer Glucocorticosteroidapplikation auf die Aktivität der α-Amylase im Serum

Zusammenfassung Im Rahmen von Studien über den Einfluß einer Glucocorticosteroidapplikation auf die -Amylase-Aktivität in verschiedenen Körperflüssigkeiten wurden als Feldversuch vor der Durchführung von Bestimmungen an klinischem Krankengut fünf Kaninchen auf die Einwirkung von i.v. applizierten Prednisolongaben auf die -Amylase-Aktivität im Serum unter verschiedenen Versuchsbedingungen untersucht. Dabei ergab sich, daß bereits eine einmalige Gabe des Hormons zu einer deutlichen Steigerung der Enzymaktivität führt. Eine über längere Zeit durchgeführte Prednisolonbelastung provoziert -Amylase-Werte, wie sie sonst nur bei akuten Pankreatitiden gefunden werden. Die erhöhten Werte klingen in einem solchen Fall nur sehr langsam ab. Die pathogenetischen Mechanismen beim Zustandekommen dieser Veränderungen am Pankreas werden an Hand der neueren Literatur diskutiert.

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The influence of glucocorticosteroid application on the activity of -amylase in the serumI. Experiments in rabbits

Summary Glucocorticosteroids are used in the treatment of a large number of serious diseases in childhood. The doses used are often high and the period of application extends over a long time. As the influence of glucocorticosteroids on the function of the pancreas in childhood is not yet known sufficiently, we decided to follow up the changes in -amylase activity in the serum as an indicator of the excretory function of the pancreas. Five rabbits were used in the experiment and the conditions were varied. These experiments were designed as a preliminary study prior to clinical investigations.Even a single application of glucocorticosteroids leads to a significant increase of enzymic activity. Continuous applications of higher doses of prednisolone causes values of -amylase activity similar to those observed in acute pancreatitis. In such a case the enzyme activity decreases very slowly after the application of the hormone has ceased.The pathogenic mechanism of the changes in the pancreas are discussed in view of recent publications.

     

Results of the smooth-muscle fold-over double-plasty (SMFD)

Since 1980, when we developed substitute for the internal anal sphicter, the smooth-muscle fold-over double-plasty (SMFD-plasty), we have operated on seven children using this method, usually in combination with the pull-through procedure, and on five children after one or more previous operations. Since 1983, 11 cases with previous operations have undergone the modified door-wing SMFD-plasty. The results are excellent if the operation is used in primary combination with the pull-through procedure or if the door-wing modification is combined with reconstruction of the pelvic floor. It is also necessary that all cases undergo a biofeedback conditioning program.Presented at the British Association of Paediatric Surgery, XXII Annual International Congress, 17–19 July 1985, Vienna Offprint requests to: S. Hofmann-v. Kap-herr at the above address     

The γ-chain heterogeneity of haemoglobin F in German infants

-chain heterogeneity of haemoglobin F was studied in German full-term and preterm infants up to 12 months old. The AT-gene frequency calculated was about 19%. In most cases with AI-/AT-chain heterogeneity AI-chains predominated over AT-chains. There was no difference between infants with or without the AT-chain concerning haemoglobin F-concentration, F-cell percentage or G-chain percentage. The G-chains accounted for 69.2%±3.3% (SD) of the total -chains in full-term newborn infants with a decrease to 42.5%±6.5% during the first 6 months. Comparison of the G-chain decrease in preterm and in full-term newborn infants suggests a more pronounced decrease during extrauterine life than during the intrauterine course.Abbreviation Hb F haemoglobin F Dedicated to Professor E. Kleihauer on the occasion of his 60th birthday     

Kawasaki disease differs from anaphylactoid purpura and measles with regard to tumour necrosis factor-α and interleukin 6 in serum

It has been reported that tumour necrosis factor- (TNF-) is capable of inducing vascular injury, and interleukin 6 (IL-6) of inducing production of acute phase proteins and the maturation of megakaryocytes. Kawasaki disease (KD) is a systemic vasculitis with severe inflammation. We investigated whether TNF- and IL-6 activities in serum from patients with KD differs from those in anaphylactoid purpura (AP) and measles. Serum TNF- levels were measured by a sandwich enzyme immunoassay and IL-6 activities in serum were assessed by a colourimetric assay. Both KD and AP patients but not patients with measles had increased serum TNF- levels during the acute stage. With respect to IL-6, patients with KD and measles, but not AP, had increased IL-6 activities in serum during the acute stage. IL-6 activities in serum of KD patients correlated with serum C-reactive protein levels and correlated to some extent with maximum platelet counts during the course of illness. These results suggest that KD differs from AP and measles regarding both cytokines. The combination of TNF-, which may be responsible for severe vascular injury, and IL-6, which may be responsible for severe inflammation, may play an important role in acute KD.     

