[Intravenous immunoglobulins (IVIG) in treatment of an antiphospholipid syndrome in pregnancy]. / Intravenöse Immunglobuline (IVIG) in der Behandlung eines Antiphospholipid-Syndroms in der Schwangerschaft.

A patient with a history of early onset preeclampsia and repeated fetal death, high titer IgG anticardiolopin antibodies and prolonged aPTT was treated during her third pregnancy with intravenous immunoglobulins (IVIG) from the seventh month of pregnancy onwards. Every month--after a loading dose of 30 g immunoglobulins--a daily infusion of 3 g immunoglobulin was for three days was given during six consecutive cycles. The patients pregnancy ended preterm with a life birth, delivered by cesarean section, because of a severe preeclampsia. The 1600 g weighing boy was in good health. Each treatment with IVIG resulted in a reduction of anticardiolipin-antibodies. During the seventh months observation period, a gradual increase in PAI activity/factor VIIIR:Ag was found. A partial transient reduction of antiphospholipid-antibody levels was observed immediately following each treatment course resulting in an accelerated fetal outcome.

[Prenatal diagnosis of sialidosis, a defect of the lysosomal enzyme neuraminidase]. / Pränatale Diagnostik der Sialidose, eines Defektes des lysosomalen Enzyms Neuraminidase.

Sialidosis, a lysosomal storage disease, ranged as oligosaccharidosis, is a genetic enzyme defect with a significantly restricted survival rate of the child concerned. After the preceded birth of a child who died of sialidosis, we succeeded in the correct prenatal exclusion of the disease with the prediction of a heterocygotic carrier status by biochemical analysis of cultivated amnion cells. The growth of these cells as well as the postnatal examined fibroblasts was significantly reduced. The possibility of the prenatal diagnosis of sialidosis allowed a pregnancy following the birth of a diseased child.

Childhood neuromuscular disease with rimmed vacuoles.

A 5-year-old boy suffered from a slowly progressive non-familial neuromuscular disease, clinically marked by generalised muscle weakness, atrophy and hypotonia, a "myopathic" EMG and mildly elevated CK values. His gastrocnemius muscle showed marked myopathy, type I fibre predominance, and numerous "rimmed" vacuoles. This boy's condition is regarded as a childhood neuromuscular disease with rimmed vacuoles.

The clinical spectrum of alpha-L-iduronidase deficiency.

We present five patients with alpha-L-iduronidase deficiency who do not have the typical Hurler or Scheie phenotypes; they are compared to 28 similarly atypical cases from the literature. Phenotypic differences are pointed out and intrafamilial similarities stressed. Among the various possible explanations for this situation, the existence of genetic compounds seems acceptable for some of the cases, but others seem to be caused by different mutations. The elucidation of these alternative possibilities from recent biochemical research is discussed.

N-Acetylneuraminic acid storage disease.

Increased amounts of free sialic acid were found in body fluids, leukocytes, cultured fibroblasts, and liver tissue of a four-year-old boy with mental retardation, ataxia, and clinical and radiologic findings of a mild mucopolysaccharidosis. A diagnosis of Salla disease was made though in contrast to earlier reports, recurrent upper respiratory infections and hepatosplenomegaly were present already in infancy, and skeletal abnormalities of dysostosis multiplex were found in early childhood. Free sialic acid in the urine was identified as N-acetylneuraminic acid by 1H-NMR spectroscopy. Sialidase activities were normal. Increased amounts of bound sialic acid were found in liver and cultured fibroblasts and were attributed to an intracellular inhibition of sialyloligosaccharide-degrading neuraminidase by excessive amounts of free neuraminic acid. The molecular basis of N-acetylneuraminic acid storage disease is unknown but may be related to a defective transport mechanism preventing neuraminic acid from leaving the lysosomal compartment.

Neuraminidase deficiency presenting as non-immune hydrops fetalis.

