Rhabdomyolysis and acute encephalopathy in late onset medium chain acyl-CoA dehydrogenase deficiency

High-frequency sonography has been shown to be a useful tool in planning operative strategy in the surgery of malignant melanoma (MM). The purpose of the present study was to compare sonometric and histometric data of tumour thickness in primary cutaneous MM, applying statistical methods in order to evaluate the pre-operative relevance of sonometry. The thickness of 259 melanomas was measured preoperatively by a 20-MHz B scan, and postoperatively by histometry. Statistical analysis was performed using Pearson's correlation coefficient and absolute and relative differences. Although the correlation between sonometry and histometry was good (r = 0.88), there was a mean difference of 0.39 mm (relative difference 28%). Overall, sonometry was in agreement with the corresponding histological classes in 75% of cases. However, tumours assessed by ultrasound as between 0.55 and 0.95 mm thick were incorrectly classified according to histology in 34%, and those between 1.30 and 1.70 mm were incorrectly classified in 50% of cases. Our data reveal greater differences between sonometry and histometry using appropriate statistical methods. A concept to assess differences between sonometry and histometry is recommended.     

Pregnancy complications are frequent in long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency

Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1alpha. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1alpha activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1alpha for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1alpha). Similarly, HCC-1 was less potent than MIP-1alpha in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was approximately 100-fold lower than that of MIP-1alpha (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.     

Retinal abnormalities in experimental vitamin E deficiency

Physiological and biochemical studies have been carried out longitudinally over a period of 12 months in vitamin E deficient and control rats to gain an understanding of the mechanism whereby vitamin E conserves normal retinal function. Electroretinographic studies indicated that the primary effect of vitamin E deficiency was on the photoreceptors. Ultrastructural studies, however, did not show any morphological changes to the photoreceptors which could explain receptor dysfunction. A 30-40% loss of vitamin A (retinol) was found to be associated with vitamin E deficiency. This could be corrected by repletion with vitamin E, but there was no associated improvement in visual function. An irreversible loss of the long-chain polyunsaturated fatty acids from the retina, increased lipid peroxidation and alterations in membrane fluidity were also detected during vitamin E deficiency. We suggest that a deficiency of vitamin E leads to changes in the membrane microenvironment, which could affect photo transduction by either impairing the ability of rhodopsin to undergo conformational changes to the active form, or by disrupting the hyperpolarising and depolarising processes of the photoreceptors.     

Studies on long chain cis- and trans-acyl-CoA esters and Acyl-CoA dehydrogenase from rat heart mitochondria

A quantitative counterimmunoelectrophoresis technique has been applied to evaluation of RNA antibodies in serum and unconcentrated CSF. Serum anti-RNA antibodies have been found at high dilutions in some patients with infectious diseases, subacute panencephalitis and multiple sclerosis. RNA antibodies in CSF are significantly linked to oligoclonal aspect, i.e. to a synthesis of IgG inside the CNS.     

Retinal functions in dominant cystoid macular dystrophy (DCMD)

Dominant cystoid macular dystrophy (DCMD) occurred in 28 members of 5 unrelated families. The disease is characterized by cystoid macular oedema and leakage from retinal capillaries in the posterior pole. Colour vision examination reveals a type I red-green defect with concomitant blue-yellow defectiveness; the latter may be caused by the leaking capillaries. The ERG is normal. The EOG is subnormal. Darkadaptation curves are often slightly disturbed. There are frequently also aspecific pigmentary alterations in the peripheral fundus.     

Clinical diversity of pyruvate dehydrogenase deficiency

Clinical features, magnetic resonance, and biochemical studies are reported in 7 children with pyruvate dehydrogenase (PDH) deficiency. These findings confirm the diverse clinical presentation of this condition, although neurological abnormalities are consistent features. Imaging results are also varied. Six of the children were investigated with proton magnetic resonance spectroscopy and lactate was demonstrated in brain in all patients. Regional variation in the lactate signal was observed in those patients in whom 2 regions were examined. Advances in molecular genetics have provided some explanations for the clinical variation in pyruvate dehydrogenase deficiency.     

Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency

People with the variants of glucose-6-phosphate dehydrogenase (GPD) deficiency common in the southern Chinese (Canton, B(-)Chinese, and Hong Kong-Pokfulam) have a moderate shortening of red-cell survival but no anaemia when they are in the steady state. With a cross-transfusion technique, primaquine, nitrofurantoin, and large doses of aspirin were found to aggravate the haemolysis while sulphamethoxazole did so only in some people. Individual differences in drug metabolism may be the reason for this. Many commonly used drugs reported to accentuate haemolysis in GPD deficiency did not shorten red-cell survival.     

