bluuebunny/crossref_metadata_2025_split huggingface dataset:
X‐linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060)
Authors: Barth P. G. , Wanders R. J. A. , Vreken P. , Janssen E. A. M. , Lam J. , Baas F. 
Published: December 2002

AbstractX‐linked cardioskeletal myopathy, neutropenia and abnormal mitochondria (MIM 302060) (synonyms: Barth syndrome, 3‐methylglutaconic aciduria type II, endocardial fibroelastosis type 2) has been reported in patients and families from Europe, North America and Australia. Previous studies characterized the main components of the disease: dilated cardiomyopathy, skeletal myopathy, neutropenia, 3‐methylglutaconic aciduria and diminished statural growth. Respiratory chain impairments have been found in several studies, without pinpointing a single enzyme complex. 3‐Methylglutaconic aciduria is shared with several other disorders that affect the respiratory chain. Previous studies excluded a block in the major pathway of leucine catabolism. We performed leucine loading, accompanied by fasting, in patients and observed a significant rise of 3‐methylglutaconic acid and 3‐methylglutaric acid. Taken together with the absence of an enzymatic block in the major leucine catabolic route, the possibility remains that the increased basal excretion of 3‐methylglutaconic acid and other products of branched‐chain amino acids is the result of overload of this pathway or — more likely — mitochondrial leakage. Linkage studies have localized the gene to the Xq28 region. The associated tafazzin gene (TAZ), has been fully characterized recently, and mutations located in conserved regions have been reported. Carrier detection and prenatal diagnosis have now become possible through mutation analysis. Sequence homology of the TAZ gene to a highly conserved superclass of acyltransferases (Neuwald's hypothesis) predicts a glycerophospholipid as the missing end product. This points to the (lipid) structure of the inner mitochondrial membrane as a promising new area of research.
A non‐glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP‐B) in a novel case of metachromatic leukodystrophy (MLD)
Authors: Wrobe D. , Henseler M. , Huettler S. , Pascual Pascual S. I. , Chabas A. , Sandhoff K. 
Published: December 2002

AbstractThe lysosomal degradation of sphingolipids with short oligosaccharide chains depends on small glycosylated non‐enzymatic sphingolipid activator proteins (SAPs, saposins). Four of the five known SAPs, SAP‐A, ‐B, ‐C and ‐D, are derived by proteolytic processing from a common precursor protein (SAP‐precursor) that is encoded by a gene on chromosome 10 consisting of 15 exons and 14 introns. SAP‐B is a non‐specific glycolipid binding protein that stimulates in vitro the hydrolysis of about 20 glycolipids by different enzymes. In vivo SAP‐B stimulates in particular the degradation of sulphatides by arylsulphatase A. So far, four different point mutations have been identified on the SAP‐B domain of the SAP‐precursor gene. The mutations result in a loss of mature SAP‐B, causing the lysosomal accumulation of sulphatides and other sphingolipids, resulting in variant forms of metachromatic leukodystrophy (MLD). Here we report on a patient with SAP‐B deficiency that is caused by a new homoallelic point mutation that has been identified by mRNA and DNA analysis. A 643A>C transversion results in the exchange of asparagine 215 to histidine and eliminates the single glycosylation site of SAP‐B. Metabolic labelling experiments showed that the mutation had no effect on the intracellular transport of the encoded precursor to the acidic compartments and its maturation in the patient's cells. All four SAPs (SAP‐A to SAP‐D) were detectable by immunochemical methods. SAP‐B in the patient's cells was found to be slightly less stable than the protein in normal cells and corresponded in size to the deglycosylated form of the wild‐type SAP‐B. Feeding studies with non‐glycosylated SAP‐precursor, generating non‐glycosylated SAP‐B, showed that the loss of the carbohydrate chain reduced the intracellular activity of the protein significantly. The additional structural change of the patient's SAP‐B, caused by the change of amino acid 215 from asparagine to histidine, presumably resulted in an almost completely inactive protein.
Carnitine palmitoyltransferase I deficiency in neonate identified by dried blood spot free carnitine and acylcarnitine profile
Authors: Sim K. G. , Wiley V. , Carpenter K. , Wilcken B. 
Published: December 2002

