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Background/objectives: Nutritional deficiencies are frequently observed when treating patients with inborn errors of metabolism due to an unbalanced diet. Thus far, patients with isovaleric acidemia (IVA) who adhere to a restricted protein diet have not been investigated in this respect. We hypothesize that these patients may have a polyunsaturated fatty acid (PUFA) deficiency, leading to potential clinical complications.Subjects/methods: We examined the nutritional status by reporting on potential deficiencies in PUFAs in treated IVA patients. A general clinical chemistry work-up as well as gas chromatography flame ionization detector analysis was performed to determine PUFAs in the plasma of 10 IVA patients.Results: The general clinical chemistry tests did not indicate severe hematological abnormalities or nutritional insufficiencies. We identified a significant reduction in plasma PUFA levels, especially in omega-3 (all acids, P<0.001) and omega-6 (in particular 20:3n-6 P<0.0001 and 20:4n-6 P=0.0005) fatty acids. In addition, an elevation in omega-9 fatty acids, with the exception of 20:3n-9 and C22:1n-9, was not suggestive of complete essential fatty acid deficiency but rather indicative of isolated and/or combined omega-3 and omega-6 fatty acid depletion.Conclusions: This study emphasizes the potential nutritional insufficiencies that may occur because of therapeutic intervention in IVA. [ABSTRACT FROM AUTHOR]

Hyperpipecolic acidaemia is still regarded as a peroxisomal assembly deficiency. The enzyme responsible for the accumulation of pipecolic acid is located in the peroxisomes in man. We studied the appearance and alterations of peroxisomes in liver biopsy material from three unrelated children suffering from isolated hyperpipecolic acidaemia, in which only the metabolism of pipecolic acid is disturbed, using light and electron microscopy after cytochemical staining for visualisation of peroxisomes. Morphometric results showed the presence of normal-sized to small peroxisomes, an increase in number and abnormally shaped organelles, suggesting enhancement of metabolic efficiency. In one case enlarged organelles were observed. Skin fibroblasts were studied in all patients: their peroxisomes appeared to be normal. The obvious presence of peroxisomes in isolated HPA indicates that this disorder should be classified as a single peroxisomal enzyme deficiency. [ABSTRACT FROM AUTHOR]

Unlabelled: We report on a boy who suffered from microcephaly, growth retardation, cardiomyopathy and hepatic dysfunction. When he had his first febrile infection at the age of 3 months he showed metabolic decompensation. Laboratory parameters and clinical features were compatible with a beta-oxidation defect or a respiratory chain disorder. Measurement of beta-oxidation enzymes showed long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency; determination of respiratory chain complex activities revealed complete absence of complex I, II, III and IV activities in skeletal muscle and reduced activities of complexes II and IV in cultured fibroblasts, with secondary dysregulation of ATP synthase. The patient was found to be homozygous for the MTP:G1528 C mutation (LCHAD-deficiency).Conclusion: This patient had LCHAD deficiency as his primary metabolic disorder, leading to secondary inhibition of respiratory chain enzymes by 'toxic' metabolites. [ABSTRACT FROM AUTHOR]

Unlabelled: Pyruvate dehydrogenase (PDH) complex deficiency, a common cause of congenital lactic acidosis, is mostly due to mutations in the X-linked gene coding for the E1alpha subunit of the complex. We have studied two unrelated girls presenting a static encephalopathy with spastic quadriplegia, microcephaly and seizures and in one girl, hypocalcaemia, a new finding in PDH complex deficiency. PDH deficiency was diagnosed in adolescence and both girls had low PDH complex activity in muscle but normal amounts of all subunits on Western blotting, and a normal lactate/pyruvate ratio in blood and CSF. Mutation analysis of the E1alpha gene at the cDNA or DNA level revealed an arginine to histidine substitution at amino acid position 288 (R288H) in the girl with hypocalcaemia and a 12 bp insertion, predicting a four amino acid duplication at the c-terminal end of the protein in the second girl. They both carried a normal and a mutated E1alpha gene and X-inactivation studies showed skewed patterns.Conclusion: Mutation identification in pyruvate dehydrogenase complex deficiency remains important especially for the determination of the recurrence risk and for reliable genetic counselling in couples with an affected child. [ABSTRACT FROM AUTHOR]

