Search PubMed⌕ Search

Biomedical subjects

C Jakobs

Publications and source records attributed to C Jakobs.

At least 127 records · Page 7Linked to original sources
PubMed1999

Neurone-specific enolase and N-acetyl-aspartate as potential peripheral markers of ischaemic stroke.

BACKGROUND: After stroke, brain-specific proteins (including neurone-specific enolase) leak into the blood. The question addressed in the present study was whether N-acetyl-aspartate (amino acid derivative localized in cerebral neurones) could also serve as a peripheral marker of ischaemic damage. N-acetyl-aspartate levels were determined in the blood of stroke patients and related to clinical outcome, volume of infarction and to serum neurone-specific enolase. METHODS: Blood samples from 19 patients (seven women, 12 men, mean age of 73 years, range 56-88 years) were collected during the first 4 days after stroke and analysed for neurone-specific enolase (radioimmunoassay) and/or N-acetyl-aspartate (mass spectrometry). Clinical outcome was assessed using the Glasgow Outcome Score, and volume of infarction was calculated using computerized tomography (CT). Control values of N-acetyl-aspartate, determined in six female and nine male volunteers (mean age 47.4 years; range 28-73 years) were 0.26 +/- 0.02 mumol L-1. RESULTS: The increase in serum N-acetyl-aspartate was highly significant (P < 0.0001) within the first 24 h and at 72 h after stroke and correlated (P < 0.05) with volume of infarction only in patients with a bad prognosis (Glasgow Outcome Score < 5). Serum N-acetyl-aspartate at 24 h and neurone-specific enolase at 72 h were negatively correlated, suggesting that more N-acetyl-aspartate reaches the blood when brain tissue is less irreversibly affected. CONCLUSION: Serum N-acetyl-aspartate appears to be an early peripheral marker of ischaemically affected brain neurones, and the ratio of N-acetyl-aspartate to a protein marker, such as NSE, may serve as an index of irreversibility.

Aged↗
PubMed1999

Hyperhomocysteinaemia is not related to risk of distal somatic polyneuropathy: the Hoorn Study.

OBJECTIVE: Distal somatic polyneuropathy is a major contributing factor in the pathogenesis of chronic foot infections and ulcers, and may lead to lower limb amputations. Both metabolic and vascular abnormalities may contribute to the development of impaired nerve function. We therefore assessed the association between hyperhomocysteinaemia, a risk factor for cardiovascular disease, and polyneuropathy. DESIGN, SETTING AND SUBJECTS: We studied an age-, sex- and glucose-tolerance-stratified random sample of a 50- to 75-year-old general Caucasian population in the Hoorn Study (N = 629). Any polyneuropathy (N = 95) was defined as the absence of at least two of the three following sensory modalities or reflexes of either foot: light touch sense, ankle reflex and vibration sensation. Definite polyneuropathy (N = 25) was present if, in addition, the vibration perception threshold of the right big toe was abnormal. RESULTS: The prevalence of any polyneuropathy was 12.4% (33 of 266) in subjects with normal glucose tolerance (NGT), 12.6% (21 of 167) in those with impaired glucose tolerance (IGT), and 25.3% (41 of 162) in those with type 2 diabetes. The prevalence of definite polyneuropathy was 2.6% (7 of 266) in subjects with NGT, 2.4% (4 of 167) in those with IGT and 8.7% (14 of 161) in type 2 diabetic subjects. Polyneuropathy was associated with known risk factors such as diabetes, hyperglycaemia and body height. After adjustment for age, sex, HbA1c and hypertension, the odds ratio (95% CI) for any polyneuropathy per 5 micromol L-1 (about 1 SD) serum total homocysteine increment was 1.00 (0.72-1.39). After adjustment for age and sex, it was 0.62 (0.21-1.89) for definite polyneuropathy. CONCLUSION: Although a weak relation (as judged from the confidence intervals) cannot be excluded, we conclude that hyperhomocysteinaemia is probably not related to risk of distal somatic polyneuropathy.