AbstractA neonate at risk for hepatic carnitine palmitoyltransferase I (L‐CPT I) deficiency was investigated from birth. The free carnitine and acylcarnitine profile in dried whole blood filter paper samples collected at ages 1 and 4 days showed a markedly elevated concentration of free carnitine (141 and 142 μmol/L, respectively), normal concentrations of acetyl‐ and propionylcarnitine, with the near absence of all other species. The diagnosis was confirmed by in vitro fatty acid oxidation screening assays and enzyme assay in cultured skin fibroblasts. Retrospective study of the newborn whole blood sample of the index case showed a similar profile (free carnitine 181 μmol/L). The newborn population distribution of free carnitine (n=143981) showed that only three samples had free carnitine >140 μmol/L (>99.9th centile), two were from L‐CPT I‐deficient neonates and one from a baby with sepsis. While there are other conditions that can cause elevated concentrations of free carnitine, an isolated elevation of free carnitine only in an apparently healthy term neonate warrants further investigation to exclude L‐CPT I deficiency.
Novel mutations cause biotinidase deficiency in Turkish children
Authors: Pomponio R. J. , Coskun T. , Demirkol M. , Tokatli A. , Ozalp I. , Hüner G. , Baykal T. , Wolf B. 
Published: December 2002

AbstractMutation analysis was performed on DNA from 31 Turkish children with profound biotinidase deficiency who were symptomatic or ascertained by newborn screening. The 98G:del7ins3 mutation is common in clinically ascertained children in both the United States and Turkish populations, but a unique common mutation, R79C, is found only in the Turkish children identified both clinically and by newborn screening. Another frequently occurring mutation, T532M, is only observed in the Turkish newborn screening group. There are four other less frequent novel mutations identified in the Turkish population. Interestingly, the Q456H and the A171T:D444H double mutation, which are the most common mutations found in the US newborn screening population and have not been observed in symptomatic children, do occur in clinically ascertained children in the Turkish population, although the double mutation may be associated with milder and/or later‐onset symptoms.
Influence of dose and age on the response of the allopurinol test for ornithine carbamoyltransferase deficiency in control infants
Authors: Riudor E. , Arranz J. A. , Rodés M. , Rubio V. , Sentís M. , Burlina A. B. 
Published: December 2002

AbstractMeasurement of urinary orotidine and orotic acid after an oral allopurinol challenge is an important diagnostic test for ornithine carbamoyltransferase deficiency that is sometimes used in infants (<1 year of age), although there is little information on normal test results in this age group. We found higher orotidine excretion in normal infants than in older children given the test, whereas orotate excretion was similar in both groups. The increased orotidine excretion appears to be due to the use in the infants of higher allopurinol doses per kilogram of body weight than in the children. The normalized‐dose dependency of the orotidine response extends even to adult age. Thus, dose‐normalized responses should be used in the test and there is no need for careful age‐matching of the controls.
Pulmonary hypertension associated with nonketotic hyperglycinaemia
Authors: Çataltepe S. , van Marter L. J. , Kozakewich H. , Wessel D. L. , Lee P. J. , Levy H. L. 
Published: December 2002

AbstractNonketotic hyperglycinaemia (NKH) is an autosomal recessive disorder characterized by defective glycine degradation by the mitochondrial glycine cleavage system. The clinical features include lethargy, hypotonia, apnoea, seizures and severe psychomotor retardation, all attributed to the accumulation of glycine in the nervous system. Pulmonary hypertension (PHN) has not been reported in NKH. We describe four patients with NKH who had PHN in addition to the characteristic manifestations of NKH. This newly recognized association might provide additional insight into the underlying pathophysiology of PHN.
The adult and adolescent clinic for inborn errors of metabolism
Authors: Brenton D. P. 
Published: December 2002

AbstractAdolescent and adult clinics for patients with inborn metabolic errors are needed first to provide care to patients who develop distinctive problems as their different disorders impinge on education, career and family life. The selection of patients in this article illustrates the range of the problems. Fundamental research will be a shared interest with paediatricians and others, but outcomes of care and treatment in young adults and in patients in middle life must be a special concern of adult clinics. It is essential to gather that information. The best model is probably an outpatient service for all ages in a single centre with paediatricians and adult physicians contributing and sharing access to dietary and laboratory services. Such a model would be best for generating the meetings, case discussions and initiatives that contribute to a thriving and energetic unit. Clearly identified centres in each country would be an effective means of acquiring the information on the adult follow‐up of these uncommon disorders.
Glucose transporters: Structure, function and consequences of deficiency
Authors: Brown G. K. 
Published: December 2002