Unlabelled: A 2.5-year-old boy presented with acute metabolic decompensation in whom 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) lyase deficiency was diagnosed. Four days after metabolic decompensation, a stroke-like encephalopathy with tonic clonic convulsion of the left arm and leg and coma developed. Brain oedema and subsequent demarcation and atrophy were observed mainly within the supply areas of the right anterior and middle cerebral artery and to a lesser extent in various sites within the right hemisphere. Residual neurological deficits included spastic paresis of the left arm and leg. and left supranuclear facial palsy and aphasia, indicating bilateral diffuse brain affection.Conclusion: In the presented patient with HMG-CoA lyase deficiency, stroke-like encephalopathy occurred days after metabolic decompensation indicating ongoing (intracerebral) metabolic derangement. Monitoring of the intracerebral accumulation of toxic metabolites by magnetic resonance spectroscopy and of cerebral haemodynamics might be useful for a better understanding of the pathogenetic mechanisms of stroke-like encephalopathy and to identify patients at risk. [ABSTRACT FROM AUTHOR]

Objective:Insulin resistance and type 2 diabetes mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. In this study, we identified the underlying molecular processes in preadipocytes of T2DM patients, a characteristic for the development of T2DM.Design and Participants:Preadipocyte cell cultures were prepared from subcutaneous fat biopsies of seven T2DM patients (age 53±12 years; body mass index (BMI) 34±5 kg m-2) and nine control subjects (age 51±12 years; BMI 30±3 kg m-2). Microarray analysis was used to identify altered processes between the T2DM and control preadipocytes.Results:Gene expression profiling showed changed expression of transcription regulators involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were downregulated, and inflammation/apoptosis was upregulated in T2DM preadipocytes.Conclusion:Decreased expression of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage. [ABSTRACT FROM AUTHOR]

Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose oxidation is decreased by fatty acids, a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity. We show that AMP-activated protein kinase (AMPK) activation by hypoxia and AICAR treatment combined with fatty acid administration synergistically induce PDK4 expression. We provide evidence that AMPK activation modulates ligand-dependent activation of peroxisome proliferator-activated receptor. Finally, we show that this synergistic induction of PDK4 decreases cellular glucose oxidation. In conclusion, AMPK and fatty acids play a direct role in fuel selection in response to cellular energy status in order to spare glucose. [ABSTRACT FROM AUTHOR]

Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas substrate oxidation per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts. [ABSTRACT FROM AUTHOR]

Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place by α-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a general peroxisomal dysfunction or from a defect in one of the enzymes involved in α-oxidation. Research on Refsum disease, belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of α-oxidation, has extended our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human disease and the way it is produced from phytol. [ABSTRACT FROM AUTHOR]

Pex19p exhibits a broad binding specificity for peroxisomal membrane proteins (PMPs), and is essential for the formation of functional peroxisomal membranes. Pex19p orthologues contain a C-terminal CAAX motif common to prenylated proteins. In addition, Saccharomyces cerevisiae and Chinese hamster Pex19p are at least partially farnesylated in vivo. Whether farnesylation of Pex19p plays an essential or merely ancillary role in peroxisome biogenesis is currently not clear. Here, we show that (i) nonfarnesylated and farnesylated human Pex19p display a similar affinity towards a select set of PMPs, (ii) a variant of Pex19p lacking a functional farnesylation motif is able to restore peroxisome biogenesis in Pex19p-deficient cells, and (iii) peroxisome protein import is not affected in yeast and mammalian cells defective in one of the enzymes involved in the farnesylation pathway. Summarized, these observations indicate that the CAAX box-mediated processing steps of Pex19p are dispensable for peroxisome biogenesis in yeast and mammalian cells. [ABSTRACT FROM AUTHOR]