Aged↗
PubMed1999

Plasma homocysteine concentration predicts mortality in non-insulin-dependent diabetic patients with and without albuminuria.

BACKGROUND: A high plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease in the nondiabetic population and in nondiabetic patients with end-stage renal disease. METHODS: We prospectively evaluated the impact of tHcy concentrations on mortality in 211 white non-insulin-dependent diabetic (NIDDM) patients of less than 70 years of age at entry (61 with microalbuminuria and 44 with macroalbuminuria). They were followed for a median of 6.4 (range 0.2 to 7.1) years. RESULTS: At the end of the follow-up period, 49 of 211 (23%) patients had died, 30 (61%) from cardiovascular disease. Univariate Cox survival analysis revealed that baseline tHcy level (1 micromol/liter) was associated with an increased all-cause mortality risk of 1.11 [95% confidence interval (CI) 1.08 to 1.15, P < 0.0001], and a cardiovascular mortality risk of 1.09 (CI 1.03 to 1.16, P < 0.01). The six-year cumulative all-cause mortality hazard was 44%, 14%, and 15% in the high (tHcy >/= 8.2 micromol/liter), the middle (tHcy 6. 2-8.1 micromol/liter), and the low (tHcy </= 6.1 micromol/liter) tertile of tHcy levels, respectively (P < 0.001 high vs. middle; P < 0.001 high vs. low; and P = 0.88 middle vs. low). Cox proportional hazards regression analysis revealed significant predictors of all-cause mortality to be tHcy level (per 1 micromol/liter), relative risk 1.09 (1.03 to 1.14); pre-existing coronary heart disease (yes vs. no), relative risk 1.98 (1.09 to 3.61); log10 albumin excretion rate (AER; factor 10), relative risk 1.89 (1.31 to 2.74); and age (per 1 year), relative risk 1.08 (1.03 to 1.13). Predictors of cardiovascular mortality were pre-existing coronary heart disease, log10 AER, and age. tHcy level did not predict cardiovascular mortality independently of these risk factors. CONCLUSION: Plasma tHcy concentration is a significant predictor of mortality in NIDDM patients with or without albuminuria.

Adult↗
PubMed1999

Homocysteine and methionine metabolism in ESRD: A stable isotope study.

BACKGROUND: Hyperhomocysteinemia has a high prevalence in the end-stage renal disease (ESRD) population, which may contribute to the high cardiovascular risk in these patients. The cause of hyperhomocysteinemia in renal failure is unknown, and therapies have not been able to normalize plasma homocysteine levels. Insight into methionine-homocysteine metabolism in ESRD is therefore necessary. METHODS: Using a primed, continuous infusion of [2H3-methyl-1-13C]methionine, we measured whole body rates of methionine and homocysteine metabolism in the fasting state in four hyperhomocysteinemic hemodialysis patients and six healthy control subjects. RESULTS: Remethylation of homocysteine was significantly decreased in the hemodialysis patients: 2.6+/-0.2 (SEM) vs. 3.8+/-0.3 micromol. kg(-1)x hr(-1) in the control subjects (P = 0.03), whereas transsulfuration was not 2.5+/-0.3 vs. 3.0+/-0.1 micromol. kg(-1) x hr(-1) (P = 0.11). The transmethylation rate was proportionally and significantly lower in the ESRD patients as compared with controls: 5.2+/-0.4 vs. 6.8+/-0.3 micromol. kg(-1) x hr(-1) (P = 0.02). Methionine fluxes to and from body protein were similar. CONCLUSIONS: The conversion of homocysteine to methionine is substantially (approximately 30%) decreased in hemodialysis patients, whereas transsulfuration is not. Decreased remethylation may explain hyperhomocysteinemia in ESRD. This stable isotope technique is applicable for developing new and effective homocysteine-lowering treatment regimens in ESRD based on pathophysiological mechanisms.

Adult↗
PubMed1999

In vivo research with stable isotopes in biochemistry, nutrition and clinical medicine: an overview.

