Biomedical subjects

M Pineda

Publications and source records attributed to M Pineda.

At least 37 records · Page 2Linked to original sources

PubMed2001

Oxidative stress in Rett syndrome.

The investigation of parameters that might influence the neurological evolution of Rett syndrome might also yield new information about its pathogenic mechanisms. Oxidative stress caused by oxygen free radicals is involved in the neuropathology of several neurodegenerative disorders, as well as in stroke and seizures. To evaluate the free radical metabolism in Rett syndrome, we measured red blood cell antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) and plasma malondialdehyde, as lipid peroxidation marker in a group of patients with Rett syndrome. No significant differences were observed in erythrocyte glutathione peroxidase, glutathione reductase and catalase activities, between the Rett syndrome patients and the control group. Erythrocyte superoxide dismutase activities were significantly decreased in Rett syndrome patients (P<0.001) compared with the control group. Plasma malondialdehyde concentrations were significantly increased in Rett syndrome patients (P<0.001). An unbalanced nutritional status in Rett syndrome might explain the reduced enzyme activity found in these patients. Our results suggest that free radicals generated from oxidation reactions might contribute to the pathogenesis of Rett syndrome. The high levels of malondialdehyde reflect peroxidative damage of biomembranes that may contribute to progressive dementia, impaired motor function, behavioural changes, and seizures, in Rett syndrome. We found a probable relationship between the degree of oxidative stress and the severity of symptoms, which should be further investigated with a larger number of patients in different disease stages.

Adolescent↗

PubMed2001

Rett syndrome in Spain: mutation analysis and clinical correlations.

Rett syndrome (RTT) is an X-linked neurodevelopmental disease that affects girls almost exclusively. In a high proportion of patients the disease is caused by de novo mutations at the MECP2 gene, encoding methyl-CpG-binding protein 2. With the aim to characterize the spectrum of mutations in a series of sporadic RTT patients, including an affected male, and to relate the genetic results to the clinical features of the disease, a clinical checklist and a score system were elaborated to evaluate the clinical severity of the disease. Mutation analysis of the MECP2 coding region was done by direct sequencing. De novo mutations were found in 60% of the patients, including both classic and atypical forms. The change R133H was identified in a 13-year-old boy showing a classic RTT phenotype and normal karyotype. Significant differences were observed among missense and truncating mutations regarding disease severity, age of onset of stereotypies, and the ability of the patients to sit alone and to walk.

Adolescent↗

PubMed2001

Congenital disorders of glycosylation (CDG) may be underdiagnosed when mimicking mitochondrial disease.

Congenital disorders of glycosylation (CDG) and mitochondrial diseases are multisystem disorders with clinical characteristics that may overlap. We present four patients with CDG whose phenotypes suggested the diagnosis of a mitochondrial disease. Patients 1 and 2 are siblings with hemiplegic headache, stroke-like episodes, lactic acidaemia and history of maternal migraine; their initial clinical diagnosis was MELAS syndrome (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes). Patient 3 suffers from ataxia, neuropathy, ophtalmoplegia and retinitis pigmentosa suggestive of NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. Patient 4 presented with neurological regression mimicking Leigh disease, with ptosis, myoclonus, ataxia and brainstem and cerebellar atrophy. Screening for mitochondrial disease including enzyme and mtDNA investigations on muscle biopsy were performed on Patients 1, 2 and 4 with normal results. However, evidence for a glycosylation disorder was substantiated by an increased carbohydrate deficient transferrin (CDT). The isoelectric focussing pattern of serum sialotransferrin was typical of CDG type I in Patients 1, 2 and 3 and was shifted towards the less sialylated bands in case 4. A deficiency of phosphomanomutase (PMM) confirmed the diagnosis of CDG-Ia in Patients 1, 2 and 3, who are compound heterozygous for mutations R141H/T237M (Patients 1 and 2) and R141H/P113L (Patient 3). In Patient 4, PMM activity was normal, and further enzymatic and molecular studies are underway. As the search for the primary defect in mitochondrial diseases is often unsuccessful, the pool of mitochondrial patients that remain without definite diagnosis might include CDG cases. Routine screening for CDG may avoid precocious invasive investigations.

