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1.
J Diabetes Res ; 2014: 921616, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24719898

RESUMO

The rising incidence of diabetes and its negative impact on quality of life highlights the urgent need to develop biomarkers of early nerve damage. Measurement of total vitamin B12 has some limitations. We want to determine the levels of urinary methylmalonic acid and its relationships with serum vitamin B12 and polyneuropathy. The 176 Chinese patients with Type 2 diabetes mellitus were divided into 3 groups according to the levels of vitamin B12. A gas chromatography mass spectrometric technique was used to determine blood methylmalonic acid and urinary methylmalonic acid. The diagnosis of distal diabetic polyneuropathy was based on the determination of bilateral limb sensory and motor nerve conduction velocity and amplitude with electromyogram. Multiple regression analysis revealed that urinary methylmalonic acid/creatinine, blood methylmalonic acid, and so forth were variables that influenced diabetic polyneuropathy significantly. Nerve sensory conduction velocity and nerve amplitude in the group of urinary methylmalonic acid/creatinine >3.5 mmol/mol decreased significantly. Superficial peroneal nerve sensory and motor conduction velocity and ulnar nerve compound motor active potential amplitude were inversely correlated with urinary methylmalonic acid/creatinine. Urinary methylmalonic acid correlates with serum vitamin B12 levels in person with diabetes and is a sensitive marker of early polyneuropathy.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/complicações , Ácido Metilmalônico/urina , Polineuropatias/complicações , Deficiência de Vitamina B 12/complicações , Adulto , Idoso , Povo Asiático , Biomarcadores/sangue , Biomarcadores/urina , China , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/urina , Feminino , Humanos , Masculino , Ácido Metilmalônico/sangue , Pessoa de Meia-Idade , Neurônios Motores/metabolismo , Condução Nervosa , Polineuropatias/sangue , Polineuropatias/fisiopatologia , Polineuropatias/urina , Estudos Prospectivos , Células Receptoras Sensoriais/metabolismo , Índice de Gravidade de Doença , Vitamina B 12/sangue
2.
Orphanet J Rare Dis ; 7: 90, 2012 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-23181892

RESUMO

BACKGROUND: D-bifunctional protein (DBP) deficiency is typically apparent within the first month of life with most infants demonstrating hypotonia, psychomotor delay and seizures. Few children survive beyond two years of age. Among patients with prolonged survival all demonstrate severe gross motor delay, absent language development, and severe hearing and visual impairment. DBP contains three catalytically active domains; an N-terminal dehydrogenase, a central hydratase and a C-terminal sterol carrier protein-2-like domain. Three subtypes of the disease are identified based upon the domain affected; DBP type I results from a combined deficiency of dehydrogenase and hydratase activity; DBP type II from isolated hydratase deficiency and DBP type III from isolated dehydrogenase deficiency. Here we report two brothers (16½ and 14 years old) with DBP deficiency characterized by normal early childhood followed by sensorineural hearing loss, progressive cerebellar and sensory ataxia and subclinical retinitis pigmentosa. METHODS AND RESULTS: Biochemical analysis revealed normal levels of plasma VLCFA, phytanic acid and pristanic acid, and normal bile acids in urine; based on these results no diagnosis was made. Exome analysis was performed using the Agilent SureSelect 50Mb All Exon Kit and the Illumina HiSeq 2000 next-generation-sequencing (NGS) platform. Compound heterozygous mutations were identified by exome sequencing and confirmed by Sanger sequencing within the dehydrogenase domain (c.101C>T; p.Ala34Val) and hydratase domain (c.1547T>C; p.Ile516Thr) of the 17ß-hydroxysteroid dehydrogenase type 4 gene (HSD17B4). These mutations have been previously reported in patients with severe-forms of DBP deficiency, however each mutation was reported in combination with another mutation affecting the same domain. Subsequent studies in fibroblasts revealed normal VLCFA levels, normal C26:0 but reduced pristanic acid beta-oxidation activity. Both DBP hydratase and dehydrogenase activity were markedly decreased but detectable. CONCLUSIONS: We propose that the DBP phenotype seen in this family represents a distinct and novel subtype of DBP deficiency, which we have termed type IV based on the presence of a missense mutation in each of the domains of DBP resulting in markedly reduced but detectable hydratase and dehydrogenase activity of DBP. Given that the biochemical testing in plasma was normal in these patients, this is likely an underdiagnosed form of DBP deficiency.


