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Forest ecosystems are of considerable significance for the conservation of plant biodiversity. Sweet chestnut (Castanea sativa Mill.) belongs to the hardwood forest species within the genus Castanea. It is dominant in mountainous forests of western Georgia occupying the majority of areas covered with forests. Because of low self-renewal and diseases, the large massifs of chestnut forests are threatened by extinction. Castanea sativa is included in the 'Red List' of Georgia under state vulnerable (VU) and has been subjected to conservation measures in response to the Global Strategy for Plant Conservation (GPSC). Rapidly developing in vitro techniques open new possibilities for the safe ex-situ conservation of woody plant material. Various tissue culture-derived explants, such as shoot tips, nodal explants, somatic embryos, embryogenic cell lines, and embryonic axes have been widely used for conservation purposes to ensure the sustainability of the genetic pool of the genus Castanea. The study summarizes the recent achievements in species protection in Georgia via long-term preservation of a Georgian provenance of sweet chestnut using embryonic axes (EA) as an explant. The present overview focuses on the successful utilization of zygotic embryos for the conservation of a Georgian provenance of sweet chestnut germplasm and summarizes the recent achievements via long-term preservation. The efficacy of different techniques for cryopreservation of EAs, such as specimen dehydration - 'one-step freezing', PVS2-vitrification, and encapsulation-vitrification are evaluated. The advantages of the utilization of zygotic embryos for safe and effective long-term conservation of threatened hardwoods concerning the post-cryopreservation recovery of explants are discussed.

The gene SURF1 encodes a factor involved in the biogenesis of cytochrome c oxidase, the last complex in the respiratory chain. Mutations of the SURF1 gene result in Leigh syndrome and severe cytochrome c oxidase deficiency. Analysis of seven unrelated patients with cytochrome c oxidase deficiency and typical Leigh syndrome revealed different SURF1 mutations in four of them. Only these four cases had associated demyelinating neuropathy. Three mutations were novel splicing-site mutations that lead to the excision of exon 6. Two different novel heterozygous mutations were found at the same guanine residue at the donor splice site of intron 6; one was a deletion, whereas the other was a transition [588+1G>A]. The third novel splicing-site mutation was a homozygous [516-2_516-1delAG] in intron 5. One patient only had a homozygous polymorphism in the middle of the intron 8 [835+25C>T]. Western blot analysis showed that Surf1 protein was absent in all four patients harboring mutations. Our studies confirm that the SURF1 gene is an important nuclear gene involved in the cytochrome c oxidase deficiency. We also show that Surf1 protein is not implicated in the assembly of other respiratory chain complexes or the pyruvate dehydrogenase complex.

SummaryThis anatomical investigation on olive secondary somatic embryos describes several aspects of embryo development, including proembryoid origin and growth, aspects of tissue differentiation, localization of somatic embryogensis, and starch occurrence. The failure of a number of secondary somatic embryos to develop into perfect structures is to be ascribed to defects in the last growth stages (fused embryos, fused cotyledons) and/or to tissue degeneration processes affecting both imperfect and apparently perfect somatic embryos.

SummaryFlower bud induction in the olive is a long lasting process, influenced by a number of factors, both internal and external to the tree. Research results seem to confirm the hypothesis of a two-step induction, eventually leading to the onset of flower bud differentiation, which appears to be started at the end of autumn. The paper examines the various aspects of this important issue in olive flower biology, by reviewing a large number of research papers produced over almost a century.

We have previously reported a genetic study of a neonatal lactic acidosis linked to a pyruvate dehydrogenase complex deficiency due to the absence of the protein X subunit. This rare autosomal recessive disorder is associated with specific deletions in this polypeptide which is encoded by the HsPDX1 gene, located on chromosome 11p1.3. The pathology of the patient was considered to arise from a large homozygous deletion (78del85) found at the 5' end of the HsPDX1 coding sequence. Her heterozygous mother underwent prenatal diagnosis during a subsequent pregnancy. Chorionic villus samples were used for three independent studies: (1) normal levels of the protein X component of the PDH complex were detected by immunoblotting; (2) RT-PCR analysis showed no deletion at the 5' end of the cDNA but the presence of a distinct heterozygous deletion (965del59) at its 3' end inherited from the father; (3) haplotype analysis revealed the presence of the father's mutated allele and the mother's normal allele. It was concluded that the fetus was heterozygous for this separate 3' deletion, so, it was likely to be not affected. This study permitted us to characterize more precisely the genetic abnormalities of the HsPDX1 cDNA occurring in each family's member.

