Clinical and molecular characteristics of two transaldolase-deficient patients.

UNLABELLED: Transaldolase (TALDO) deficiency is a rare metabolic disease in the pentose phosphate pathway, which manifests as a severe, early-onset multisystem disease. The body fluids of affected patients contain increased polyol concentrations and seven-carbon chain carbohydrates. We report the molecular and clinical findings in two recently diagnosed transaldolase-deficient children, both presented at birth. During infancy, they presented thin skin with a network of visible vessels, spider telangiectasias and multiple haemangiomas. Such unusual skin changes are characteristic of liver damage. Later, the patients developed rapidly progressive nodular liver fibrosis, tubulopathy and severe clotting disturbances. The clinical features of these patients were in line with previously studied patients with transaldolase deficiency. The diagnosis was established by detecting high concentrations of erythritol, ribitol, arabitol, sedoheptitol, perseitol, sedoheptulose and sedoheptulose-7-phosphate in the urine. Detection was made by gas chromatography and liquid chromatography-tandem mass spectrometry and then confirmed by molecular analysis of the TALDO gene. CONCLUSION: Transaldolase deficiency, a rare early-onset multisystem disease, should be considered by neonatologists, paediatricians, hepatologists and nephrologists in the differential diagnosis of patients presenting hepatosplenomegaly, thrombocytopenia, anaemia, bleeding diathesis, liver failure and tubulopathy.

[Peroxisomes--functions and disturbances in human metabolism]. / Peroksysomy--funkcje i zaburzenia metaboliczne.

Peroxisomes, classical compartments of eucaryotic cells have significant functions in cellular metabolism, which beta-oxidation fatty acids and detoxification of H2O2 are the most important biochemical process. Defects in genes encoding for peroxisomal proteins result in biochemical malfunctioning of these organelles and constitute base for severe human's inherited diseases. This article presents the most important aspects concerning peroxisomal biogenesis, biochemical functions and their disturbance.

[A newly discovered metabolic diseases due to defects in the pentose pathway]. / Nowo opisane choroby metaboliczne zwiazane z bledami metabolizmu na szlaku przemiany pentoz.

Two previously unreported inborn errors of metabolism occur in the reversible part of the pentose phosphate pathway. Deficiency of ribose-5-phosphate isomerase has been described in one patient who suffered from a progressive leukoencephalopathy and developmental delay. Transaldolase deficiency has been diagnosed in 11 patients from 6 families in which the probands presented in the newborn and antenatal period with hepatospIenomegaly, hemolytic anaemia, hepatic fibrosis, kidney problems. Enzymes deficiency results in accumulations in body fluids erythritol, arabitol, ribitol, sedoheptitol, sedoheptulose, sedoheptulose-7-phosphate. Isomerase and transaldolase activity can be determined in leukocytes or fibroblasts.

Transaldolase deficiency in two new patients with a relative mild phenotype.

Transaldolase (TALDO) deficiency is a recently described inborn error of metabolism of the pentose phosphate pathway that so far has been diagnosed in only eight patients. In this article, we report the clinical course and biochemical findings of two newly identified patients with TALDO deficiency-two sons of consanguineous parents from Polish origin, presenting with neonatal onset of bleeding diathesis, haemolytic anemia, thrombocytopenia and hepatosplenomegaly. Subsequently the patients had persistent thrombocytopenia, a bleeding tendency, impaired liver function and fibrosis. Their physical and psychomotor development progressed normally.

Clinical and neuropathological picture of familial encephalopathy with bifunctional protein deficiency.

Peroxisomal diseases are a heterogeneous group of genetic metabolic disorders which are caused by incorrect biogenesis of peroxisomes or a defect in activity of particular enzymes located in those organelles.D-bifunctional protein (D-BP) deficiency belongs to the second group of peroxisomal diseases characterised by dysfunction of a single peroxisomal enzyme. Bifunctional protein is a catalyst in the second and third stage of the beta-oxidation of fatty acids. Gene locus of bifunctional protein deficiency comprises chromosomes 5q2 and 3p23-p22. The authors present two siblings with progressing family encephalopathy. In the younger brother the diagnosis of a bifunctional protein deficiency was made. The girl died before a diagnosis was made;however, due to the presence of a very similar clinical condition a suspicion arises that the girl had a peroxisomal disease. In the siblings were ascertained characteristic dysmorphic features, delayed psychomotor development, polymorphic epileptic seizures and generalized muscular hypotonia with areflexia. The neuropathological findings were consistent in general with MRI findings showing features of hypomyelination. Also neuron heterotopias that were found in autopsy are a form of pathology typical for D-BP.

