Autistic children exhibit distinct plasma amino acid profile.

In order to ascertain whether autistic children display characteristic metabolic signatures that are of diagnostic value, plasma amino acid analyses were carried out on a cohort of 138 autistic children and 138 normal controls using reverse-phase HPLC. Pre-column derivatization of amino acids with phenyl isothiocyanate forms phenyl thio-carbamate derivates that have a λmax of 254 nm, enabling their detection using photodiode array. Autistic children showed elevated levels of glutamic acid (120 ± 89 vs. 83 ± 35 mmol/L) and asparagine (85 ± 37 vs. 47 ± 19 mmol/L); lower levels of phenylalanine (45 ± 20 vs. 59 ± 18 mmol/L), tryptophan (24 ± 11 vs. 41 ± 16 mmol/L), methionine (22 ± 9 vs. 28 ± 9 mmol/L) and histidine (45 ± 21 vs. 58 ± 15 mmol/L). A low molar ratio of (tryptophan/large neutral amino acids) × 100 was observed in autism (5.4 vs 9.2), indicating lesser availability of tryptophan for neurotransmitter serotonin synthesis. To conclude, elevated levels of excitatory amino acids (glutamate and asparagine), decreased essential amino acids (phenylalanine, tryptophan and methionine) and decreased precursors of neurotransmitters (tyrosine and tryptophan) are the distinct characteristics of plasma amino acid profile of autistic children. Thus, such metabolic signatures might be useful tools for early diagnosis of autism.

Disturbed methionine cycle intermediates, lipid peroxides, uric acid and fibronectin in relation to severity of preeclampsia

To evaluate the plasma levels of methionine cycle intermediates: S-adenosylmethionine [SAM] and S-adenosylhomocysteine [SAH]. lipid peroxides marker: malondialdehyde [MDA]. uric acid and cellular fibronectin [cFn] in preeclamptic patients and their relations to the severity of disease. This study included 35 preeclamptic primigravid women; 19 mild and 16 severe preeclampsia- Eighteen age-matched healthy primigravidas were chosen as control group. Plasma levels of adenosylmethionine [SAM], S-adenosylhomocysteine [SAH], lipid peroxides marker: malondialdehyde [MDA], uric acid and cellular fibronectin were compared between normal pregnant, mild and severe preeclamptic pregnant women. High Performance Liquid Chromatography equipped with a reversed-phase column-C 18, and UV detector at 254 nm was used to separate SAM and SAH. Serum uric acid and MDA levels have been assayed by colorimetric methods. Serum cellular fibronectin was estimated by ELISA. Statistical analysis was performed using Mann Whitney u test and Spearman correlation analysis. Plasma levels of SAH, MDA. and cellular fibronectin were significantly increased in mild and severe preeclamptic groups compared with control group [P<0.05]. Also. these parameters were significantly higher in severe preeclamptic group than mild preecpalmatic group [P<0.05]. However, uric acid levels showed a significant increase in severe preeclamptic group compared with mild preeclamptic and control groups [P<0.05] while insignificant difference was observed between mild preeclamptic and control group [P>0.05]. SAM levels were significantly decreased only in severe preecplamsia than control [P<0.05]. Moreover. there were positive correlation between cellular fibronectin and SAH, MDA and uric acid. Disturbed methionine cycle intermediates: s-adenosylhomocysteine and s-adenosylemethionine. lipid peroxides. uric acid and fibronectin are important factors in the pathogenesis of preeclampsia and are directly related to its severity. Furthermore, cellular fibroneccin correlated positively with SAH, MDA, and uric acid suggesting [that these parameters have a primary role in endothelial dysfunction

Tyrosinemia type I: a clinico-laboratory case report.

Progressive hepatocellular dysfunction in a neonate, resulting in elevated serum alpha-fetoprotein together with raised blood levels of tyrosine and methionine, a generalized amino aciduria and the absence of urinary delta-aminolevulinic acid and succinylacetone, suggests a diagnosis of tyrosinemia type Ib. Classical tyrosinemia type I arises from a deficiency of fumarylacetoacetate hydrolase while the variant tyrosinemia type Ib results from a deficiency of maleylacetoacetate isomerase.