This double-blind randomized study was designed to compare the efficacy and safety of calcipotriol ointment (50 microg/g) with betamethasone dipropionate (64 mg/g) and salicylic acid (0.03 g/g) ointment in the treatment of nail bed psoriasis. Fifty-eight patients applied the given drug to the affected nails twice a day for 3-5 months, depending on clinical response. Efficacy was assessed monthly on the basis of nail thickness, measured in millimetres. Photographs of the treated nails were taken at baseline, and after 3 and 5 months. Tolerability was assessed at 3 and 5 months. In patients with fingernail psoriasis, after 3 months of treatment subungual hyperkeratosis was reduced from 2.3 +/- 0.1 mm (mean +/- SEM) to 1.5 +/- 0.1 mm (-26.5%) in the calcipotriol group and from 2.3 +/- 0.1 mm to 1.6 +/- 0.1 mm (-30.4%) in the betamethasone dipropionate and salicylic acid group [not significant (NS) between treatments, analysis of variance (ANOVA)]. After 5 months, responders showed a 49.2% reduction in hyperkeratosis in the calcipotriol group (from 2.8 +/- 0.1 mm to 1.4 +/- 0.2 mm) and 51.7% (from 2.1 +/- 0.1 mm to 1.0 +/- 0.1 mm) in the betamethasone dipropionate and salicylic acid group (P < 0.001 from baseline, NS between treatments, ANOVA). In patients with toenail psoriasis, after 3 months of treatment there was an overall reduction in hyperkeratosis from 2.6 +/- 0.1 mm to 2.1 +/- 0.1 mm (-20.1%) in the calcipotriol group and from 3.0 +/- 0.1 mm to 2.3 +/- 0.1 mm (-22. 9%) in the betamethasone dipropionate and salicylic acid group (P < 0.001 from baseline, NS between treatments, ANOVA). By the end of the fifth month there was a 40.7% reduction in hyperkeratosis in the calcipotriol group (from 2.1 +/- 0.1 mm to 1.2 +/- 0.1 mm) and 51.9% in the betamethasone dipropionate and salicylic acid group (from 2.7 +/- 0.1 mm to 1.3 +/- 0.1 mm; P < 0.0001 from baseline, NS between treatments, ANOVA). The results of the study show that calcipotriol is as effective as a combination of a topical steroid with salicylic acid in the treatment of nail psoriasis and represents a safe alternative in the topical treatment of nail psoriasis.

The pyruvate dehydrogenase complex (PDHc) is a multienzyme complex consisting of three catalytic and two regulatory enzymes, as well as a less well defined subunit called protein X. PDHc deficiency is a common cause of congenital lactic acidosis. Most patients with PDH deficiency have a mutation in the alpha chain of the PDH E1 enzyme. Very few patients have been described in whom the basic defect of a PDH deficiency is situated in the X protein. We studied a boy with severe lactic acidosis and developmental delay in whom a deficiency of PDH activity led to further investigations. Immunochemical analysis with anti-PDHc antibodies demonstrated an absence of the X component. This report is the fourth family in which an abnormal protein X has been found. In cases with PDH deficiency where no mutation of the PDHE1 alpha gene is found, further investigations by means of immunoblotting with specific antibodies against the different subunits should be performed.

We report studies of four patients with pyruvate dehydrogenase complex (PDH) deficiency caused by mutations in the E1 alpha subunit. Two unrelated male patients presented with Leigh syndrome and a R263G missense mutation in exon 8. This mutation has previously been described in males with the same phenotype. The two other patients had different novel mutations: (1) an 8-bp deletion at the C-terminus (exon 11) was found in one allele of a young girl suffering from microcephaly and (2) a C88S missense mutation (exon 3) in a boy who only presented with motor neuropathy. These mutations were not found in the mothers of any of the four cases. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in three out of the four patients. These findings confirm that: (1) PDH deficiencies are genetically heterogeneous, (2) the R263G mutation is more frequent in male cases than are other mutations and this amino acid is a hot spot for gene mutations, (3) the last eight amino acids may be important for the conformation of the tetrameric E1-PDH enzyme, and (4) the amino acids at positions 88, 263 and 382-387 are essential for the linking of the alpha subunit with the beta subunit and for the activity of the holoenzyme.