Gas chromatographic determination of D-/L-arabinitol ratio in healthy Polish children.

The D-/L-arabinitol enantiomers ratio (a marker of disseminated candidiasis of Candida species) in urine was determined by gas chromatography (GC) in 198 healthy Polish children ranging in age from 0 to 18 years. The urine samples were dry and trifluoroacetic anhydride (TFAA)-treated. Enantiomers derivatives were separated on a chiral column (beta-Dex 120, 60 m x 0.25 mm I.D.). A glass "solid-phase" injector and electron capture detector (ECD) were used. The ECD response was linear with correlation coefficients 0.999. The limit of detection was 0.02 micromol/l. Good results in terms of reproducibility, accuracy (RSD<10%, bias<6%), and linearity were obtained from real urine samples containing up to 400 micromol/l D-arabinitol. TFA-arabinitol derivatives in biological samples were stable from 1 to 5 days (depending on the arabinitol contents), while TFA-arabinitol standard derivatives were stable for 2 weeks. The identity of D- and L-arabinitol were confirmed by GC-MS analysis. The mean D-/L-arabinitol ratios ranged from 2.48 to 1.65 in the examined groups. The D-/L-arabinitol ratio was found to be exponentially regressive with age. A few cases of diagnosis of disseminated candidiasis by the GC method and confirmed by blood culture are described. The described GC method was also used for monitoring antifungal treatment of patients with disseminated candidiasis.

Monitoring of very long-chain fatty acids levels in X-linked adrenoleukodystrophy, treated with haematopoietic stem cell transplantation and Lorenzo's Oil.

X-linked adrenoleukodystrophy is a rare, neurodegenerative peroxisomal disorder connected with mutation in the ABCD1 gene, causing impairment of the peroxisomal ß-oxidation process and in consequence, accumulation of very long-chain fatty acids (VLCFA) in blood and tissues. In this study we present serum very long-chain fatty acids levels during clinical course in an X-linked adrenoleukodystrophy patient after haematopoietic stem cell transplantation (HSCT) and on Lorenzo's Oil in a 11 years' period. The patient was diagnosed at the age of 8 months by family screening. The administration of LO was started at 2 years of age. HSCT from a family donor was performed twice. VLCFA serum levels were detected by the GC method. Chimaerism subsequent to HSCT was also analyzed. Increasing very long-chain fatty acids levels correlate with a decreasing chimaerism level after haematopoietic stem cell transplantation. The sequential monitoring of very long-chain fatty acids serum levels is important and useful for assessment of engraftment, graft failure or rejection.

Determination of urinary D-/L-arabinitol ratios as a biomarker for invasive candidiasis in children with cardiac diseases.

A non-invasive, non-culture-based method of determining urinary D-/L-arabinitol (D-/L-ARA) ratios was investigated as a tool for the diagnosis of invasive candidiasis in nosocomial paediatric infection cases. The study encompassed 138 children aged 4 days to 16 years (mean ± SD=1.6 ± 4.2 years) with congenital heart defects (91.4%) or with rhythm disorders or circulatory failure (8.6%). ARA enantiomers were detected by GC using an electron capture detector. Positive D-/L-ARA ratios were found for 11/11 patients with proven candidiasis and 17/19 patients with clinically suspected invasive candidiasis. Thirty children were undergoing antifungal chemotherapy. D-/L-ARA ratios (mean ± SD) were 2.601 ± 0.544 in hospitalized cardiac patients without fungal infection and 5.120 ± 1.253 in those receiving antifungal therapy (P<0.001). The sensitivity of the method was 100%, the specificity 97.2%, the positive predictive value was 78.6% and the negative predictive value was 100%.

Urinary D-arabinitol/L-arabinitol levels in infants undergoing long-term antibiotic therapy.

Long-term antibiotic therapy is one of the main risk factors for mycosis. The urinary D-arabinitol/L-arabinitol (D-/L-ARA) ratio (a biomarker of several Candida species) was determined by gas chromatography with an electron capture detector in samples from 51 infants undergoing long-term antibiotic therapy. Although 47 of these children had higher D-/L-ARA ratios than healthy controls (P<0.0003), their values nonetheless remained within upper-normal limits (D-/L-ARA ratio of <3.6). Four children with suspected invasive candidiasis had above-normal ratios that normalized with fluconazole treatment.