AbstractThere are two mechanisms for glucose transport across cell membranes. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. In all other cells, glucose transport is mediated by one or more of the members of the closely related GLUT family of glucose transporters. The pattern of expression of the GLUT transporters in different tissues is related to the different roles of glucose metabolism in different tissues. Primary defects in glucose transport all appear to be extremely rare and not all possible deficiencies have been identified. Deficiency of the secondary active sodium/glucose transporters result in glucose/galactose malabsorption or congenital renal glycosuriäGLUT1 deficiency produces a seizure disorder with low glucose concentration in cerebrospinal fluid and GLUT2 deficiency is the basis of the Fanconi–Bickel syndrome, which resembles type I glycogen storage disease.
Disorders related to peroxisomal membranes
Authors: Gärtner J. 
Published: December 2002

AbstractThe peroxisome is a ubiquitous, subcellular organelle participating in a diverse array of metabolic pathways. The peroxisomal membrane and its components play a key role in organelle assembly and functions. Disorders related to peroxisomal membranes are the peroxisome biogenesis disorders and X‐linked adrenoleukodystrophy. Identification and functional characterization of these disease genes is proceeding at rapid pace helped immeasurably by work in various yeast model systems. The ultimate goal is to elucidate how the encoded proteins interact to produce apparently normal and functioning peroxisomes. The achievement of this goal will lead to a better understanding of disease pathogenesis and hopefully open therapeutic options.
Peripheral and autonomic nervous system involvement in chronic GM2‐gangliosidosis
Authors: Salman M. S. , Clarke J. T. R. , Midroni G. , Waxman M. B. 
Published: December 2002

AbstractGM2‐gangliosidosis (McKusick 268800 and 272800) is a rare hereditary, progressive disorder of ganglioside metabolism caused by deficiency of lysosomal β‐hexosaminidase (EC 3.2.1.52) activity. It is characterized by severe central nervous system involvement. Involvement of the peripheral and autonomic nervous system has been suspected but rarely documented in published case reports in the chronic form of the disease. Four patients, aged 24–29 years, with chronic GM2‐gangliosidosis were examined prospectively for evidence of peripheral and autonomic nervous system dysfunction. All had nerve conduction studies, sympathetic skin responses and cardiac monitoring during the head tilt‐table test. Three patients had objective evidence of autonomic dysfunction with abnormal sympathetic nervous skin responses and axonal sensorimotor polyneuropathy. None of the patients had evidence of significant cardiovascular autonomic dysfunction on the head tilt‐table test. The peripheral and autonomic nervous system may be involved in patients with chronic GM2‐gangliosidosis. In some cases, this may be clinically significant. On the other hand, cardiovascular autonomic instability is apparently not a significant problem in young adult patients with the disease.
Phenylalanine supplementation improves the phenylalanine profile in tyrosinaemia
Authors: Wilson C. J. , Van Wyk K. G. , Leonard J. V. , Clayton P. T. 
Published: December 2002

AbstractTyrosinaemia types I and II are caused by enzyme deficiencies in the tyrosine catabolism pathway. Successful treatment is possible with the novel enzyme inhibitor NTBC in tyrosinaemia type I and with dietary tyrosine and phenylalanine restriction in both conditions. This is achieved with a low natural protein intake and a supplementary amino acid formula that is phenylalanine‐ and tyrosine‐free. Patients on this regimen had been noted, periodically, to have very low plasma phenylalanine concentrations (<20 μmol/L). The tyrosine and phenylalanine profiles in six patients were measured. Five of the six patients had very low concentrations of phenylalanine during the later half of the day. The response to phenylalanine supplementation was assessed and supplementing the diet with phenylalanine 30–40 mg/kg per day resulted in normal concentrations throughout the day. Possible complications of hypophenylalaninaemia and potential preventive treatment strategies are discussed. Further studies are needed to investigate the longer‐term clinical and biochemical consequences of phenylalanine supplementation.
Sensitivity and specificity of free and total glutaric acid and 3‐hydroxyglutaric acid measurements by stable‐isotope dilution assays for the diagnosis of glutaric aciduria type I
Authors: Baric I. , Wagner L. , Feyh P. , Liesert M. , Buckel W. , Hoffmann G. F. 
Published: December 2002