Tracers and kinetic modelling provide the opportunity to follow the movement and to quantify the metabolic fates of biological compounds in vivo. For studies in children and for repeated studies in adults, the use of stable isotopically labelled substrates are preferable and safe. Measurement of isotopic enrichment in biological molecules is highly specific and can be extremely precise. This allows the development of models of biological system dynamics in cells and organs that are otherwise inaccessible for sampling. Applications in biochemistry, nutrition and clinical medicine show the potential of stable isotopes in vivo. Methodology is of paramount importance and includes the choice of bolus studies, (primed) continuous infusions, use of multiple tracers and use of isotopomer information and intrinsic labels. There is no limit to the number and kind of compounds that can be traced. Topics include intermediate metabolism (lipids, proteins and carbohydrates) using hydrogen, carbon and nitrogen labels. In clinical medicine, 13C-breath tests are available for detection of Helicobacter pylori ([13C]urea breath test), and for assessment of a variety of gastro-intestinal and hepatic functions (e.g. [13C]octanoate and mixed [13C]triglyceride breath tests for studies of gastric emptying and fat absorption, respectively). Because theoretical, methodological, physiological and practical aspects are intertwined, in vivo research with stable isotopes demands close collaboration between the clinical researcher and the chemist responsible for the mass spectrometry.

Adult↗
PubMed1999

Haemostatic and metabolic abnormalities in women with unexplained recurrent abortion.

The objective of this study was to establish whether or not patients with unexplained recurrent abortion have an increased incidence of haemostatic or metabolic abnormalities. Fifty-two patients with a history of unexplained habitual abortion (two or more spontaneous abortions before 16 weeks' gestation) were tested for protein S, protein C and antithrombin (AT) III deficiency, activated protein C (aPC) resistance, hyperhomocysteinaemia and anticardiolipin antibodies (ACA). The control group consisted of 67 healthy women with a history of only uncomplicated pregnancies. Blood samples were taken for measuring protein S, protein C, AT III, ACA and activated protein C resistance and a methionine loading test was performed. Of the 46 patients tested for protein S deficiency, 8 (17.4%) were positive. Of the 43 patients tested, two (4.7%) were protein C deficient and none was AT III deficient. Of the 42 patients tested for ACA, eight (19.1%) had detectable antibodies. Of the 44 patients tested for aPC resistance, two (4.6%) were positive. Finally, 35 patients were tested for hyperhomocysteinaemia and six (17.1%) were positive. It was concluded that parous women with a history of unexplained recurrent abortion have an increased incidence of hyperhomocysteinaemia and a trend of increased incidence of ACA can be found.

Abortion, Habitual↗
PubMed1999

Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease.

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P=0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype.

Adult↗
PubMed1999

Dynamic changes of plasma acylcarnitine levels induced by fasting and sunflower oil challenge test in children.

The dynamic changes of plasma acylcarnitine levels in 1- to 7-y-old children during fasting and after the ingestion of sunflower oil were studied. Glucose, 3-hydroxybutyrate, acetoacetate, FFA, and individual plasma acylcarnitine levels were monitored in both conditions. Fasting experiments lasted for 20 h, and acylcarnitine concentrations were analyzed at 0, 15, and 20 h of fasting. During the fat load, acylcarnitine levels were analyzed at 0, 60, 120, and 180 min. In both tests, a generalized increase of all plasma straight-chain acylcarnitines was observed. Acetylcarnitine contributed the most to the increase of total esterified carnitine. In addition, we demonstrated that the relative increase of each individual acylcarnitine during enhanced fatty acid oxidation is tightly related to its molecular structure and chain length. Fasting as well as the fat load primarily resulted in an increase of unsaturated acylcarnitines. During fasting, C(12:1) and C(14:1) showed a relatively high increase, whereas after the fat load C(16:2) and C(14:2), metabolites of linoleic acid (66% of the fat load), were the main acylcarnitines that increased.

