Glutaric aciduria type III: a distinctive non-disease?

Glutaric aciduria type III is a rare metabolic abnormality leading to persistent isolated glutaric acid excretion. We report the clinical and biochemical phenotypes of three affected children. The first patient is a boy with dysmorphic features and a chromosomal deletion (monosomy 6q26-qter) in whom a persistent glutaric aciduria (500 mmol/mol creatinine, normal <10) was detected during a routine metabolic investigation. The second boy suffered from acute gastroenteritis and hyperthyroidism, when an excessively high urinary glutaric acid excretion was identified (1460 mmol/mol creatinine). The third patient is a girl with constantly elevated glutaric acid in her urine (290 mmol/mol creatinine) but no symptoms of significant disease. In all our patients, glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency), glutaric aciduria type II (multiple acyl-CoA dehydrogenation defect), and secondary forms of glutaric aciduria (for example due to intestinal infections or mitochondrial dysfunction) could be excluded. Loading with the precursor amino acid lysine in all patients as well as with pipecolic acid in the third case led to an increase in urinary glutaric acid excretion, proving the endogenous origin of glutarate. Glutaric aciduria type III (a defect reported to be caused by peroxisomal glutaryl-CoA oxidase deficiency) is our presumptive diagnosis. However, peroxisomal glutaryl-CoA oxidase is not well characterized and no reliable approach for the direct determination of this enzyme is available to us. To our knowledge, in the English language literature only a single patient with glutaric aciduria type III has been described. Our cases reported here confirm the earlier assumption that glutaric aciduria type III is not related to a distinctive phenotype. Glutaric aciduria type III appears to be a rare metabolic abnormality, presumably of peroxisomal metabolism. However, its pathophysiological impact still needs further investigation.

Dual versus triple therapy of Helicobacter pylori infection: results of a multicentre trial.

OBJECTIVE: To compare dual therapy (omeprazole and amoxicillin) with triple therapy (omeprazole, amoxicillin, and clarithromycin) in the treatment of Helicobacter pylori infection. The efficacy of 1 mg/kg/day omeprazole was randomly compared with 2 mg/kg/day. STUDY DESIGN: 252 patients (median age, 11.0 years; range, 3-18) presenting with chronic abdominal pain underwent endoscopy and a 13C-urea breath test. Gastric biopsy specimens were taken for histological examination and for the rapid urease test. Patients were treated for two weeks: group A (n = 63) received amoxicillin (50 mg/kg; maximum, 2 g/day), group B (n = 73) received amoxicillin and clarithromycin (20 mg/kg; maximum, 1 g/day). Both groups were randomly treated with either 1 or 2 mg/kg omeprazole (maximum, 80 mg/day). Diagnostic procedures were repeated four weeks after the end of treatment. RESULTS: 11 patients were excluded; 136 patients were H pylori positive (56%), 105 of whom were re-examined after treatment. Helicobacter pylori was eradicated in 52% of group A and 83% of group B. The dose of omeprazole had no influence on the eradication rate. Specificity and sensitivity of the rapid urease test were 94% and 93%, respectively. Specificity and sensitivity of the 13C-urea breath test were 93% and 95%, respectively. CONCLUSIONS: Dual therapy can no longer be recommended. Triple therapy is more effective than dual therapy in the eradication of H pylori infection. The lower dose of 1 mg/kg omeprazole was as effective as 2 mg/kg.

True fetal mosaicism of an isochromosome of the long arm of a chromosome 20: the dilemma persists.

We report the prenatal findings of mos 46,XY/46,XY,i(20q) after amniocentesis. The propositus presented with two epidermal scalp scars, retrobulbar orbital cysts, and dyssegmentation of the thoracic spine. The abnormal cell line was discovered in cells cultured from the proximal umbilical cord and--by fluorescence in situ hybridization (FISH)--in interphase nuclei from buccal epithelium and urinary sediment but not from the placenta, lymphocytes, or skin fibroblasts.

Absence of fibula and ulna with oligodactyly, contractures, right-angle bowing of femora, abnormal facial morphology, cleft lip/palate and brain malformation in two sibs: a possibly new lethal syndrome.

Absence of fibulae, and unilateral absence of ulna, associated with lateral oligodactyly, and rectangular bowing of the femora are the prominent features of a lethal syndrome studied in two children of related parents. Other malformations are cleft lip and palate and posterior midline abnormalities of the brain. One similar though not identical MCA-syndrome was reported. The literature is reviewed with respect to ulno-fibular malformations.

[Chromosome aberrations in Prader-Willi-Labhart syndrome--critical review, documented by 4 unusual cases]. / Chromosomenaberrationen bei Prader-Willi-Labhart-Syndrom--Kritische Ubersicht, dokumentiert durch vier ungewöhnliche Fälle.