AbstractGlutaric aciduria type I (GA I) is a recessive disorder caused by a deficiency of glutaryl‐CoA dehydrogenase (GCDH). The biochemical hallmark of the disease is the accumulation of glutaric acid and, to a lesser degree, of 3‐hydroxyglutaric acid and glutaconic acid in body fluids and tissues. A substantial number of patients show only slightly, intermittently elevated or even normal urinary excretion of glutaric acid, which makes early diagnosis and treatment to prevent the severe neurological sequelae difficult. Furthermore, elevated urinary excretion of glutaric acid can also be found in a number of other disease states, mostly related to mitochondrial dysfunction. Stable‐isotope dilution assays were designed for both glutaric acid and 3‐hydroxyglutaric acid and their diagnostic sensitivity and specificity were evaluated. Control ranges of glutaric acid in urine were 1.1–9.7mmol/mol creatinine before and 4.1–32 after hydrolysis. The respective values of 3‐hydroxyglutaric acid were 1.4–8.0 and 2.6–11.7mmol/mol creatinine. For other body fluids, control ranges in μmol/L were: for glutaric acid 0.55–2.9 (plasma), 0.18–0.63 (cerebrospinal fluid) and 0.19–0.7 (amniotic fluid); and for 3‐hydroxyglutaric acid, 0.2–1.36 (plasma), <0.2 (cerebrospinal fluid) and 0.22–0.41 (amniotic fluid). Twenty‐five patients with GCDH deficiency were studied. Low excretors (12 patients) were defined by a urinary glutaric acid below 100mmol/mol creatinine down into the normal range, while high excretors (13 patients) had glutaric acid excretions well above this value. With and without hydrolysis there was an overlap of glutaric acid values between patients and controls. Diagnostic sensitivity and specificity of 100% could only be achieved by the quantitative determination of 3‐hydroxyglutaric acid with the newly developed stable‐isotope dilution assay, allowing an accurate diagnosis of all patients, regardless of the amount of glutaric acid excreted in urine.
Disorders related to mitochondrial membranes: Pathology of the respiratory chain and neurodegeneration
Authors: Di Donato S. 
Published: December 2002

AbstractFaulty oxidative phosphorylation (OXPHOS) is observed in a number of mitochondrial disorders, and may be associated with single or multiple defects of the five complexes of the respiratory chain. From the genetic standpoint, the respiratory chain is unique as it is formed by means of the complementation of two separate genetic systems: the nuclear genome and the mitochondrial genome. The nuclear genome encodes most of the protein subunits of the respiratory complexes and most of the mtDNA replication and expression systems, whereas the mitochondrial genome encodes only 13 OXPHOS subunits and some RNA components of the mitochondrial translation apparatus. Accordingly, mitochondrial disorders due to defects in oxidative phosphorylation include both Mendelian‐inherited and cytoplasmic‐inherited diseases. Although our knowledge of these diseases has grown at an impressive rate in the past few years, it is worth noting that, as a result of complementation in the respiratory chain of nuclear‐encoded and mitochondrially‐encoded polypeptides, it is often difficult to establish a precise relationship between genomic mutations and biochemical phenotypes, or to distinguish pathogenic mutations from polymorphic variants in gene sequences.This review deals with human diseases due to mutations of the structural components of the respiratory chain, particularly focusing on the recently identified disorders caused either by mutations in nuclear genes encoding subunits of the subcomplexes or by mutations in nuclear genes affecting the functional efficiency, homeostasis, and assembly of respiratory chain subcomplexes. To better focus on OXPHOS genotype–phenotype correlations, mutations of the mtDNA‐encoded structural genes are also discussed.
UDPgalactose epimerase in lens and fibroblasts: Activity expression in patients with cataracts and mental retardation
Authors: Shin Y. S. , Korenke G.‐C. , Huppke P. , Knerr I. , Podskarbi T. 
Published: December 2002