3-Hydroxybutyric Acid↗
PubMed1999

Phytanoyl-CoA hydroxylase from rat liver. Protein purification and cDNA cloning with implications for the subcellular localization of phytanic acid alpha-oxidation.

Phytanoyl-CoA hydroxylase (PhyH) catalyzes the conversion of phytanoyl-CoA to 2-hydroxyphytanoyl-CoA, which is the first step in the phytanic acid alpha-oxidation pathway. Recently, several studies have shown that in humans, phytanic acid alpha-oxidation is localized in peroxisomes. In rat, however, the alpha-oxidation pathway has been reported to be mitochondrial. In order to clarify this differential subcellular distribution, we have studied the rat PhyH protein. We have purified PhyH from rat liver to apparent homogeneity as judged by SDS-PAGE. Sequence analysis of two PhyH peptide fragments allowed cloning of the rat PHYH cDNA encoding a 38. 6 kDa protein. The deduced amino acid sequence revealed strong homology to human PhyH including the presence of a peroxisome targeting signal type 2 (PTS2). Heterologous expression of rat PHYH in Saccharomyces cerevisiae yielded a 38.6 kDa protein whereas the PhyH purified from rat liver had a molecular mass of 35 kDa. This indicates that PhyH is probably processed in rat by proteolytic removal of a leader sequence containing the PTS2. This type of processing has been reported in several other peroxisomal proteins that contain a PTS2. Subcellular localization studies using equilibrium density centrifugation showed that PhyH is indeed a peroxisomal protein in rat. The finding that PhyH is peroxisomal in both rat and humans provides strong evidence against the concept of a differential subcellular localization of phytanic acid alpha-oxidation in rat and human.

Amino Acid Sequence↗
PubMed1999

Analysis of pristanic acid beta-oxidation intermediates in plasma from healthy controls and patients affected with peroxisomal disorders by stable isotope dilution gas chromatography mass spectrometry.

In this paper we report the development of highly sensitive, selective, and accurate stable isotope dilution gas chromatography negative chemical ionization mass spectrometry (GC-NCI-MS) methods for quantification of peroxisomal beta-oxidation intermediates of pristanic acid in human plasma: 2,3-pristenic acid, 3-hydroxypristanic acid, and 3-ketopristanic acid. The carboxylic groups of the intermediates were converted into pentafluorobenzyl esters, whereas hydroxyl groups were acetylated and ketogroups were methoximized. Hereafter, the samples were subjected to clean-up by high performance liquid chromatography. Analyses were performed by selected monitoring of the carboxylate anions of the derivatives. Control values of all three metabolites were established (2,3-pristenic acid: 2-48 nm, 3-hydroxypristanic acid: 0.02-0.81 nm, 3-ketopristanic acid: 0.07-1.45 nm). A correlation between the concentrations of pristanic acid and its intermediates in plasma was found. The diagnostic value of the methods is illustrated by measurements of the intermediates in plasma from patients with peroxisomal disorders. It is shown that in generalized peroxisomal disorders, the absolute concentrations of 2,3-pristenic acid, 3-hydroxypristanic acid, and 3-ketopristanic acid were comparable to those in the controls, whereas relative to the pristanic acid concentrations these intermediates were significantly decreased. In bifunctional protein deficiency, elevated levels of 2,3-pristenic acid and 3-hydroxypristanic acid were found. 3-Ketopristanic acid, although within the normal range, was relatively low when compared to the high pristanic acid levels in these patients.-Verhoeven, N. M., D. S. M. Schor, E. A. Struys, E. E. W. Jansen, H. J. ten Brink, R. J. A. Wanders, and C. Jakobs. Analysis of pristanic acid beta-oxidation intermediates in plasma from healthy controls and patients affected with peroxisomal disorders by stable isotope dilution gas chromatography mass spectrometry.

Diagnosis, Differential↗
PubMed1998

Hepatocyte injury in tyrosinemia type 1 is induced by fumarylacetoacetate and is inhibited by caspase inhibitors.

