RESUMEN
The hot spot mutation P291fsinsC was identified for the first time in a 26 years old Tunisian woman. The low serum level of high C-reactive protein was helpful to target the HNF1A gene. Due to the molecular diagnosis, the change from insulin to sulfonylurea therapy was performed successfully.
Asunto(s)
ADN/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factor Nuclear 1-alfa del Hepatocito/genética , Insulina/administración & dosificación , Mutación , Compuestos de Sulfonilurea/administración & dosificación , Administración Oral , Adolescente , Adulto , Análisis Mutacional de ADN , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Inyecciones Intramusculares , Masculino , Linaje , TúnezRESUMEN
Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is characterized by an accumulation of sulfatides in the central and peripheral nervous system. It is due to the enzyme deficiency of the sulfatide sulfatase i.e. arylsulfatase A (ASA). we studied 5/200 cases of MLD and clearly distinguished three clinical forms. One of them presented the juvenile form; two presented the late infantile form; and two other presented the adult form. The Magnetic Resonance Imaging (MRI) of these patients showed a diffuse, bilateral and symmetrical demyelination. The biochemical diagnosis of MLD patients evidencing the low activity of ASA and sulfatide accumulation. PATIENTS AND METHODS: We studied 5/200 MLD patients addressed to us for behavioral abnormalities and progressive mental deterioration. All of them were diagnosed at first by brain MRI evidencing a bilateral demyelination, then the measurement of ASA activity using P-nitrocathecol sulfate as substrate, finally the sulfatiduria was performed using thin-layer chromatography using alpha-naphtol reagent. RESULTS: In this study, from 200 patients presenting behavioral abnormalities and a progressive mental deterioration, we reported just 2 patients were diagnosed as late-infantile form of MLD. Only1 case presented as the juvenile form; and 2 patients with the adult-type of MLD. The brain magnetic resonance imaging (MRI) of all patients showed characteristic lesions of MLD with extensive demyelination. Biochemical investigations of these patients detected a low level of ASA activity at 0°C and 37°C; the excess of sulfatide in sulfatiduria. CONCLUSION: MRI is required to orient the diagnosis of MLD patients; the latter must be confirmed by the biochemical investigations which is based on the measurement of ASA activity and the excess of sulfatide showed in the sulfatiduria. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1791578262610232.
Asunto(s)
Encéfalo/patología , Leucodistrofia Metacromática/patología , Imagen por Resonancia Magnética , Adulto , Biomarcadores/orina , Encéfalo/enzimología , Catecoles/metabolismo , Cerebrósido Sulfatasa/deficiencia , Preescolar , Cromatografía en Capa Delgada , Femenino , Humanos , Leucodistrofia Metacromática/clasificación , Leucodistrofia Metacromática/enzimología , Leucodistrofia Metacromática/psicología , Masculino , Trastornos Mentales/etiología , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Sulfoglicoesfingolípidos/orina , Túnez , UrinálisisRESUMEN
We present an update of knowledge on diabetes MODY (maturity onset diabetes of the young), including the recent molecular discoveries, and new diagnostic strategies. Considerable progress has been made in understanding the different molecular abnormalities that cause MODY and the phenotypic consequences resulting therefrom. MODY diabetes is very heterogeneous and is the most common form of monogenic diabetes. Its distribution is worldwide. MODY is an autosomal dominant diabetes mellitus, nonketotic and occurs at an early age (usually before 25 years). To date, at least seven genes are associated with MODY, with frequencies that differ from one population to another. Both 2 and 3 subtypes predominate, while other subtypes (1, 4, 5, 6 and 7) concern only a few families. Since its discovery in the sixties, studies have succeeded to fully clarify the epidemiological, molecular and clinical diagnosis of each subtype, to provide better care for patients. However, the subject of MODY has not yet revealed all its secrets. Indeed, it remains to identify other genes that are associated with MODY X.
Asunto(s)
Investigación Biomédica/tendencias , Diabetes Mellitus Tipo 2/etiología , Endocrinología/tendencias , Diabetes Mellitus Tipo 2/clasificación , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Endocrinología/métodos , Genotipo , Geografía , Humanos , Modelos Biológicos , Patología Molecular/tendencias , Fenotipo , Terminología como AsuntoRESUMEN
We recruited a 44-year-old woman who had a dementia with behavioral and personality troubles. A biochemical analysis which includes a qualitative study of urinary sulfatides by thin layer chromatography followed by the determination of the enzymatic activity of arylsulfatase A (ARSA) was performed. The Molecular analysis concerned the research of the most frequent mutations (459 +1 G> A, p.P426L, p.I179S). The profile that has revealed the presence of 3-O-sulfogalactosylceramide fraction was in favor of metachromatic leukodystrophy. The activity of arylsulfatase A was collapsed in the index case which confirmed the phenotype of the adult form of the diagnosed MLD. The molecular study showed the presence of the mutation p.I179S in the homozygous state in the index case.
Asunto(s)
Cerebrósido Sulfatasa/genética , Demencia/complicaciones , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/genética , Mutación , Adulto , Biomarcadores/metabolismo , Femenino , Humanos , Leucodistrofia Metacromática/enzimología , Fenotipo , TúnezRESUMEN
Scholz's disease or metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a deficiency in arylsulfatase A (ARSA: EC 3.1.6.8). This enzyme is responsible for the degradation of sulfatides commonly called cerebroside-3-sulfate or 3-O-sulfogalactosylcéramide in galactocérébroside and sulfate. The success of hydrolysis of these sphingolipids by ARSA necessarily depends on the presence of saposine B forms a complex with the substrate. The pathological accumulation of sulfatides in the nervous system (myelin, neurons and glial cells) results most often neurological, mental retardation, nervous disorders, blindness. The metachromatic granules accumulated in the central nervous system and peripheral compounds are highly toxic. These are at high levels in the urine of patients affected by the MLD. Arylsulfatase A activity is collapsed in these patients. Unfortunately, the value of enzyme activity is not a predictor of clinical severity of the neuropathology. In contrast, the study of the gene that codes for the ARSA is seen as a way to diagnose the simplest and most reliable of the disease to avoid misdiagnosis due to the presence of pseudodeficit. The conventional therapeutic approaches are essentially symptomatic. They were made in order to restore the enzyme activity of arylsulfatase A and prevent the progression of the pathological accumulation of sulfatides and consequently reduce morbidity associated with MLD.