The clinical, neuroradiological, neuropathological and biochemical findings in a patient with optico-cochleo-dentate degeneration (OCDD; OMIM 258700) are presented in a severe case succumbing at the age of 4 years. The electron microscopic and biochemical data showed for the first time that OCDD may occur as the phenotypic expression of D-bifunctional protein deficiency, i.e., a peroxisomal disorder. The boy was born as the first child of healthy, consanguineous parents of Turkish origin. No other family members were affected. The main clinical symptoms consisted of muscle hypotonia (“floppy infant”), generalized epileptic fits, hypacusis, rotatory nystagmus, insufficient pupillary reactions, and mental retardation. Fibroblast cultures revealed D-bifunctional protein deficiency. Neuropathological examination displayed moderate frontoparietal and insular microgyria, and atrophy of the cerebellum. Loss of neurons was severe in the granular layer, the Purkinje cell band of the cerebellum, and rather complete in the dentate nucleus. A corresponding loss of myelinated fibers associated with characteristic periodic acid-Schiff-positive macrophages was most prominent in the white matter of the cerebellum. There was additional severe loss of myelinated fibers in the central portions of the optic nerve, reduction of the nerve fiber density in the cochlear nerve, and reduction of myelinated nerve fibers by about 80–90% in the sural nerve, which has not been studied in previous cases. At the electron microscopic level, characteristic inclusions mainly in perivascular macrophages and astrocytes were the most prominent finding. The inclusions usually showed a bilaminar structure, whereas trilaminar structures, typically seen in adrenoleukodystrophy, and multilaminar structures were less frequently seen. [ABSTRACT FROM AUTHOR]

Peroxisomes are essential subcellular organelles involved in a variety of metabolic processes. Their importance is underlined by the identification of a large group of inherited diseases in humans in which one or more of the peroxisomal functions are impaired. The yeast Saccharomyces cerevisiae has been used as a model organism to study the functions of peroxisomes. Efficient oxidation of fatty acids does not only require the participation of peroxisomal enzymes but also the active involvement of other gene products. One group of important gene products in this respect includes peroxisomal membrane proteins involved in metabolite transport. This overview discusses the various aspects of fatty acid β-oxidation in S. cerevisiae. Addressed are the various enzymes and their particular functions as well as the various transport mechanisms to take up fatty acids into peroxisomes or to export the β-oxidation products out of the peroxisome to mitochondria for full oxidation to CO2 and H2O. [ABSTRACT FROM AUTHOR]

Mitochondrial β-oxidation of long-chain fatty acids requires the concerted action of three tightly integrated membrane-bound enzymes (carnitine palmitoyltransferase I and II and carnitine/acylcarnitine translocase) that transport them into mitochondria. Neonatal onset of carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive, often lethal disorder of this transport. We describe a novel splice-site mutation in the CPTII gene, found in a Moroccan family, of which four out of five children have died from the neonatal form of CPT II deficiency. Mutation detection studies at the mRNA level in the CPT II gene implied that the affected children were homozygous for the previously reported 534T insertion followed by a 25-bp deletion (encompassing bases 534-558). Studies of genomic DNA, however, revealed all patients to be compound heterozygous for this 534Tins/del 25 mutation, and for a new g→a splice-site mutation in the splice-acceptor site of intron 2. Because of these findings, prenatal diagnosis was performed in chorionic villi of three new pregnancies. This did not reveal new compound heterozygous genotypes, and, after uneventful pregnancies, all children appeared to be healthy. The new mutation is the first splice-site mutation ever identified in CPT II deficiency. The fact that it was not discovered in the patient's cDNA makes this study another example of the incompleteness of mutation detection at the mRNA level in cases where a mutation leads to aberrant splicing or nonsense-mediated messenger decay. [ABSTRACT FROM AUTHOR]