Ergebnisse klinischer,biochemischer, lichtmikroskopischer und ultrastruktureller Untersuchungen einer kindlichen Muskelglykogenose bei zwei Brüdern und deren schwester

Zusammenfassung Es wird über eine abortive muskuläre Form der Typ II-Glykogenose (Pompe) bei drei Geschwistern (zwei Buben und deren Schwester) berichtet.Die klinischen und routinehistologischen Befunde entsprechen dem Bild einer primär degenerativen Myopathie. Erst spezielle lichtmikroskopische (PAS-Reaktion), elektronenmikroskopische und biochemische Untersuchungen führten zur Sicherung der Diagnose.Im elektronenmikroskopischen Bild weisen die betroffenen Muskelzellen aller drei Geschwister große, autophage Vacuolen auf, die neben aggregierten Glykogengranula häufig myelinartige Abbauprodukte cytoplasmatischer Membranen enthalten. Daneben werden unspezifische Veränderungen an den übrigen Zellorganellen und den Myofibrillen beobachtet. Die biochemische Untersuchung einer Muskelbiopsie ergibt den Nachweis eines Mangels an -1,4-Glucosidase.

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Results of clinical, biochemical, Light-microscopical and ultrastructural studies of childhood glycogenosis in two brothers and their sister

Summary This report describes a mild muscular form of type II glycogenosis (Pompe) in 3 children (two boys and their sister).The clinical picture and results of routine histological tests were in keeping with the picture of a primary degenerative myopathy. It was not possible to confirm the diagnosis until special preparations were examined by light microscopy (PAS stain) and by electromicroscopical and biochemical techniques.Electron-microscopical examination of muscle cells from the affected areashowed large, autophagic vacuoles in all three sibs, which contained aggregated glycogen granules and myelin-like degradation products of cytoplasmic membranes. Nonspecific changes of the other cell organelles and the myofibrils were also observed. Biochemical examination of a muscle biopsy revealed an -1,4-glucosidase deficiency.

Wir danken Frau Prof. Dr. E. Freund-Mölbert (Lehrstuhl für Mikrobiologie, Biologie II der Universität Freiburg i. Br.) für ihre freundliche Unterstützung.     

The ageing gamete in relation to birth control failures and Down syndrome

Some indirect relationships between contraception failures and offspring with a pathological condition are reviewed, and a causal connection between them is suggested. This hypothesis is supported by the decreasing incidence of Down syndrome (DS) in general in recent years, and the increase among the younger maternal age categories as well as the effect of birth order. A more than doubled incidence of DS children among young Catholic mothers and the fact that conceptions of children with DS are preceded by unusually long periods of abstinence are emphasised and discussed. These data offer circumstantial evidence that the conceptions that occur despite application of the so called natural family planning methods in particular are at high risk. The impact of reproductive biological failures (nature) and of reproductive behaviour (nurture) on the human gametes can be disentangled by thorough studies of the epidemiology of major and minor congenital anomalies.Abbreviations DS Down syndrome - POO preovulatory over-ripeness ovopathy This paper was read at the Symposium on Pre-Conception Advice of the Nat. Assoc. of Family Planning Doctors on 29th April, 1983, Glasgow     

Emergent embolisation to control severe haematuria in Wilms’ tumour

Wilms tumour commonly presents with an abdominal mass and gross haematuria. Here, we present the novel application of paediatric renal arterial embolisation to control life-threatening haematuria in Wilms tumour.     

Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor (TNF-) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P<0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P<0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF were significantly higher in the patients with than in those without coronary aneurysm (P<0.05). These findings suggest that the serum levels of IL-6 and IL-8 obtained in the 1st week may serve as useful parameters in predicting coronary aneurysm formation in KD patients.