Acidosis, Lactic↗

PubMed2001

A household food inventory for North American Chinese.

OBJECTIVE: To determine whether a short set of questions about foods in the household can provide information about the fat-related dietary behaviour of individual household members in less-acculturated Chinese populations. DESIGN: Cross-sectional survey. PARTICIPANTS: The study population included 244 adult females of Chinese ethnicity in Seattle, WA, and Vancouver, BC, Canada. SETTING: Bilingual interviewers collected information on the presence of 14 high-fat foods and seven reduced-fat foods in the household. Respondents were also asked about the consumption of foods and behaviour reflective of adoption of Western dietary practices, fat-related dietary behaviour, changes in consumption of high-fat foods since immigration, and sociodemographic characteristics. RESULTS: Although this was a less-acculturated sample, many households had Western foods such as butter (58%), lunchmeats (36%), snack chips (43%), and 1% or skim milk (48%). Households with respondents who were younger, married, employed outside the home, and lived with young children had significantly more high-fat foods, while high education and longer percentage of life in North America were significantly associated with having more reduced-fat foods (P , or = 0.05). Participants living in households with more high-fat foods had higher-fat dietary behaviour than those with fewer high-fat foods (fat-related dietary behaviour score, 1.54 versus 1.28; P < 0.001). Women in households with more reduced-fat foods had a significantly decreased consumption of high-fat foods since immigration compared with those in households with fewer reduced-fat foods (P < 0.001). Western dietary acculturation was higher among women in households both with more high-fat foods and more reduced-fat food counterparts (P < or = 0.05). CONCLUSIONS: Our inventory of household foods was strongly associated with current dietary behaviour, changes in food consumption, and westernization of dietary patterns. This simple, practical measure may be a useful alternative dietary assessment tool in less-acculturated Chinese populations.

Acculturation↗

PubMed2001

Urea is a product of ureidoglycolate degradation in chickpea. Purification and characterization of the ureidoglycolate urea-lyase.

A ureidoglycolate-degrading activity was analyzed in different organs of chickpea (Cicer arietinum). Activity was detected in all the tissues analyzed, but highest levels of specific activity were found in pods, from which it has been purified and characterized. This is the first ureidoglycolate-degrading activity that has been purified to homogeneity from any photosynthetic organism. Only one ureidoglycolate-degrading activity was found during the purification. The enzyme was purified 1,500-fold, and specific activity for the pure enzyme was 8.6 units mg(-1), which corresponds with a turnover number of 1,600 min(-1). The native enzyme has a molecular mass of 180 kD and consists of six identical or similar-sized subunits of 31 kD each. The enzyme exhibited hyperbolic, Michaelian kinetics for (-) ureidoglycolate with K(m) values of 6 and 10 microM in the presence or absence of Mn(2+), respectively. Optimum pH was between 7 and 8 and maximum activity was found at temperatures above 70 degrees C, the enzyme being extremely stable and resistant to heat denaturation. The activity was inhibited by EDTA and enhanced by several bivalent cations, thus suggesting that the enzyme is a metalloprotein. This enzyme has been characterized as a ureidoglycolate urea-lyase (EC 4.3.2.3), which catalyzes the degradation of (-) ureidoglycolate to glyoxylate and urea. This is the first time that such an activity is detected in plant tissues. A possible function for this activity and its implications in the context of nitrogen mobilization in legume plants is also discussed.

Amidine-Lyases↗

PubMed2000

Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis.

3-phosphoglycerate dehydrogenase (PHGDH) deficiency is a disorder of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures. To investigate the molecular basis for this disorder, the PHGDH mRNA sequence was characterized, and six patients from four families were analyzed for sequence variations. Five patients from three different families were homozygous for a single nucleotide substitution predicted to change valine at position 490 to methionine. The sixth patient was homozygous for a valine to methionine substitution at position 425; both mutations are located in the carboxyterminal part of PHGDH. In vitro expression of these mutant proteins resulted in significant reduction of PHGDH enzyme activities. RNA-blot analysis indicated abundant expression of PHGDH in adult and fetal brain tissue. Taken together with the severe neurological impairment in our patients, the data presented in this paper suggest an important role for PHGDH activity and L-serine biosynthesis in the metabolism, development, and function of the central nervous system.