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia, an autosomal recessive inherited defect of the urea cycle. Most patients described so far have presented with the classical form of the disease. There are also patients with a mild form of citrullinemia in whom the exact molecular basis and clinical relevance are uncertain. Mutations in the human ASS gene have not yet been described in mildly affected or asymptomatic patients with citrullinemia. The genomic sequence of the human ASS gene is not precisely known making mutation analysis difficult. Here, the entire genomic DNA sequence and mutations in the ASS gene of patients with the classical and mild form of the disease are described. The mutations c.1168G→A (G390R) and IVS13+5 G→A and the novel mutation c.323G→T (R108L) have been found to be associated with classical citrullinemia, whereas the novel mutations c.535T→G (W179R), and c.1085G→T (G362V) have been detected on alleles of the mildly affected patients. Thus, mutations found in the human ASS gene of asymptomatic children with biochemical abnormalities and in some cases enzymatically proven citrullinemia have allowed us to classify these cases as ASS-deficient patients. The elucidation of the structure of the human ASS gene has made possible the use of intronic primers for molecular analysis of patients with mild disease and the classical form, and provides another option for prenatal diagnostics in affected families with the severe type. [ABSTRACT FROM AUTHOR]

Unlabelled: Carnitine-acylcarnitine translocase deficiency is a rare and life-threatening mitochondrial fatty acid beta-oxidation disorder. We describe a patient who, despite a severe clinical course and an extremely low carnitine-acylcarnitine translocase activity, is currently alive and in good health. We performed an extensive analysis of all previously published cases in order to evaluate the clinical features and prognostic factors. Reports on 21 patients with carnitine-acylcarnitine translocase deficiency were obtained. Only 5 out of the 21 patients survived early childhood. At least 20 siblings are reported to have died of sudden unexplained death in the neonatal period. Although phenotype and residual enzyme activity have been suggested to be related to outcome, we were not able to establish such a relationship.Conclusion: Phenotype and residual enzyme activity do not appear to be major prognostic factors. Vigorous work-up in order to reach an expedite diagnosis and prompt medical intervention during acute episodes, especially in the neonatal period, may prevent fatal complications. [ABSTRACT FROM AUTHOR]

Abstract We present the clinical, pathological, biochemical, and molecular results on an infant girl with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency and data on her deceased elder brother for whom this condition was retrospectively diagnosed. Clinical signs were liver enlargement and elevated liver enzymes, failure to thrive, and neurological disease (coma, seizures) triggered by an infectious stress. In the second child hepatic failure and status epilepticus developed during the onset of a rotavirus gastroenteritis. A barbituric coma was induced, but hypotonia and lack of eye pursuit persisted after suppression of antiepileptic drugs. She ultimately died of heart failure. Unlike previously reported cases, both of these patients had early-onset cirrhosis, and severe neurological disease was observed in the second child. Conclusion Liver cirrhosis and brain damage may be underestimated in cases of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency and may occur early in life. [ABSTRACT FROM AUTHOR]

Unlabelled: We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis, and subsequently, a fasting test revealed severe metabolic ketoacidosis with normal blood glucose after 13 h which suggest a defect in ketolysis. In his cultured skin fibroblasts succinyl-CoA:acetoacetate transferase was deficient (residual activity 15%). Treatment in the acute phase consisted of sodium bicarbonate. At the present age of 9 years, psychomotor and physical development are within normal limits.Conclusion: Defects of ketolysis probably are underdiagnosed disorders and should be considered in infants and young children with persistent ketosis. [ABSTRACT FROM AUTHOR]

Unlabelled: Rhizomelic chondrodysplasia punctata (RCDP) is clinically characterized by symmetrical shortening of the proximal limbs, contractures of joints, a characteristic dysmorphic face, and cataracts. In the classical form an impairment of several peroxisomal functions and enzymes (plasmalogen synthesis, phytanic acid oxidation, 3-oxoacyl-CoA thiolase) has been repeatedly shown. Recently a variant involving only the peroxisomal dihydroxyacetonephosphate acyltransferase (DHAP-AT) has been described. We present a patient with isolated DHAP-AT deficiency and all clinical, radiological and pathological features of classical RCDP. For the first time, microscopy and immunocytochemistry of hepatocytes could be performed.Conclusion: In contrast to studies on classical rhizomelic chondrodysplasia punctata which have shown enlarged peroxisomes in numbers varying from hepatocyte to hepatocyte, the peroxisomes in our patient seem to be normal in size, number and shape. [ABSTRACT FROM AUTHOR]