A newborn infant with oedema, ascites and hepatosplenomegaly is described. In ascites fluid foamy macrophages were found, in a liver biopsy cytoplasmic inclusions and membrane-bound vacuoles were seen. Furthermore the child excreted excessive amounts of sialic acid-rich oligosaccharides in the urine, and therefore a neurovisceral degenerative disorder was assumed. The diagnosis of sialidosis was confirmed by enzymatic assay in cultured fibroblasts, in which a complete deficiency of the lysosomal enzyme neuraminidase could be demonstrated. After recurrent septicaemias the child became dystrophic and died at the age of 6 months. Our case is compared with sialidosis observed by other authors, the wide phenotypic diversity within this biochemical defect is emphasised. The occurrence of hydrops fetalis in lysosomal storage diseases is discussed.

The value of CT in diagnosis and prognosis of different inborn neurodegenerative disorders in childhood.

Inborn errors of metabolism in 40 children have been investigated by computed tomography to obtain data on the degree of cerebral involvement in neurodegenerative and storage disorders: 20 children had various mucopolysaccharidoses, 8 sphingolipidoses , 3 mucolipidoses, 2 oligosaccharidoses , 3 ceroidlipofuscinoses and 4 had various leucodystrophies . Diagnosis in all patients except Alexander's disease was established by biochemical or histological means. The main findings on CT were cerebral atrophy with enlargement of the ventricles and the subarachnoid spaces and hypodensity of the white matter. The degree of cerebral atrophy seemed to develop according to the age of the patients, as could be seen from the patients with mucopolysaccharidosis III, metachromatic leucodystrophy and GM1-gangliosidosis. Hypodensity of the white matter was found in mucopolysaccharidosis I-H, II-B, VI, in mucolipidosis II and in patients with leucodystrophies . On the other hand, there was great variability in these CT findings even in siblings, as seen in four patients with mucopolysaccharidosis VI. Among the series there were several patients who did not show any abnormalities in CT, so that a negative CT did not exclude these disorders, even the leucodystrophies . CT features such as cerebral atrophy or hypodensity were helpful in the evaluation of these disorders, though a diagnosis could not be made by CT alone.

Cranial computed tomography in disorders of complex carbohydrate metabolism and related storage diseases.

Computed tomography (CT) was performed on 34 children with different disorders of complex carbohydrate metabolism and related storage diseases to obtain data on the degree of cerebral involvement. The main findings on CT were cerebral atrophy and hypodensity of the white matter. There was a great variability in these CT findings, even in siblings. Among the patients there were several in whom CT was normal, so a negative study does not exclude one of these disorders. These findings show that CT features such as cerebral atrophy or hypodensity are helpful in the evaluation of these disorders, though a diagnosis cannot be made on the basis of CT alone.

Liver pathology in transient neonatal hyperammonemia.

Ultrastructural investigations have been performed on two cases of transient neonatal hyperammonaemia (TNH). This newly recognized metabolic disorder is chiefly characterized by severe hyperammonaemia in the postnatal period, a comatous state, absence of abnormal organic aciduria, normal activity of urea cycle enzymes and, usually, complete recovery. The aetiology is presently unknown. Electron microscopy uncovered rather congruent alterations of hepatocyte structure, with a wide spectrum of mitochondrial lesions, an increase of autophagous bodies with organelle remnants, and changes in the excretory apparatus. Thus, in contrast to some of the hereditary disorders of the urea cycle, no specific structural changes could be found in TNH. This finding is in line with the observation of normal activities of main urea enzymes in these cases, and indicates that a different biochemical system may be pathogenetically involved in TNH.

[Phenotypes in heteroglycanoses and sphingolipidoses (author's transl)]. / Phänotyp bei Heteroglykanosen und Sphingolipidosen.