Amino Acid Metabolism, Inborn Errors↗

PubMed2000

Allantoate amidinohydrolase (Allantoicase) from Chlamydomonas reinhardtii: its purification and catalytic and molecular characterization.

An allantoate-degrading enzyme has been purified to electrophoretic homogeneity for the first time from a photosynthetic organism, the unicellular green algae Chlamydomonas reinhardtii. The purification procedure included a differential protein extraction followed by conventional steps such as ammonium sulfate fractionation, gel filtration, anion exchange chromatography, and preparative electrophoresis. Under the routine assay conditions (7 mM allantoate), specific activity for the purified enzyme was 185 U/mg, which rose to 225 U/mg under kinetic considerations (saturating substrate). Therefore, a turnover number of 4.5 x 10(4) min(-1) can be deduced for the 200-kDa protein. The enzyme is a true allantoicase (EC 3.5.3.4) that catalyzes the degradation of allantoate to (-)ureidoglycolate and (+)ureidoglycolate to glyoxylate. The enzyme exhibited hyperbolic kinetic for allantoate and ureidoglycolate with K(m) values of 2 and 0.7 mM, respectively. V(max) of the reaction with allantoate as substrate was nine times higher than that with ureidoglycolate. The native enzyme has a molecular weight of 200 kDa and consists of six identical or similar-sized subunits of 34 kDa each, organized in two trimers of 100 kDa. Each subunit has five cysteine residues, four of which are involved in disulfide bonds, with a total of 12 disulfide bonds in the 200-kDa protein. Allantoate inhibits competitively the reaction with ureidoglycolate as substrate. In addition, buffers and group-specific reagents affect the activity in the same manner irrespective of the substrate used. Those results suggest that both substrates use the same active site. The effect of group-specific reagents suggest that the amino acids histidine, tyrosine, and cysteine are essentials for the allantoicase activity with both substrates.

Amino Acids↗

PubMed2000

Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI).

Lysinuric protein intolerance (LPI; MIM 222700) is an autosomal recessive disorder characterized by defective transport of the cationic amino acids lysine, arginine and ornithine at the basolateral membrane of the polar epithelial cells in the intestine and renal tubules, and by hyperammonemia after high-protein meals. LPI is caused by mutations in the SLC7A7 (solute carrier family 7, member 7) gene encoding y(+)LAT-1 (y(+)L amino acid transporter-1), which co-induces together with 4F2 heavy chain (4F2hc) system y(+)L in Xenopus oocytes. All Finnish LPI patients share the same founder mutation 1181-2A-->T (LPI(Fin)) not found in LPI patients elsewhere. Mutation screening of 20 non-Finnish LPI patients revealed 10 novel mutations: four deletions, two missense mutations, two nonsense mutations, a splice site mutation and a tandem duplication. Five LPI mutations (L334R, G54V, 1291delCTTT, 1548delC and LPI(Fin)) were studied functionally. All mutant proteins failed to co-induce amino acid transport activity when expressed with 4F2hc in Xenopus oocytes. Immunostaining experiments revealed that frameshift mutants 1291delCTTT, 1548delC and LPI(Fin)remained intracellular on expression with 4F2hc. In contrast, the missense mutants L334R and G54V reached the oocyte plasma membrane when co-expressed with 4F2hc, demonstrating that they are transport-inactivating mutations. This finding, together with the strong degree of conservation among all members of this family of amino acid transporters, indicates that residues L334 and G54 play a crucial role in the function of the y(+)LAT-1 transporter.

Amino Acid Metabolism, Inborn Errors↗

PubMed2000

Oxygen consumption measurement in lymphocytes for the diagnosis of pediatric patients with oxidative phosphorylation diseases.