3-Hydroxyacyl-CoA dehydrogenase deficiency is a newly recognised fatty acid oxidation disorder with a usually fatal outcome. We present a further patient who presented with hypoketotic hypoglycaemia, hepatopathy, secondary carnitine deficiency and increased plasma long-chain acylcarnitines. 3-Hydroxydicarboxylic aciduria was present and the diagnosis confirmed in cultured skin fibroblasts. Our patient is compared with those reported in the literature with respect to clinical symptoms, differential diagnosis and possible therapeutic regimens. [ABSTRACT FROM AUTHOR]

We describe a 16-year-old boy suffering from psychomotor retardation, sensorineuronal hearing impairment, peripheral neuropathy, hepatosplenomegaly, short stature and delayed puberty. Postnatally, muscular hypotonia, mild facial dysmorphism and delayed fontanelle closure had been noticed. At the time of our examination, adrenal cortical function was normal. Biochemical analysis revealed accumulation of very long (> C22) chain fatty acids in plasma and fibroblasts. Furthermore, elevated levels of intermediates of bile acid synthesis and phytanic acid were detectable. These findings are consistent with a defect in the peroxisomal beta-oxidation system. A generalised defect of peroxisomal function was excluded by normal plasmalogen levels in erythrocytes and normal plasmalogen de novo synthesis in fibroblasts. Immunoblotting of the peroxisomal beta-oxidation enzymes gave normal results suggesting retained immunoreactivity but catalytic inactivity of one of the enzymes involved, probably either the trifunctional protein or the peroxisomal ketothiolase. This case markedly differs clinically from the few published reports on isolated deficiencies of peroxisomal beta-oxidation. Among the patients with comparable biochemical findings, this is the first report of survival into adolescence. [ABSTRACT FROM AUTHOR]

Peroxisomal disorders are genetic diseases in which an impairment in one or more peroxisomal function(s) causes clinical and multiple biochemical abnormalities. Early recognition of the major peroxisomal disorders in which functional peroxisomes are virtually absent, leading to a generalised impairment of peroxisomal functions, is of utmost importance, as this will enable the prenatal diagnosis of these severe diseases in future pregnancies. Unfortunately, clinical recognition of these disorders can be difficult because of the aspecific and varying phenotypic presentation. We analysed the clinical characteristics in 40 patients suspected of having a peroxisomal disorder to identify specific clinical criteria for diagnosis. From this study we conclude that the combined presence of at least three major clinical characteristics (present in greater than 75% of the affected patients, including psychomotor retardation, hypotonia, impaired hearing, low/broad nasal bridge, abnormal ERG, hepatomegaly) and one or more minor characteristics (present in 50%-75% of the patients, like large fontanelles, shallow orbital ridges, epicanthus, anteverted nostrils, retinitis pigmentosa) warrants biochemical investigation of peroxisomal functions. Further prospective investigations will have to be done to evaluate these criteria. [ABSTRACT FROM AUTHOR]

Two siblings were found to be affected by long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one of which died suddenly and unexpectedly on the 3rd day of life suffering from extreme hypoketotic hypoglycaemia. The younger sibling started to have feeding problems, lowered consciousness, and liver dysfunction at the age of 5 months. Her urine contained large amounts of C6-C14 3-hydroxydicarboxylic acids and conjugated 3-hydroxyoctanoic acid, as verified by gas chromatography/mass spectrometry. Plasma long-chain acylcarnitine was increased. A clue to the diagnosis was given by the results of a phenylpropionic acid loading test. This revealed small, but significant amounts of conjugated 3-hydroxyphenylpropionic acid (phenylhydracrylic acid) in the patient's urine. Subsequently, the activity of long-chain 3-hydroxyacyl-CoA dehydrogenase was found to be deficient in cultured skin fibroblasts. Based on the findings obtained by a medium-chain triglyceride load, a diet enriched in this type of fat was prescribed. On this regimen the patient started to thrive, signs of cardiomyopathy disappeared, and her liver function normalized. [ABSTRACT FROM AUTHOR]