Assuntos
17-Hidroxiesteroide Desidrogenases/deficiência , 17-Hidroxiesteroide Desidrogenases/genética , Hidroliases/deficiência , Hidroliases/genética , Ataxia Cerebelar/sangue , Ataxia Cerebelar/genética , Ataxia Cerebelar/urina , Ácidos Graxos/sangue , Ácidos Graxos/urina , Perda Auditiva Neurossensorial/sangue , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/urina , Heterozigoto , Mutação , Proteína Multifuncional do Peroxissomo-2 , Ácido Fitânico/sangue , Polineuropatias/sangue , Polineuropatias/genética , Polineuropatias/urina , Retinose Pigmentar/sangue , Retinose Pigmentar/genética , Retinose Pigmentar/urina
3.
J Neurol ; 255(7): 974-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18574620

RESUMO

Acute porphyrias are a group of inherited metabolic disorders representing overproduction syndromes with the formation of neurotoxic haem precursors. Clinical manifestations consist of acute attacks, which include abdominal pain, dysautonomia, mental symptoms, polyneuropathy and seizures mimicking many other acute neurological disorders.Porphyrin metabolites were screened in 108 patients with acute polyneuropathy or encephalopathy associated with pain and/or dysautonomia, who attended neurological wards, in order to evaluate the number of patients with acute porphyria.Urinary porphyrins and their precursors were increased in 21% of the cases. Surprisingly many patients (11%) had previously undiagnosed acute porphyria. Half of these patients had had mild to moderate symptoms of acute porphyria previously. Secondary porphyrinuria, which was mainly transient coproporphyrinuria because of hepatopathy, was also common (10%). Of the 108 patients studied, the levels of urinary porphyrins or their precursors were normal in the majority (79%) of the cases, who commonly had Guillain-Barré syndrome (40%). Epileptic seizures were also frequent (18%), but none of the patients with acute porphyria had solely epileptic seizures without prolonged confusion (>or= 1 day).Based on our findings, acute inherited porphyria is not infrequent among the selected group of neurological patients and screening of urinary PBG is cost-beneficial. Since the correct diagnosis of a hereditary disease is essential, genetic screening should be performed whenever possible for patients with clinically and biochemically confirmed acute porphyria.


Assuntos
Encefalopatias/diagnóstico , Encefalopatias/urina , Polineuropatias/diagnóstico , Polineuropatias/urina , Porfobilinogênio/urina , Adolescente , Adulto , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Prospectivos
4.
Free Radic Res ; 40(7): 723-9, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16983999

RESUMO

The objective of this study was to establish if diabetes in the presence of polyneuropathy (PN) and/or cardiovascular autonomic neuropathy (CAN) is associated with alterations in the amounts of 8-epi-PGF2alpha (IP) and its metabolites including 2, 3-dinor-8-epi-PGF2alpha (dinor-IP) and 2, 3-dinor-5, 6 dihydro-8-epi-PGF2alpha (dinor-dihydro-IP) in urine. Mass spectrometric separation showed that excretion of IP was similar in the PN + /CAN- and PN+/CAN+ groups but higher than in the PN-/CAN- group (n = 103, 22 and 60, respectively; P < 0.05). By contrast, excretion of dinor-IP or dinor-dihydro-IP were similar in the PN-/CAN- and PN+/CAN- groups but higher than in PN+/CAN+ group. Correlations were obtained between IP and dinor-IP or dinor-dihydro-IP (r = 0.30; P < 0.001 and r = 0.31; P < 0.001, respectively). A significant association was also observed between dinor-IP and dinor-dihydro-IP (r = 0.48; P < 0.001). In conclusion, these biomarkers should prove useful in studies evaluating the impact of therapeutic drugs or antioxidant interventions aimed at delaying the onset of diabetic complications.


Assuntos
Doenças Cardiovasculares/urina , Diabetes Mellitus/urina , Neuropatias Diabéticas/urina , Dinoprosta/análogos & derivados , F2-Isoprostanos/urina , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/urina , Dinoprosta/metabolismo , Dinoprosta/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Polineuropatias/etiologia , Polineuropatias/urina
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