Tyrosinemia type 1, caused by mutations in the fumarylacetoacetate hydrolase gene (Fah), is characterized by severe liver injury. We earlier developed a tyrosinemic mouse model with two genetic defects, Fah and 4-hydroxyphenylpyruvate dioxygenase (Hpd) deficiencies. Apoptosis of hepatocytes was induced and an acute onset of liver failure occurred after administration of homogentisic acid (HGA), the intermediate metabolite between the enzymes HPD and FAH. Cytochrome c was released from mitochondria prior to liver failure in the Fah-/- Hpd-/- double-mutant mice after the administration of HGA. In a cell-free system, the addition of fumarylacetoacetate induced the release of cytochrome c from the mitochondria. We also found that caspase inhibitors were highly effective in preventing the liver failure induced by HGA in the double-mutant mice. Therefore, fumarylacetoacetate apparently induces the release of cytochrome c, which in turn triggers activation of the caspase cascade in hepatocytes of subjects with hereditary tyrosinemia type 1.

Acetoacetates↗
PubMed1998

Involvement of microsomal fatty aldehyde dehydrogenase in the alpha-oxidation of phytanic acid.

We investigated the role of microsomal fatty aldehyde dehydrogenase (FALDH) in the conversion of pristanal into pristanic acid. Cultured skin fibroblasts from controls and patients with Sjögren-Larsson syndrome (SLS) who are genetically deficient in FALDH activity were incubated with [2,3-(3)H]phytanic acid. The release of aqueous-soluble radioactivity by the SLS cells was decreased to 25% of normal, consistent with an intact formation of pristanal but a deficiency of further oxidation. SLS cells also accumulated four-fold more radioactivity in N-alkyl-phosphatidyl ethanolamine, which arises from incorporation of free aldehyde into phosphatidyl ethanolamine. Recombinant human FALDH expressed in Chinese hamster ovary cells readily oxidized pristanal and cultured fibroblasts from SLS patients showed a severe deficiency in FALDH activity (13% of normal) when pristanal was used as substrate. Nevertheless, SLS patients did not accumulate phytanic acid in their plasma. We conclude that FALDH is involved in the oxidation of pristanal to pristanic acid and that this reaction is deficient in patients with SLS.

Aldehyde Oxidoreductases↗
PubMed1998

Determination of delta13C values of valine in protein hydrolysate by gas chromatography-combustion isotope ratio mass spectrometry.

A gas chromatographic-combustion isotope ratio mass spectrometric (GC-C-IRMS) method for the determination of [1-13C]valine enrichments in protein hydrolysates is described. Using a quick derivatization method, delta13C values of the N-methoxycarbonyl methyl ester of valine can be determined from baseline separated GC peaks. Evaluation studies with respect to precision, accuracy, linearity, reduction capacity of the CuO combustion furnace and isotope dilution as a result of derivatization, showed that our GC-C-IRMS system allows robust measurement of enrichments of [1-13C]valine in the range 0 to 1.5 MPE (S.D.+/-0.01 MPE, n=3). Therefore this method is suited to determine fractional synthetic rates (FSRs) of proteins as low as one-tenth of the FSR of human albumin, in studies using a primed, continuous (6 h) infusion with [1-13C]valine plasma enrichments of approximately 15 MPE and an hourly sampling schedule.

Carbon Isotopes↗
PubMed1998

Carnitine palmitoyltransferase II specificity towards beta-oxidation intermediates--evidence for a reverse carnitine cycle in mitochondria.