Background: Spitz nevus has clinically been described as a dome-shaped usually nonpigmented papular or nodular lesion variable in color from pink to red. Objectives: To give an exhaustive description of the clinical features of the Spitz nevus from a large series of 247 patients. Methods: A retrospective analysis of the clinical features of 247 Spitz nevi excised from 1974 to 1993 has been performed. We evaluated the following features: age, sex, anatomical location, clinical and histopathologic features; descriptive statistics were calculated and relationships among the above variables were assessed. Results: Most lesions were pigmented (71.7%), located on the lower extremities (43.3%), more frequent in the first decade (55.8%) and in females (57.9%). The nonpigmented type was more frequent in the head or neck region, whereas the pigmented types were more frequent on the lower extremities. Besides, these types showed different histopathologic features: the spindle cells usually predominated in the flat pigmented type, whereas dome-shaped types were usually composed of both spindle and epithelioid cells. Conclusions: In our patients, the pigmented Spitz nevi were more common than the nonpigmented ones; furthermore pigmented and nonpigmented Spitz nevi showed different anatomical locations and different histopathologic features.

Studies of human pyruvate dehydrogenase (PDH) deficiency have shown that defects in the E1 component are not common, with only a small number of defects associated specifically with the E3, E2, and component X subunits. We report here clinical, enzymatic, and immune studies of the PDH complex (PDHc) in a girl presenting with a primary defect in the component X. The patient, born from nonconsanguineous parents, presented with severe neonatal lactic acidosis, minor facial dysmorphia, and complete corpus callosum agenesis. The metabolic profile revealed marked hyperlactatemia and hyperpyruvic acidemia, with a normal lactate/pyruvate ratio and no detectable ketosis or hyperammonemia. The activity of total PDHc in cultured skin fibroblasts and in fresh mononuclear cells was markedly decreased by about 80% as compared with the controls and with the parents.

Most of the mutations causing deficiency of the pyruvate dehydrogenase (PDH) complex are in the X-linked E ^ gene. We have developed a rapid screening method for the detection of mutations in this gene using reverse transcription of total RNA, polymerase chain reaction amplification of the whole coding region of the gene and single-strand conformation polymorphism (SSCP) analysis. With this method, we studied eight patients with a PDH complex deficiency, using cultured fibroblasts. In all patients, aberrant SSCP patterns were found and, after sequencing of the corresponding fragments, we were able to identify six new mutations and two mutations already described previously. The mutations are point mutations leading to amino acid substitutions (5) and direct repeat insertions (3). The presence of the mutations was confirmed in genomic fibroblast DNA* The 4 female patients were shown to carry both a normal and a mutated Exa gene. © 1996 Wiley^Liss, Inc, k e y w o r d s : Pyruvate dehydrogenase Eta, RT-PCR, SSCP, Mutation analysis

Pyruvate dehydrogenase (PDH)-Elα deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial Elα deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of “malaises.” In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-Elα and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-Elα deficiency is strongly suspected.

We identified a new Y243S mutation in the X-linked E1 α-PDH gene in a patient with pyruvate dehydrogenase complex (PDHc) deficiency. The activity in cultured fibroblasts was very low even in the presence of high thiamine pyrophosphate (TPP) concentrations, indicating that the defect could be due to decreased affinity of PDHc for TPP.

In this study, the efficiency of three vitrification-based cryopreservation techniques, i.e. vitrification, encapsulation-vitrification and droplet-vitrification were compared for cryopreserving Sequoia sempervirens apical and basal buds sampled from in vitro shoot cultures. The effect of cold-hardening of mother-plants and of bud culture medium and sucrose preculture was also investigated. Culture of apical and basal buds sampled from cold-hardened mother-plants on Quoirin and Lepoivre medium with activated charcoal had a positive effect on regrowth. Only droplet-vitrification ensured survival and regrowth after cryopreservation. After cryopreservation, regeneration of apical buds was possible for PVS2 exposure durations between 90 and 180 min but it remained low, with a maximum of 18 percent after 135 min treatment. With basal buds, regeneration after cryopreservation was possible over a larger range of PVS2 treatment durations, between 30 and 180 min. The highest regeneration percentage was slightly higher (22 percent) than that measured with apical buds, and was also achieved after 135 min PVS2 exposure.