OBJECTIVES: To evaluate the results of oxygen consumption measurement in lymphocytes for the diagnosis and treatment monitoring of pediatric patients with oxidative phosphorylation diseases. DESIGN AND METHODS: Twenty-four children with an oxidative phosphorylation disease were studied. Results were compared with those of 87 healthy children. Oxygen consumption measurements in digitonine-permeabilized lymphocytes incubated with pyruvate plus malate and succinate were performed in a Clark-type oxygen electrode. RESULTS: A total of 58% of patients showed a decreased oxygen consumption in lymphocytes incubated with pyruvate. In 4 patients, this analysis was the unique initial biochemical test, which revealed an impaired mitochondrial energy metabolism. Significant differences were observed in lymphocytes incubated with pyruvate between patients and reference values (p<0.00005), and in lymphocytes incubated with pyruvate before and after treatment (p<0.05). CONCLUSIONS: This test is useful for diagnosing oxidative phosphorylation diseases in patients who did not have other biochemical alterations, although false-negative results can be found. It is not useful for treatment monitoring.

Adolescent↗

PubMed2000

Mutation analysis of 16S rRNA in patients with Rett syndrome.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder that affects one in 10,000-15,000 females. RTT is mainly sporadic; familial cases have an estimated frequency of less than 1%. Before the recent identification of de novo dominant mutations in the X-linked MECP2 gene, many other hypotheses had been proposed to explain the particular pattern of inheritance and the phenotypic expression of the disease. The involvement of mitochondrial DNA had been investigated because of the structural and functional mitochondrial abnormalities evident in the patients. In 1997 the finding of mutations at 16S rRNA in several affected RTT females and their mothers was reported, suggesting that mitochondrial DNA might play a key role in the pathogenesis of RTT. To investigate the relevance of such mutations, we used the same methodologic approach to analyze RTT mitochondrial DNA in our series. No 16S rRNA alterations were evident in 27 Spanish patients with classic RTT.

Adolescent↗

PubMed2000

3-phosphoglycerate dehydrogenase deficiency in a patient with West syndrome.

3-phosphoglycerate dehydrogenase deficiency is a severe but treatable disorder of serine synthesis, first described in 1996 (Jaeken et al. 1996a). The patient presented with West syndrome, severe psychomotor delay, failure to thrive, microcephaly, atypical ocular movements, and pyramidal signs. Treatment with oral L-serine abolished seizures and improved psychomotor development, hyperexcitability, head growth, cortical and subcortical hypotrophy, and hypomyelination of the brain on MRI scans. 3-phosphoglycerate dehydrogenase deficiency is a treatable congenital error that probably leads to West syndrome.

Brain↗

PubMed2000

Knowledge and opinions about organ donation among urban high school students: pilot test of a health education program.

BACKGROUND: Increasing the diversity of the organ donor pool might improve the opportunities for people of color on organ transplant waiting lists to receive donated organs. We report on the results of a pilot classroom health education program to improve knowledge about organ donation and transplantation among a diverse student body at an urban high school. METHODS: The effectiveness of the educational program was evaluated with baseline and follow-up questionnaires which examined: 1) whether the program increased knowledge about organ donation; 2) whether the students' opinions about organ donation changed; and 3) whether the program was related to any changes in opinion. RESULTS: On the follow-up questionnaire, correct answers on 15 factual questions increased by 18% for the treatment group, compared to 5% for the control group (p = 0.00). Regarding opinions, at baseline 92% of white students had positive opinions about donation, compared to 48% of the students of color (p = 0.00). In the follow-up survey, the increase in positive opinions among the students of color was significantly greater than among white students (p = 0.04). In this pilot study, however, changes in opinions occurred with equal frequency among students in the treatment and control groups. In regression analysis, both knowledge of the subject and discussing donation with one's family were significantly associated with positive opinions about donation. CONCLUSIONS: Overall, this pilot study provided encouraging evidence that the classroom health education program affected knowledge about organ donation, and that opinions about organ donation are responsive to increases in knowledge.

Adolescent↗

PubMed2000

Anti-epileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C-->T mutation of the methylenetetrahydrofolate reductase gene.