Report on two males who exhibit a syndrome which reminds Prader-Willi-Labhart syndrome (PWLS) because of craniofacial dysmorphy, acromicria, hypogenitalism, obesity and mental deficiency. A supernumerary small marker chromosome was identified as duplication of the juxtameric parts of chromosome 15. In a 15 years old female and in a 4 years old unrelated male deletion of 15q1 is due to translocation with a chromosome 7 and 20 respectively subsequent to 3:1 distribution. Therefore both patients share partial monosomies of chromosome 15 but also of the other autosome involved. Various chromosomal aberrations in PWLS but mostly deletions of chromosome 15 either isolated or associated with translocation are summarized. Patients with a PWLS like syndrome and a marker chromosome consisting of juxtameric parts of chromosome 15 constitute a particular group which is delineated from PWLS but also from a large heterogeneous group of supernumerary marker chromosomes.

[Arthritis following post-traumatic pancreatitis with subsequent pseudocyst in children]. / Beitrag zur Arthritis nach posttraumatischer Pankreatitis mit nachfolgender Pseudozyste bei Kindern.

The authors report on a nine-year-old boy who presented with arthritic complaints at the wrists and joints of the feet 6 weeks after posttraumatic pancreatitis with development of a pseudocyst. These complaints subsided only after spontaneous voiding of the contents of the cyst into the abdominal cavity. The pathogenesis, diagnosis and surgical indication in posttraumatic pancreatic pseudocysts are discussed.

[Bone marrow transplantation for aplastic anaemia (author's transl)]. / Knochenmarktransplantation bei aplastischer Anämie.

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.

[Juvenile reticulosarcoma]. / Retikulosarkom beim Kind.

The prognosis of malignant lymphoma of bone in childhood has been improved. This is due to the modern chemotherapy. Pain in the bones is one of the early symptoms. If these early symptoms are not recognized, diagnosis and therapy may be delayed. The problems of classification, diagnosis and therapy are discussed, 2 case-reports with so-called reticulum cell sarcoma are given.

[T-cell-antigen positive, E-rosette negative acute lymphoblastic leukaemia (author's transl)]. / T-Zell-Antigen positive, E-Rosetten negative akute Lymphoblastenleukämie.

The lymphoblasts from 100 patients with acute lymphocytic leukaemia were investigated for the expression of receptors for sheep erythrocytes (E) and of a specific heterologous T cell antigen (T). In 17 cases, both T cell markers were expressed simultaneously on the leukaemic cells. In 13 cases only T antigens could be demonstrated on the lymphoblasts. A quantitative analysis of T antigens by immunoautoradiography revealed that the T expression of E-T+ -lymphoblasts was in general like that of E+T+-lymphocytes in the blood of normal persons, in several cases even higher. Therefore, the failure of E-rosette formation cannot be correlated to a decrease of the other T cell differentiation marker. In 7 out of 9 tested cases, a strong acid phosphatase reaction product located paranuclearly could be demonstrated. Complement-receptors were expressed in 3 of 5 cases which were also demonstrated in some cases of the E+T+-ALL group. The latter group was characterized by a T antigen expression like that of thymocytes. 4 cases of the E-T+ALL group were adults. Since the leukaemia cells of 2 cases were negative for acid phosphatase, PAS and all surface markers including cALL antigen, the T antigen can classify undifferentiated and otherwise unclassificable leukaemias. The clinical signigicance of the E-T+-ALL seems to be important since 5 out of 9 children with this type of ALL died soon after diagnosis.

[Morphological and functional studies in a case of primary (idiopathic) thrombocythaemia in childhood (author's transl)]. / Elektronenmikroskopische und Gerinnungsuntersuchungen bei einem Fall von primärer (idiopathischer) Thrombozythämie im Kindesalter.

Primary (idiopathic) thrombocythaemia is a rare disease in childhood. Haemorrhagic diathesis and splenomegaly are principal findings besides thrombocytosis. The cases of a nine year old girl with thrombocyte levels between 2.8 and 4.5 X 10(6) microliter is described. The examination in light and electron microscopy revealed various morphological abnormalities in thrombocytes and megakaryocytes. Platelet function was disturbed in various degrees. The impact of functional abnormalities on the haemorrhagic diathesis is discussed. The findings in this child were compared to those of the better characterized picture of primary and secondary thrombozytosis in adulthood. Possible pathogenic relations to myeloproliferative diseases are also discussed.

[Treatment of aplastic anemia in children by bone marrow transplantation (author's transl)]. / Behandlung der Panmyelopathie im Kindesalter durch Knochenmarktransplantation

The course of a successful bone marrow transplantation in a 8 year old boy with severe aplastic anemia is presented. The boy lives now 22 months after bone marrow transplantation with normal bone marrow function and an essentially undisturbed performance; The indication for bone marrow transplantation for severe aplastic anemia in children is discussed. Despite improved intensive supportive care (antibiotics, infectious prophylaxis, substitution of blood components) and the treatment with corticosteroids and/or androgens the mortality of sever aplastic anemia in childhood is still high. The advantages of early bone marrow transplantation in severe cases are stressed.

Bone marrow transplantation in children with aplastic anemia and acute lymphatic leukemia.

A boy with severe Aplastic Anemia (AA) and a girl with Acute Lymphoblastic Leukemia (ALL) in relapse have been grafted with marrow from HL-A identical, mixed leukocyte culture (MLC) negative siblings after appropriate immunosuppressive and antileukemic therapy. Both of them are well 7 and 2 months after transplantation respectively. Bone marrow transplantation should be considered in children with AA and ALL in relapse, if HL-A identical, MLC negative siblings are available.