Glucose-6-phosphate dehydrogenase deficiency in a dog

After screening 3,300 dogs, one animal with a mild deficiency of erythrocyte G6PD was detected. Although it had several clinical problems for 2 months, no abnormality could be directly attributable to the reduced enzymatic activity. Biochemically the mutant was electrophoretically slower but within the normal range for Km-G6P, Km-NADP, use of 2-dG6P and deamino NADP, pH optimum, and heat stability.     

Myophosphorylase deficiency and limb-girdle muscular dystrophy in the same pedigree

We report 2 familial patients with limb-girdle muscular dystrophy (LGD). The parents of patient 1 showed a consanguineous marriage and patient 2 was a paternal cousin of patient 1. Slowly progressive muscular weakness/wasting and dystrophic changes in the biopsied muscles were observed in both patients. However, a quantitative assay revealed a severely reduced myophosphorylase activity in patient 1 with normal activity in patient 2. A semi-ischemic exercise test disclosed no elevation of venous lactate in patient 1 with a normal increase in patient 2. A leukocytes DNA analysis in patient 1 did not show the gene deficits previously recognized in patients with McArdle's disease (McD). Patient 1 may only have abnormal myophosphorylase activity with dystrophic changes secondary to the myophosphorylase deficiency or coincidentally two genomic abnormalities for McD and LGD. LGD still has heterogenous etiologies and the responsible genes for these two disorders may be closely mapped.     

Beneficial effects of L-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency

The rapid effects of glucocorticoids(GCs) on the Na+dependent, high affinity uptake of 3[H]-L-glutamate(Glu) in rat cerebral cortex synaptosomes(4 min incubation) and human neuroblastoma clone SK-N-SH (10min preincubation and 5 min incubation) were investigated. GCs, including corticosterone, corticosterone-sulfate, hydrocortisone-hemisuccinate and dexamethasone 21-phosphate(DEX) were found stimulating Glu uptake. The uptakes in synaptosomes and SK-N-SH cells were increased to 117-126% and 121-137% respectively of the control by 10(-6)mol/L GCs. The stimulation of GCs was dose-dependent. The maximal effect of DEX in SK-N-SH cells appeared at10(-7)mol/L, and the least effective dose of DEX was at 10(-9)mol/L. Guanosine 5-O-(2-thiodiphosphate), an inhibitor of G-protein activation, could block the stimulation of GCs. The results indicated that GCs rapidly enhance the Na+-dependent high affinity Glu uptake in nerve endings and SK-N-SH cells, even at the concentration of physiological conditions, and the G-protein on synaptic membranes or SK-N-SH cell membranes might be involved in the effect of GCs.     

Glucose-6-phosphate dehydrogenase deficiency and malaria

Glucose-6-phosphate dehydrogenase (G6PD) is a cytoplasmic enzyme that is essential for a cell's capacity to withstand oxidant stress. G6PD deficiency is the commonest enzymopathy of humans, affecting over 400 million persons worldwide. The geographical correlation of its distribution with the historical endemicity of malaria suggests that 66PD deficiency has risen in frequency through natural selection by malaria. This is supported by data from in vitro studies that demonstrate impaired growth of P. falciparum parasites in G6PD-deficient erythrocytes. Attempts to confirm that G6PD deficiency is protective in field studies of malaria have yielded conflicting results, but recent results from large case control studies conducted in East and West Africa provide strong evidence that the most common African G6PD deficiency variant, G6PD A-, is associated with a significant reduction in the risk of severe malaria for both G6PD female heterozygotes and male hemizygotes. The effect of female homozygotes on severe malaria remains unclear but can probably be assumed to be similar to that of comparably deficient male hemizygotes.     

Glucose-6-phosphate dehydrogenase deficiency with psychosis

Several authors have attempted to establish a correlation between glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and chronic schizophrenia, and the results were contradictory. We propose that the correlation between G-6-PD deficiency and schizophrenia is to be found in the form of an acute delirium.     

Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews

PURPOSE: To measure binocular function and patient satisfaction with monovision induced by photorefractive keratectomy (PRK) in myopic presbyopic patients. SETTING: Refractive Department, Cleveland Clinic, Cleveland, Ohio, USA. METHODS: This study comprised 21 myopic presbyopic patients with monovision induced by PRK. Sixteen emmetropic patients who had PRK served as a control group. Monovision was induced by undercorrecting the nondominant eye by 1.25 diopters for near vision and correcting the dominant eye with emmetropia for distance vision. Monocular and binocular uncorrected Snellen visual acuities at 20 feet and 13 inches, manifest refraction, ocular dominance, stereopsis at 20 feet and 13 inches, monocular and binocular contrast sensitivities, Worth-4-Dot test at 20 feet and 1/3 of a meter, and fusional convergence amplitudes were examined in each patient. RESULTS: In the monovision group at near and distance, 20 patients (95.3%) had binocular visual acuity of 20/25 or better. No patient in the monovision group used reading glasses postoperatively; 4 of 16 patients (25.0%) in the control group used such glasses. All patients maintained binocular fusion and stereo acuity ranging from 40 to 800 seconds of arc. Mean patient satisfaction was 86% (range 40% to 100%). In the control group, 12 patients (75.0%) had binocular distance visual acuity of 20/25 or better and 11 (68.8%) had binocular near visual acuity of 20/25 or better. CONCLUSION: Monovision PRK patients had better near vision than control PRK patients, with minimal compromise in stereo acuity and overall high patient satisfaction.     

Glucose-6-phosphate dehydrogenase deficiency in an 81-year-old

In a 81-year-old woman, who for many years had been treated with iron and vitamin B12 injections because of a 'tendency to anaemia', congenital haemolytic anaemia on the basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency was diagnosed. The iron and vitamin medication was discontinued and after a blood transfusion because of signs of heart failure, the patient could leave the hospital in good condition. After instruction with regard to provocative factors, like eating of broad beans, no more haemolytic events occurred. Of her children and grandchildren, 2 sons and 1 granddaughter were G6PD deficient.     

Changes of laminin beta 2 chain expression in congenital muscular dystrophy

We studied the distribution of laminin beta 2 chain in the skeletal muscle basement membrane of 16 patients with congenital muscular dystrophy (CMD) by immunohistochemistry. A dramatic reduction in the laminin beta 2 staining was observed in four patients with classical merosin-negative CMD. A moderate reduction of laminin beta 2 labelling was observed in four patients with partial merosin deficiency and two patients with merosin-positive CMD. Two patients with merosin-positive CMD had no apparent changes in the expression of laminin beta 2. In three patients and one fetus diagnosed as Walker-Warburg syndrome (WWS) the laminin beta 2 pattern was similar to normal controls. We conclude that a primary deficiency in the laminin alpha 2 chain may lead to a vast or moderate reduction in the laminin beta 2 chain in the skeletal muscle membrane.     

L-(+)-lactate dehydrogenase deficiency is lethal in Streptococcus mutans

The previously cloned gene for L-(+)-lactate dehydrogenase (LDH) from Streptococcus mutans was mutagenized in vitro. An Escherichia coli transformant which expressed a thermolabile LDH activity was identified. The ldh(Ts) gene was introduced into S. mutans on a suicide vector to create a heterodiploid expressing both wild-type and thermolabile LDH activities. Self-recombinants which had only one ldh gene were isolated. One of these clones expressed only the thermolabile LDH activity. This isolate grew well at 30 degrees C but did not grow at 42 degrees C under a variety of cultivation conditions, thereby proving that LDH deficiency is lethal in S. mutans in the absence of compensatory mutations.     

Molecular genetics of glucose-6-phosphate dehydrogenase deficiency in Mexico

PURPOSE: To report the results of a prospective study of the incidence of peripheral visual field loss after macular hole surgery. METHODS: Prospectively, 30 eyes of 30 consecutive patients with full-thickness macular holes operated on between December 1995 and April 1996 had preoperative and postoperative Goldmann visual field tests. The surgical procedure consisted of three-port pars plana vitrectomy, posterior hyaloid removal, nonexpansile fluid-hexafluoroethane (C2F6) exchange, and, in 19 of 30 patients, autologous platelet injection, followed by face-down positioning. RESULTS: Twenty-nine of these 30 cases were considered to be anatomic successes. Comparison of preoperative and postoperative visual fields disclosed that four patients (13%) had a peripheral scotoma, including one patient with stage 4 macular hole. Three other patients (10%) had a postoperative relative arcuate defect. Mean postoperative intraocular pressure was higher in the latter group. None of the patients complained of peripheral scotoma. CONCLUSIONS: Overall, seven of 30 patients (23%) had a postoperative visual field defect. Two categories of scotomas were observed: peripheral and relative arcuate. The cause of peripheral visual field loss is unclear. Increased intraocular pressure may be the cause of relative arcuate scotomas.