Sphingolipidoses and heteroglycanoses are inborn errors of the carbohydrate metabolism. Biochemically and clinically hetero-glycanoses are sub-divided into mucopolysaccharidoses, oligosaccharidoses and mucolipidoses. These disorders of complex carbohydrate metabolism are due to the inborn defect of one or more lysosomal enzymes which in turn cause an intracellular accumulation of not-degraded complex carbohydrates corresponding to a wide pattern of clinical expression and symptomatology ranging from psychomotor retardation without any dysmorphic signs to severe features of a storage disease with dwarfism, peculiar facial appearance, organomegaly and skeletal changes. Investigations of recent years revealed that there is tremendous phenotypic variation even within diseases caused by a deficiency of the same enzyme. On the other hand, clinically indistinguishable phenotypes may be caused by the defect of different enzymes.

Clinical and biochemical delineation of aspartyl-glycosaminuria as observed in two members of an Italian family.

Two members of a consanguineous Italian family are described with the symptoms of aspartylglycosaminuria. Both patients exhibit mental retardation, some facial dysmorphism and discrete radiological abnormalities affecting the skull and vertebrae. Peripheral blood smears revealed multivacuolated lymphocytes. Enzyme studies in leucocytes and cultured fibroblasts showed an absence of aspartylglucosaminidase activity. Urinary analysis demonstrated abnormal oligosacchariduria and aspartylglycosamine excretion. Angiokeratoma corporis diffusum was observed in one patient.

Aspartylglycosaminuria in an Italian family: clinical and biochemical characteristics.

Two members of a consanguineous Italian family are described with symptoms of aspartylglycosaminuria. Both patients exhibit mental retardation, some facial dysmorphism and discrete radiological abnormalities affecting the skull and vertebrae. Peripheral blood smears revealed multi-vacuolated lymphocytes. Enzyme studies in leukocytes showed an absence of aspartylglucosaminidase activity. Urine analysis demonstrated abnormal oligosacchariduria. Angiokeratoma corporis diffusum was observed in one patient. The disease is seen as not being limited to Scandinavia or to patients of Scandinavian descent.

Urinary oligosaccharide screening in patients with beta-galactosidase deficiency.

Following ion-exchange chromatography and subsequent thin-layer chromatography, 3 peculiar oligosaccharide excretion patterns were distinguished in 3 patients with beta-galactosidase deficiency. Each patient differed clinically and it is proposed that this method may be of use in characterizing various forms of beta-galactosidase deficiency.

Comprehensive urinary screening for inborn errors of complex carbohydrate metabolism.

A rapid and comprehensive urinary screening programme is presented by which most of the "heteroglycanoses" can be identified. The diagnoses obtained on a total of 44 patients with different storage disorders shows the usefulness of the method.

Mucopolysaccharidosis II (Hunter disease) with corneal opacities. Report on two patients at the extremes of a wide clinical spectrum.

Clinically visible corneal opacities were observed in a patient with an extremely severe form of mucopolysaccharidosis II. In a second patient with an unusually mild form of mucopolysaccharidosis II, discrete corneal opacities were detected by slit-lamp examination. Thus clear corneae can no longer be regarded as a hallmark of mucopolysaccharidosis II.

Increased urinary excretion of keratan sulfate in fucosidosis.

In two children exhibiting the clinical symptoms of fucosidosis, the diagnosis was biochemically ascertained by the demonstration of a profound altpha-L-fucosidase deficiency in cultured skin fibroblasts. The non-dialysed urines of these fucosidosis patients were separated into two fractions by chromatography on Biogel P-2. The first fraction containing the glycosaminoglycans was further fractionated on Dowex 1 X 2 by stepwise elution with increasing NaCl concentrations. Keratan sulfate-chondroitin sulfates attached to the same peptide core were assayed and characterised mainly in the fractions eluted with 1.25, 1.5, 2.0 and 3.0 mol/1 NaCl. Whereas the excretion of normal children of the same age was found to be 0.77 mumol glucosamine equivalents per day in the 2 mol/1 and 3 mol/1 NaCl fraction, the two patients excreted 6.7 (M. C.) and 3.5 (M. S.) mumol glucosamine equivalents per day, respectively. Since keratan sulfate contains alpha-fucose at the non-reducing terminal, this increase in excretion of long chain keratan sulfate in fucosidosis could result from impaired degradation of keratan sulfate, due to the alpha-fucosidase deficiency.