AbstractGalactosaemia due to UDPgalactose 4‐epimerase (GALE; EC 5.1.3.2) deficiency is known to be a relatively rare autosomal recessive disorder. Up to now it has been divided into two forms, an extremely rare generalized form with a severe clinical course and a benign peripheral form that is confined to red cells (Gitzelmann 1972; Holton et al 1981; Sardharwalla et al 1988; Segal and Berry 1995). There are, however, recent descriptions of patients with the peripheral form of GALE deficiency developing juvenile cataracts or mental retardation (Endres and Shin 1990; Schulpis et al 1993; Alano et al 1998). We report here expression of the GALE enzyme in various tissues, especially in the lens, and different clinical pictures in patients we have diagnosed during the last 5 years.
A relational perspective on PTSD in early childhood
Authors: Scheeringa Michael S. , Zeanah Charles H. 
Published: December 2002

AbstractThis paper describes the clinical and research evidence for the importance of the relational context of posttraumatic stress disorder in young children. We review 17 studies that simultaneously assessed parental and child functioning following trauma. In many studies, despite limitations, an association between undesirable parental/family variables and maladaptive child outcomes has been consistently found. We present a model of the parental/family variables as moderators and vicarious traumatic agents for symptoms in young children. Also, a Compound Model is proposed, with three distinctive patterns of the parent—child relationship that impact on posttraumatic symptomatology in young children. Implications for clinical practice and research directions are discussed.
Mutual Help Groups, Perceived Status Benefits, and Well‐Being: A Test with Adult Children of Alcoholics with Personal Substance Abuse Problems
Authors: Kingree J. B. , Thompson Martie 
Published: December 2002

AbstractA field experiment was conducted to examine the potential effects of mutual help group participation on perceived status benefits, depression, and substance use among adult children of alcoholics (ACOAs) with personal substance abuse problems. Participants were randomly assigned to attend either ACOA‐specific mutual help group meetings or substance abuse education classes during the initial month that they were enrolled in a residential treatment program for low‐income substance abusers. Analyses were based on assessments made at baseline, a 1‐month posttest, and a 6‐month follow‐up. Results indicated that participation in the mutual help group promoted perceived status benefits, which in turn led to reductions in depression and substance use. These findings have clear implications for consumers of ACOA groups and can inform research on the social psychological underpinnings of different types of mutual help groups.
Oligosaccharide excretion in adult Gaucher disease
Authors: de Jong J. G. N. , Aerts J. M. F. G. , van Weely S. , Hollak C. E. M. , van Pelt J. , van Woerkom L. M. J. , Liebrand‐van Sambeek M. L. F. , Wevers R. A. 
Published: December 2002

AbstractGaucher disease is a lysosomal storage disease characterized by storage of glucocerebroside due to lysosomal glucocerebrosidase deficiency. Increased urinary excretion of sialyloligosaccharides and mannosylglycoasparagines has been described for two patients with the infantile form of the disease, probably as a consequence of obstruction of lysosomal functioning due to the glycolipid accumulation in lysosomes. By thin‐layer chromatography, we found increased urinary oligosaccharide excretion in a series of adult non‐neuronopathic patients. Oligosaccharide patterns were comparable between patients and also with the pattern observed in infantile Gaucher disease. Composition was analysed by methanolysis and gas chromatography. Mannose and N‐acetylglucosamine are the main carbohydrates in all oligosaccharide bands. A statistically significant correlation was found between oligosaccharide excretion and the severity of the disease expressed as severity score index. Patients treated with enzyme replacement therapy showed a reduction up to 65% of the original oligosaccharide excretion after 1 year of treatment, comparable with the reduction in spleen volume.
Phenylketonuria in Italy: Distinct distribution pattern of three mutations of the phenylalanine hydroxylase gene
Authors: Guzzetta V. , Bonapace G. , Dianzani I. , Parenti G. , Lecora M. , Giannattasio S. , Concolino D. , Strisciuglio P. , Sebastio G. , Andria G. 
Published: December 2002

AbstractPhenylketonuria (PKU) is an autosomal recessive disease caused by the deficiency of a liver‐specific enzyme, phenylalanine hydroxylase (PAH). The pattern of PAH mutations in Mediterranean populations appears to be different from that observed in northern Europe and Asia. Our aim was to study the molecular basis of PKU in Campania and Calabria, two regions of southern Italy. We studied 99 unrelated alleles, detecting 75.8% of the mutations. Our results show that 57% of all the PKU alleles are caused by three different mutations: IVS10nt‐546, R261Q and L48S, which display significant differences in their relative distribution across Italy. A novel mutation, a G‐to‐T transversion at the codon 257 (G257C), was also identified. This mutation results in a Gly‐to‐Cys change in the catalytic domain of the protein.