Using isolated rat liver mitochondria, in the absence or presence of malonyl-CoA (an inhibitor of carnitine palmitoyltransferase I), we have found that carnitine palmitoyltransferase II (CPT II) is active with palmitoyl-CoA as well as with its beta-oxidation intermediates. A partially purified CPT II fraction from rat liver mitochondria was shown to be able to convert 3-hydroxypalmitoyl-CoA to 3-hydroxypalmitoylcarnitine, which could be identified by fast-atom-bombardment mass spectrometry. This apparent broad specificity of CPT II was further evaluated by kinetic studies using purified CPT II. It was found that CPT II readily accepts 3-oxopalmitoyl-CoA, palmitoyl-CoA, 3-hydroxypalmitoyl-CoA and 2,3-unsaturated palmitoyl-CoA as substrates with decreasing order of affinity. The apparent Vmax values found for the first three compounds were of the same order of magnitude; the 2,3-unsaturated acyl-CoA was the poorest substrate. Kinetic studies with purified CPT II showed 3-hydroxypalmitoyl-CoA to have the lowest K0.5 value (20 +/- 6 microM) of all the CoA esters studied; the highest K0.5 value (65 +/- 17 microM) was found for the 3-oxo intermediate. These findings support the hypothesis that CPT II is involved in the export of toxic long-chain acyl-CoA esters from the mitochondria by first converting them into the corresponding carnitine esters, followed by transport out of the mitochondria and subsequently out of the cell.

Animals↗
PubMed1998

Pristanic acid beta-oxidation in peroxisomal disorders: studies in cultured human fibroblasts.

To investigate the individual steps of peroxisomal beta-oxidation, human fibroblasts from controls and patients affected by different peroxisomal disorders were incubated for 96 h with pristanic acid. Hereafter, 2,3-pristenic acid and 3-hydroxypristanic acid in the incubation medium were quantified by stable isotope dilution gas chromatography mass spectrometry (GC-MS). In control fibroblasts, both intermediates were formed and excreted into the medium in significant amounts. In cells from patients affected with different types of generalized peroxisomal disorders, the formation of both intermediates was absent or low, depending on the clinical severity of the disorder. In fibroblasts from patients affected with bifunctional protein deficiency, the concentrations of 2,3-pristenic acid and 3-hydroxypristanic acid in the medium were higher than in control cell lines.

Cell Line↗
PubMed1998

Characterization of phytanoyl-Coenzyme A hydroxylase in human liver and activity measurements in patients with peroxisomal disorders.

Phytanoyl-Coenzyme A hydroxylase is a newly recognized peroxisomal enzyme which catalyses the first step in the alpha-oxidation of phytanoyl-Coenzyme A. Since measurement of this enzyme activity in human liver homogenate is of great importance especially in relation to inherited diseases in which this enzyme activity is deficient, we have studied its characteristics in human liver. The results described in this paper show that optimal activity measurements require preformed phytanoyl-Coenzyme A plus 2-oxoglutarate, Fe2+ and ascorbate. The conditions developed can be used to determine phytanoyl-Coenzyme A hydroxylase activity in human liver homogenates which is of utmost importance not only for the diagnosis of patients, but also for the purification of the enzyme from various sources.

Enzyme Inhibitors↗
PubMed1998

Clinical approach to inherited peroxisomal disorders: a series of 27 patients.

To illustrate the clinical and biochemical heterogeneity of peroxisomal disorders, we report our experience with 27 patients seen personally between 1982 and 1997. Twenty patients presented with a phenotype corresponding either to Zellweger syndrome, neonatal adrenoleukodystrophy, or infantile Refsum disease, 3 of whom had a peroxisomal disorder due to a single enzyme defect. One patient had a mild form of rhizomelic chondrodysplasia punctata, 1 had classic Refsum disease. Finally, 5 patients presented with clinical manifestations that were either unusually mild or completely atypical, and initially did not arouse suspicion of a peroxisomal disorder. They showed multiple defects of peroxisomal functions with one or several functions remaining intact, suggesting a peroxisome biogenesis disorder. The defect in peroxisome biogenesis was further characterized by variable expression in different tissues and/or individual cells in 5 patients. Studies restricted to fibroblasts failed to identify abnormalities in this group. We demonstrate that clinical manifestations of peroxisomal disorders may be very mild or completely atypical, and therefore, peroxisomal disorders should be considered in a variety of clinical settings. Furthermore, we suggest performing extensive peroxisomal investigations in every patient suspected of suffering from a peroxisomal disorder, even when the clinical presentation is typical.

Adult↗