Among the many metabolic encephalomyelopathies caused by deficiencies in the pyruvate dehydrogenase complex (PDHC), nearly all involve its E1 subunit. We describe two new familial cases of PDHC deficiency with encephalomyelopathy, chronic lactic acidemia, and a normal E1 subunit of PDHC but deficiency in another component. Activity of PDHC was measured in cultured skin fibroblasts and skeletal muscle, and immunoblot studies were performed on mitochondrial extracts from skin fibroblasts. Spectra of muscle tissue, obtained in vivo with phosphorus 31 nuclear magnetic resonance, were recorded both at rest and with exercise. The PDHC activity was markedly reduced to 10% to 20% of normal values in both cultured skin fibroblasts and skeletal muscle. Immunoblotting of skin fibroblast mitochondrial extracts showed a specific deficiency in the protein X component of PDHC but normal E1, E2, and E3 components. Spectra obtained with 31P nuclear magnetic resonance showed alterations compatible with those found in mitochondrial myopathies. This is the second description of an encephalomyelopathy associated with a specific absence of the lipoyl-containing protein X component, which has a structural role in the formation of a functional PDHC.

The technique of the use of multi-annular opposed jets as different from using swirl and bluff body creates an excellent recirculation zone with desired size in a large space. The size of recirculation, the magnitude of reverse velocity and turbulence intensity are much greater than those formed by bluff body. Factors affecting the flowfield include the velocity ratio of the opposed jets to the primary airJ, the diameter and construction of the opposed jet ring, secondary air velocity and configuration, and confined or unconfined flow condition and so on. This method is a promising way for flame stabilization in combustion technology.

Strawberry tree (Arbutus unedo L.), an evergreen shrub, is a post-fire resprouting species in the Mediterranean maquis, relevant for its ornamental value and utilised for fruit, honey, charcoal and fodder production. Seed and cutting propagation is currently used by nurseries. This paper investigates in vitro establishment, shoot elongation, proliferation and rooting of strawberry tree in vitro germinated seedlings, as well as callus induction from different explants. The best results in terms of non infected seeds and germination rate were obtained by disinfecting seeds in a 7% NaClO solution for 1 min. Axillary shoot development was relevant on apices cultured in a WPM medium with 22.2 ?M BA. A light intensity of 25 ?mol·m-2·s -1, in comparison with 40 ?mol·m-2·s -1, increased shoot elongation and axillary bud formation. Genotype noticeably influenced axillary shoot formation. Microcuttings rooted better when pulsed with 0.3 or 0.6 mM IBA for 15 min as compared to continuative treatment and trasferred to auxin-free medium. Yellow friable calluses were obtained from internodes, foliar discs and root cuttings cultured in 1/2 N - MS basal salts and vitamins supplemented with zeatin (1 and 5 ?M) being the largest those derived from internodes and cultured with the highest zeatin level.

We identified a new Y243S mutation in the X-linked E1 alpha-PDH gene in a patient with pyruvate dehydrogenase complex (PDHc) deficiency. The activity in cultured fibroblasts was very low even in the presence of high thiamine pyrophosphate (TPP) concentrations, indicating that the defect could be due to decreased affinity of PDHc for TPP.

Hyperinsulinism and hyperammonemia syndrome has been reported as a cause of moderately severe hyperinsulinism with diffuse involvement of the pancreas. The disorder is caused by gain of function mutations in the GLUD1 gene, resulting in a decreased inhibitory effect of guanosine triphosphate on the glutamate dehydrogenase (GDH) enzyme. Twelve unrelated patients (six males, six females) with hyperinsulinism and hyperammonemia syndrome have been investigated. The phenotypes were clinically heterogeneous, with neonatal and infancy-onset hypoglycemia and variable responsiveness to medical (diazoxide) and dietary (leucine-restricted diet) treatment. Hyperammonemia (90-200 micromol/L, normal

Dermoscopy improves sensitivity in the diagnosis of melanoma. We have developed a new diagnostic dermoscopic method which evaluates only seven dermoscopic features or criteria. We called the method Seven features for melanoma (7FFM). To present and to evaluate the reproducibility of our dermoscopic diagnostic method (7FFM) we held eight dermoscopic courses from 10/4/96 to 04/03/98 in various Italian cities. In fact the reliability of a diagnostic test or method mainly depends on the level of agreement in the interpretation of results among different observers. Only methods with good agreement can be used in clinical practice for the diagnosis of melanoma. Many dermatologists (207) attended one of the eight dermoscopic courses: each course was one-day in length and at the end of the course the participants evaluated a set of 25 dermoscopic slides using our dermoscopic method. Percentages of concordance and K values for a kappa statistical analysis to evaluate inter-rater reliability have been calculated. The method showed a mean percentage of concordance of 85.7%, median 88%, a mean K value of 0.699, median 0.684. These data point to a good agreement level. Our method shows good reproducibility after a short training program.