Assessment of the role of hypephomccysteinemia and its metabolic consequences in the vascular access thrombosis among hemodialysis patients

The aim of this work was, to determine whether hyperhomocysteinemia and its metabolic consequences are associated with vascular access thrombosis in patients with end stage renal disease [ESRD], undergoing chronic hemodiahysis [HD]. This study included 3 groups. Group I: 15 ESRD patients on regular HD, with history of more than one episode of vascular access thrombosis. Group II: 15 ESRD patients on regular HD, with no episodes of vascular access thrombosis. Group III: 10 healthy, age and sex matched individuels as a control group. Plasma total homocysfeine [tHcy] and Von Willebrand Factor [vWF] were estimated by ELISA. Determination of plasma folate was done by Radioimmunoassay [RIA]. Plasma glutathione peroxidase activity was estimated by modified Paglia and Valentine method. Plasma methionine and cysteine levels were estimated by amino acid autoanalyser. plasma Hcy levels of both HD groups [GI and GII] were significantly higher than control groups [GIII] [F value = 44,487, P<0.0001], while no significant difference was found between GI and GII. Plasma folic acid levels of both patients' groups were significantly higher than control group [F value = 29.063, P<0.0001], while there was no significant difference between its level in GI and GII. Plasma vWF of HD patients with vascular access thrombosis [GI] was significantly higher than that of both GII and GIII and that of GII was significantly higher than GIII [F value = 62.010, P<0.0001]. Plasma glutathione peroxidase activity of both HD groups [GI and GII] was significantly lower than the control group [GIII] [F value = 69.446, P<0.0001], also its activity in patients with vascular access thrombosis [GI] was significantly lower than that of patients without vascular access thrombosis [GII]. Plasma cysteine and methionine levels of both HD groups were not significantly different from control group, also there was no significant difference in their levels between GI and GII. Plasma Hcy levels showed no significant correlation with number of vascular access thrombosis, whereas it showed a significant positive correlation with plasma vWF [r = 0.474, P<0.01] and negative correlation with plasma glutathione peroxidase activity [r = 0.643, P<0.0001]. From the previous study we concluded that: Hyperhomocyteinemia is not a direct cause of vascular access thrombosis. It is linked with increased plasma vWF levels. Endlothelial injury induced by hyperhomocysteinemia may be the cause. The lower levels of plasma glutathione peroxidase activity reflect increased oxidative stress induced by hyperhomocyteinemia in hemodialysis patients

Homocystinuria with congenital/developmental cataract.

The aim of the study is to screen patients for homocystinuria with and without cataract and analyse for homocystine and methionine. Fifty-eight samples from 29 patients, i.e., plasma and urine collected after overnight fasting were analysed by the screening test for homocystine, and paper chromatography for homocystine and methionine. Out of 29 homocystinuric patients, 24 had cataract. Only one had appreciable amounts of methionine in his serum. He also had mental retardation as expected and belongs to Type I. The other types did not have methionine but had only homocystine. There was no mental retardation or ectopia lentis. So they belonged to Types II, III or IV. As there is excess methionine in Type I, with low cystine, cataract may be due to deficiency of cysteine and reduced glutathione and might be averted by suitable therapy, i.e., high cystine-low methionine diet with B6. In other types with low methionine, cataract may be due to decreased availability of amino acids for the synthesis of lens proteins; the treatment of choice should be B12, and folate with methionine.

Classic homocystinuria: clinical, biochemical and radiological observations, and therapeutic outcome of 24 Saudi patients

We considered the clinical, biochemical and radiological findings, and response to pyridoxine [vitamin B6] of 24 classic homocystinuric patients [15 females, 9 males] diagnosed at King Faisal Specialist Hospital and Research Centre. Common clinical findings included ectopia lentis [20 patients], skeletal system involvement [18 patients], vascular system involvement [9 patients] and mental retardation [all patients to varying degrees]. A number of unusual findings were reported. The parents of 21 patients were first-degree relatives and 19 patients had at least one other family member affected by the same disease. Only 4 patients responded to pyridoxine; their methionine level decreased to almost normal range

Leucinose: estudo de um caso / Leucinosis: study of a case

Apresentaçäo de um caso de leucinose em recém-nascido do sexo feminino, diagnóstico no 26§ dia de vida. O quadro neurológico se caracteriza por alteraçöes do tono muscular, convulsöes, letargia e dificuldade respiratória. A demosntraçäo do aumento de aminoácidos de cadeia ramificada através do aminoacidograma constituiu o teste diagnóstico mais importante e o tratamento com MSUD resultou na boa evoluçäo da paciente