The aim of the study was to observe the influence of carbamazepine and valproic acid on plasma total homocysteine and B-vitamin status and the gene-drug interaction with the 677C-->T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Plasma total homocysteine concentrations were determined in 136 epileptic children taking anti-epileptic drugs as monotherapy. Nutritional (folate, B12 and B6 vitamins) and genetic (MTHFR 677 C-->T) determinants of plasma homocysteine were studied in a random sample of 59 of the 136 epileptic children. Total homocysteine concentrations were significantly increased (p < 0.05) and folate and vitamin B6 levels were significantly decreased (p < 0.01) in the children taking anti-epileptic drugs compared with our reference ranges. In the carbamazepine-treated group, significantly positive correlation was found between duration of treatment and homocysteine concentration (p < 0.01). Homocysteine concentrations showed a significantly negative correlation with vitamin levels (folate: p = 0.002, and vitamin B12: p = 0.017) only in the carbamazepine treated group. In children treated with carbamazepine up to 3 years, total homocysteine concentration correlated negatively only with folate (p = 0.003), while in patients treated for more than 3 years, total homocysteine correlated negatively only with vitamin B12 values (p = 0.007). The lowering action of carbamazepine treatment on folate levels seems to be associated with hyperhomocysteinaemia, which seems to be related to the homozygous condition for the MTHFR 677C-->T mutation. Valproic acid treatment, although also associated with hyperhomocysteinaemia, only shows a lowering effect on vitamin B6 levels, which seems to be independent of the MTHFR genotype.

Adolescent↗

PubMed2000

Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate dehydrogenase deficiency.

White matter abnormalities are a feature of many inborn errors of metabolism and magnetic resonance imaging (MRI) of the brain has become an important tool in the diagnostic work-up of these disorders. Recently, patients were reported with a potentially treatable disorder of serine biosynthesis. They presented with congenital microcephaly, severe psychomotor retardation and intractable seizures. Low concentrations of the amino acids serine, glycine as well as 5-methyltetrahydrofolate were found in plasma and CSF and were due to a deficiency of the enzyme 3-phosphoglycerate dehydrogenase (3-PGDH). We studied four patients aged 10 months to 7 years by MRI before and after treatment with amino acids with a follow-up of 16 months to 6 years. Magnetic resonance spectroscopy (MRS) was performed in two patients at 4 and 16 months of treatment. Pre-treatment MRI demonstrated hypomyelination and profound white matter attenuation in all patients. During treatment, a significant increase in white matter volume was found and a progress of myelination in two patients. The most striking finding on MRS during treatment was an elevated level of white matter choline. Serine biosynthesis defects have to be considered in the differential diagnosis of patients with mental retardation, microcephaly, seizures, and on MRI hypomyelination and white matter attenuation.

Amino Acids↗

PubMed2000

Hepatitis B knowledge among Vietnamese immigrants: implications for prevention of hepatocellular carcinoma.

BACKGROUND: Vietnamese have higher liver cancer rates than any other racial/ethnic group in the United States. Approximately 80% of liver cancers are etiologically associated with hepatitis B virus (HBV) infection, which is endemic in Southeast Asia. METHODS: A telephone survey of randomly selected Vietnamese households (n = 75) was conducted during 1998 to examine HBV knowledge among Seattle's Vietnamese community. The questionnaire included items related to the transmission of HBV, the possible sequelae of infection, and disease prevention. RESULTS: The response rate was 70% among reachable and eligible households. Prior to being provided with a description of the disease, two thirds of our respondents had heard of HBV infection. Less than 60% knew that asymptomatic individuals can transmit the disease to others. Most thought that HBV infection can cause liver cancer (63%) and death (80%). However, only a minority knew that infection can be lifelong (38%) and incurable (22%). Finally, 28% had never heard of the HBV vaccine. There were significant associations between knowledge and educational level as well as home ownership. CONCLUSIONS: The findings suggest that Vietnamese immigrants have low levels of knowledge about HBV infection, and indicate a need for targeted educational interventions aimed at reducing HBV-related liver cancer mortality.

Adult↗

PubMed2000

Diagnostic approach to inborn errors of metabolism in an emergency unit.