We have previously reported a genetic study of a neonatal lactic acidosis linked to a pyruvate dehydrogenase complex deficiency due to the absence of the protein X subunit. This rare autosomal recessive disorder is associated with specific deletions in this polypeptide which is encoded by the HsPDX1 gene, located on chromosome 11p1.3. The pathology of the patient was considered to arise from a large homozygous deletion (78del85) found at the 5' end of the HsPDX1 coding sequence. Her heterozygous mother underwent prenatal diagnosis during a subsequent pregnancy. Chorionic villus samples were used for three independent studies: (1) normal levels of the protein X component of the PDH complex were detected by immunoblotting; (2) RT-PCR analysis showed no deletion at the 5' end of the cDNA but the presence of a distinct heterozygous deletion (965del59) at its 3' end inherited from the father; (3) haplotype analysis revealed the presence of the father's mutated allele and the mother's normal allele. It was concluded that the fetus was heterozygous for this separate 3' deletion, so, it was likely to be not affected. This study permitted us to characterize more precisely the genetic abnormalities of the HsPDX1 cDNA occurring in each family's member.

The clinical diagnosis of melanoma has a mean sensitivity of 67%, dermoscopy or dermatoscopy is a non invasive technique which improves this sensitivity. Our purpose was to create a simple dermoscopic method for the diagnosis of melanoma useful in daily office practice. For this reason a training set of 218 cutaneous pigmented lesions was used and scored for 16 dermoscopic features: for each feature sensitivity, specificity and statistical significance were evaluated. The results were used to create a simple dermoscopic diagnostic method of only seven dermoscopic features (7FFM). The method was used to evaluate a test set of 713 pigmented skin lesions consecutively observed. The diagnostic dermoscopic method developed gave a sensitivity of 94.6%, a specificity of 85.5% and an efficiency of 87.6%. Our method improves the sensitivity in the diagnosis of melanoma and can be used for the screening of pigmented skin lesions.

This double-blind randomized study was designed to compare the efficacy and safety of calcipotriol ointment (50 microg/g) with betamethasone dipropionate (64 mg/g) and salicylic acid (0.03 g/g) ointment in the treatment of nail bed psoriasis. Fifty-eight patients applied the given drug to the affected nails twice a day for 3-5 months, depending on clinical response. Efficacy was assessed monthly on the basis of nail thickness, measured in millimetres. Photographs of the treated nails were taken at baseline, and after 3 and 5 months. Tolerability was assessed at 3 and 5 months. In patients with fingernail psoriasis, after 3 months of treatment subungual hyperkeratosis was reduced from 2.3 +/- 0.1 mm (mean +/- SEM) to 1.5 +/- 0.1 mm (-26.5%) in the calcipotriol group and from 2.3 +/- 0.1 mm to 1.6 +/- 0.1 mm (-30.4%) in the betamethasone dipropionate and salicylic acid group [not significant (NS) between treatments, analysis of variance (ANOVA)]. After 5 months, responders showed a 49.2% reduction in hyperkeratosis in the calcipotriol group (from 2.8 +/- 0.1 mm to 1.4 +/- 0.2 mm) and 51.7% (from 2.1 +/- 0.1 mm to 1.0 +/- 0.1 mm) in the betamethasone dipropionate and salicylic acid group (P0.001 from baseline, NS between treatments, ANOVA). In patients with toenail psoriasis, after 3 months of treatment there was an overall reduction in hyperkeratosis from 2.6 +/- 0.1 mm to 2.1 +/- 0.1 mm (-20.1%) in the calcipotriol group and from 3.0 +/- 0.1 mm to 2.3 +/- 0.1 mm (-22. 9%) in the betamethasone dipropionate and salicylic acid group (P0.001 from baseline, NS between treatments, ANOVA). By the end of the fifth month there was a 40.7% reduction in hyperkeratosis in the calcipotriol group (from 2.1 +/- 0.1 mm to 1.2 +/- 0.1 mm) and 51.9% in the betamethasone dipropionate and salicylic acid group (from 2.7 +/- 0.1 mm to 1.3 +/- 0.1 mm; P0.0001 from baseline, NS between treatments, ANOVA). The results of the study show that calcipotriol is as effective as a combination of a topical steroid with salicylic acid in the treatment of nail psoriasis and represents a safe alternative in the topical treatment of nail psoriasis.