A progressive demyelinating cerebral disorder is described in a normally-appearing female infant with neonatal seizures, progressive psychomotor deterioration, deafness, retinopathy, peripheral neuropathy and loss of myelin observed on magnetic resonance imaging (MRI) scanning. MRI also showed the absence of macroscopic neocortical dysplasia which is usually found in Zellweger syndrome (ZS). Adrenal cortical function was normal. The patient died at the age of 37 months. Extensive biochemical investigations of peroxisomal functions in the patient revealed an impairment of peroxisomal beta-oxidation resulting in elevated levels of very long (greater than C22) chain fatty acids in plasma and fibroblasts. Moreover, elevated plasma levels of intermediates of bile acid biosynthesis such as tri- and dihydroxycholestanoic acid were found. Other peroxisomal functions were normal. Immunoblotting of the peroxisomal beta-oxidation enzyme proteins in liver from the patient revealed normal responses with antisera against acyl-CoA oxidase, bifunctional protein and thiolase respectively. From these data we conclude that the patient had a deficiency of a single peroxisomal beta-oxidation enzyme at the level of either the bifunctional protein or peroxisomal thiolase with retained immunoreactivity against these enzymes. [ABSTRACT FROM AUTHOR]

In recent years a number of biochemical abnormalities have been described in patients with the infantile form of Refsum disease, including the accumulation of very long chain fatty acids, trihydroxycoprostanoic acid and pipecolic acid. In this paper we show that catalase-containing particles (peroxisomes), alkyl dihydroxyacetone phosphate synthase and acyl-CoA oxidase protein are deficient in patients with infantile Refsum disease. These findings suggest that in the infantile form of Refsum disease, as in the cerebro-hepato-renal (Zellweger) syndrome the multiplicity of biochemical abnormalities is due to a deficiency of peroxisomes and hence to a generalized loss of peroxisomal functions. As a consequence the infantile form of Refsum disease can be diagnosed biochemically by methods already available for the prenatal and postnatal diagnosis of the cerebro-hepato-renal (Zellweger) syndrome. [ABSTRACT FROM AUTHOR]

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A 4.5-year-old boy received a combined liver and kidney transplant for correction of hyperoxaluria type 1. Both organs were from the same donor and functioned primarily. Three months after transplantation, urine oxalate excretion reached a maximum of 10,500 mumol/24 h and remained above 2300 mumol/24 h for the next 2 months. Two months later, oxalate excretion decreased to about 565 mumol/24 h, indicating exhaustion of a large oxalate pool. Six months after transplantation plasma oxalate is near normal (4.9 mumol/l). With the exception of one episode of acute rejection of the renal transplant, both organs were tolerated well and continue to have a unimpaired function 9 months after transplantation. However, there is increased echogenity on renal ultrasound, indicating oxalate deposits in the grafted kidney. This case illustrates that successful combined transplantation of both liver and kidney can be performed in infants, resulting in cure of the metabolic defect. The prolonged or acute excretion of oxalate may lead to oxalate deposition in the grafted kidney without impaired graft function or early graft loss. [ABSTRACT FROM AUTHOR]

In this paper we show that whereas acyl-CoA: dihydroxyacetone phosphate acyltransferase, a membrane-bound peroxisomal enzyme, is deficient in homogenates of cultured amniotic fluid cells of fetuses with Zellweger syndrome, catalase a soluble peroxisomal matrix enzyme is present in normal amounts. Digitonin titration experiments revealed a striking difference in the percentage of particle-bound catalase in control and Zellweger amniocytes: in Zellweger amniocytes all catalase activity was found to be present in the soluble cytoplasm, (less than 5% particle-bound), whereas in control amniocytes catalase was found to be predominantly particle-bound (62% +/- 8%, n = 5). Measurement of the percentage of particle-bound catalase by means of digitonin titrations thus provides a simple prenatal test for Zellweger syndrome via the direct demonstration of the presence or absence of catalase-containing particles (peroxisomes). [ABSTRACT FROM AUTHOR]