OBJECTIVES: Our aim was to review the patients with a final diagnosis of inborn error of metabolism (IEM) who had previously required clinical attention at the emergency unit of our hospital over the last 9 years. METHODS: From the 184 patients with IEM, we selected 53 patients who required clinical attention at the EU as a prior step that led to a definitive diagnosis. We analyzed the frequency of the various IEM, their clinical presentations, and basic biochemical abnormalities in decompensation. RESULTS: We detected a predominance of neurologic signs (in 85% of our patients), followed by digestive symptoms (58.5%). Both were associated in 51% of patients. Vomiting and other digestive signs were observed in the same proportion as described in other series, but dehydration was only seen in three of our patients, probably because of early attention and fluid correction. CONCLUSIONS: 1) the diagnosis of an IEM has often been made after the first consultation at the EU, leading to hospitalization; 2) we should suspect an IEM in patients with neurologic abnormalities (eg, developmental delay, hypotonus or feeding difficulties), especially in those patients with multisystem involvement who appear with acute symptoms; 3) it is of the greatest importance that the appropriate sample collection be made before starting any treatment, because abnormal biochemical data can yield a first approach and allow the definitive diagnosis; and 4) the diagnosis of a patient with an IEM is not based on a single clinical or biochemical data but rather on all abnormal features taken together.

Emergency Service, Hospital↗

PubMed2000

Children with stroke: polymorphism of the MTHFR gene, mild hyperhomocysteinemia, and vitamin status.

The aim of this study was to investigate a possible association among the thermolabile polymorphism, nucleotide 677 cytosine to thymidine point mutation (677 C-->T) of the methylenetetrahydrofolate reductase (MTHFR) gene, hyperhomocysteinemia, serum folate, vitamins B12 and B6, and stroke in children. Allele and genotype frequencies for the 677 C-->T polymorphism in 21 children with stroke and 28 healthy children of the same age were studied. No differences in allelic frequency were detected between the two populations. However, the prevalence of homozygous 677 C-->T was doubled in the stroke population (28.6%) compared to the healthy group (14.3%). Total plasma homocysteine (tHcy) levels were significantly increased in children aged 2 months to 15 years with stroke compared to reference values. No association was observed between the homozygous genotype (T/T) and hyperhomocysteinemia, nor between the T/T genotype and low folate levels (below the 95th percentile) in this group of patients. Vitamin concentrations in patients were not significantly different from reference values. Significant negative correlations were found between tHcy and folate and between tHcy and cobalamin, but not between tHcy and B6 concentrations. In summary, a higher prevalence of hyperhomocysteinemia and the 677 C-->T polymorphism were observed in children with stroke, but were not always associated. The systematic study of both abnormalities in children with stroke is recommended, so that hyperhomocysteinemia of any genetic origin can be corrected with vitamin supplementation. Moreover, the 677 C-->T genotype is a strong factor for predisposition to hyperhomocysteinemia and recurrent risk of stroke that might also be prevented with folate supplementation.

Adolescent↗

PubMed2000

Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.

Glutaryl-CoA dehydrogenase (GCDH) deficiency causes glutaric aciduria type I (GA I), an inborn error of metabolism that is characterized clinically by dystonia and dyskinesia and pathologically by neural degeneration of the caudate and putamen. Studies of metabolite excretion allowed us to categorize 43 GA I Spanish patients into two groups: group 1 (26 patients), those presenting with high excretion of both glutarate and 3-hydroxyglutarate, and group 2 (17 patients), those who might not be detected by routine urine organic acid analysis because glutarate might be normal and 3-hydroxyglutarate only slightly higher than controls. Single-strand conformation polymorphism (SSCP) screening and sequence analysis of the 11 exons and the corresponding intron boundaries of the GCDH gene allowed us to identify 13 novel and 10 previously described mutations. The most frequent mutations in group 1 were A293T and R402W with an allele frequency of 30% and 28%, respectively. These two mutations were also found in group 2, but always in heterozygosity, in particular in combination with mutations V400M or R227P. Interestingly, mutations V400M and R227P were only found in group 2, and at least one of these mutations was found in 11 of 15 unrelated alleles, accounting together for 53% of the mutant alleles in group 2. Therefore, it seems clear that two genetically and biochemically distinct groups of patients exist. The severity of the clinical phenotype seems to be closely linked to the development of encephalopathic crises rather than to residual enzyme activity or genotype. Comparison of GCDH protein with other acyl-CoA dehydrogenases (whose x-ray crystal structure has been determined) reveals that most of the mutations identified in GCDH protein seem to affect folding and tetramerization, as has been described for a number of mutations affecting mitochondrial beta-oxidation acyl-CoA dehydrogenases.

Alleles↗