Psoriasis is present all over the world and its prevalence varies in the different populations and different geographical areas. For example, Northern European countries seem to have rates of incidence which are greater than those known for Southern Europe. However, today there is still a lack of adequate data to allow comparisons at an international level.In Italy in 1994 the AISP (Interdisciplinary Association for the Study of Psoriasis) co-ordinated the recording of monthly case histories and clinical results relating to psoriasis in patients observed in dermatology centres homogeneously distributed throughout Italy. The results were extrapolated from the overall case series.A sample of nearly 8000 cases was collected, most presenting psoriasis vulgaris. This pathology, prevalent in males, first appears at an age somewhere between the teens and twenties. Numerous factors may be involved, and onset is mainly attributed to stress, viral or bacterial infections and pharmacological therapy. Over 90% of cases lost between 1 and 7 working days in the course of the year. Local anti-psoriasis treatment in monotherapy was administered more frequently than systemic therapy or combined therapy.The results of this first Italian epidemiological study confirm that psoriasis is homogeneously distributed throughout the country. About 50% of patients avail themselves of specialist cures, even several times in the course of the year, and use a wide range of therapies which may be more or less demanding. The internal socio-economic cost of the disease is evident, particularly in terms of working days lost and/or medical expenses.

TachoComb is a new, ready-to-use hemostatic agent consisting of a collagen sheet coated on one side with human fibrinogen, bovine thrombin, and bovine aprotinin. The product was used in 125 surgical operations (vascular, hepatic, urological and ENT) in which secondary hemostasis was required. It was placed over the cut surface or over the edges of the wound. The investigating surgeons expressed their opinion on the intra- and postoperative hemostatic efficacy, and routine laboratory tests were done postoperatively. TachoComb had good hemostatic efficacy in 67.2% of cases, and very good in 22.4%. No noteworthy systemic changes were observed. As an adjuvant to obtain complete hemostasis in surgery, TachoComb is effective, practical and quick to use, and is very well tolerated.

Most of the mutations causing deficiency of the pyruvate dehydrogenase (PDH) complex are in the X-linked E1 alpha gene. We have developed a rapid screening method for the detection of mutations in this gene using reverse transcription of total RNA, polymerase chain reaction amplification of the whole coding region of the gene and single-strand conformation polymorphism (SSCP) analysis. With this method, we studied eight patients with a PDH complex deficiency, using cultured fibroblasts. In all patients, aberrant SSCP patterns were found and, after sequencing of the corresponding fragments, we were able to identify six new mutations and two mutations already described previously. The mutations are point mutations leading to amino acid substitutions (5) and direct repeat insertions (3). The presence of the mutations was confirmed in genomic fibroblast DNA. The 4 female patients were shown to carry both a normal and a mutated E1 alpha gene.

Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of "malaises." In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.

Pyruvate dehydrogenase deficiency is one of the most common causes of encephalopathy associated with lactic acidosis and is known to account for congenital lactic acidosis, recurrent ataxia, and infantile Leigh syndrome. Hitherto, however, peripheral neuropathy has not been regarded as a presenting symptom of pyruvate dehydrogenase deficiency. Here, we report on a boy who presented peripheral neuropathy with severe limb hypotonia, absent deep-tendon reflexes, and reduced motor nerve conduction velocities at 8 months of age. Persistent hyperpyruvicemia with normal lactate/pyruvate molar ratios in plasma were highly suggestive of a pyruvate dehydrogenase deficiency, and the determination of pyruvate dehydrogenase activity in circulating lymphocytes led to the diagnosis of pyruvate decarboxylase (PDH-E1) deficiency in the proband. Based on this observation, we suggest that pyruvate dehydrogenase deficiency should be considered in the diagnosis of peripheral neuropathy in infancy, especially when associated with persistent hyperpyruvicemia, normal lactate/pyruvate molar ratios in plasma, and recurrent episodes of drowsiness and hypotonia of unknown origin. (J Child Neurol 1994;9:52-55).

(1992). Treatment of steatocystoma multiplex with isotretinoin. Journal of Dermatological Treatment: Vol. 3, No. 3, pp. 160-161.