Monthly, syndrome

monthly proficiENT in a disease, intensive reading a book a month, monthly familiar with a drug.

ward patiENTs admitted to a hyperthyroidism, a history of questioning patients a few years ago, one after another put a diabetes insipidus and diabetes.So, three endocrine and metabolic diseases are concentrated in a patient, whether monism can be used to explain?

, read the literature, nor can the three diseases linked.After the hyperthyroidism, diabetes is most certainly not hyperthyroidism caused by nor can the pituitary TSH tumor explained.

However, if diabetes insipidus and diabetes linked to, indeed can find some clues, but patiENTs with no hearing and vision abnormalities.

Nevertheless, I still think of a disease encountered by the residENT age: Wolfram syndrome.

Overview

Wolfram, syndrome DIDMOAD syndrome, also known as diabetes insipidus (diabetes insipidus), diabetes mellitus (diabetes), the optic atrophy (optic atrophy), deafness (deafness)], the case often autosomal recessive hereditary neurodegenerative diseases, in 1938 first reported by Wolfram.The incidence of the disease is about 1/100 000, their age of onset before age 20, but also with onset after the age of 40.

etiology and pathogenesis of

more research to learn about the cause of Wolfram syndrome, the majority of scholars believe that the disease is an autosomal recessive genetic disease, also can be distributed.Support the basis of genetic diseases are: (1) Panamonta sum up all over the world report over 100 cases of patiENT data, found that the disease mode of inheritance follows Mendelian autosomal recessive inheritance law .(2) The Karasik study shows that age of onset of a high consistency in the multiplex families.(3) from 1982 to 2002, many scholars have done with the patiENT's HLA haplotype analysis, inference DIDMOAD non-autoimmune-borne diseases.(4) the Karasik studies have shown that this syndrome in patients with pancreatic islet cell atrophy phenomenon, but the islet β-cell antibody in the blood.Swift, psychiatric symptoms of the syndrome (5) studies have shown that Wolfram syndrome gene as the causative gene the gene coding for 9-10 transmembrane protein (6 ) magnetic resonance imaging (MRI) evidence of: optic atrophy, MRI normal; genetic, MRI abnormalities.The optic nerve of this syndrome have abnormal MRI signal, and the degeneration associated with demyelination.Thus, more and more evidence that this syndrome is a genetic-related neurological degenerative disease.

Wolfram, syndrome abnormalities in patiENTs diagnosed as mitochondrial disease, especially chronic progressive extraocular muscle paralysis syndrome (CPEO) patients.These led to the following thinking : Wolfram, syndrome may be the joint presence of the potENTial of mitochondrial function obstacle.Mitochondrial dysfunction may be the result of nuclear genes or mitochondrial genetic abnormality.As necessary to maintain normal mitochondrial function proteins encoded by these two genes.The mode of inheritance can help us to distinguish the location of the defective gene.Nuclear gene mutation is in accordance with the Mendelian way down pass.Defects of the mitochondrial DNA is maternally inherited.However, many patients are distributing or recessive, the latter is inferred from the expression of the form of the disease between the brothers and sisters.However, this mode of inheritance among the brothers and sisters by the matriarchal way genetic.The correlation analysis of several Family studies have shown that: Wolfram syndrome defective gene is located 4P16.1 (WFS1).Another phenotype to chromosome 4q22-q24 of the second part of the defect (WFS2).Wolfram syndrome phenotype can be nonspecific and may reflect the many different types of nuclear genes or mitochondrial gene defects.

In recENT years, studies have shown that most of the Wolfram syndrome is WFS1 gene mutation in patients with heterozygous mutation in the homozygous or compound mutations, the former more than the intermarriage .WFS1 gene contains eight exons, encoding 890 amino acid protein composed of Wolfram, in.The protein expression of the broad, heart, brain and pancreas have a higher expression, its functional role is not clear, is a transmembrane protein, mainly presENT in the endoplasmic reticulum, membrane transport, protein processing and islet β-cell inhibition of apoptosis mechanisms.

Wolflam syndrome pathogenesis is not yet clear, may be multi-gene mutation.The past, the disease is caused by defects in mitochondrial genes, one of the most common tRNAleu (UUB) nt3243A → G point mutation, and later it was discovered that many patiENTs with Wolfram syndrome is not detected in the mitochondrial DNA mutation.Abnormal gene to the disease in 1998 - WFS1 was found, which is located to the short arm of chromosome No.4 (4pl6.1), another abnormal gene - WFS2 located in the long arm (4q22-24), are encoded wolframin (a transporter membrane glycoprotein).Research indicates that 90% of patients with Wolfram syndrome can be detected in a WFS variation, and therefore one of the diagnostic criteria for the WFS variation as Wolflam syndrome, but the diagnosis of the disease is still mainly relies on clinical indicators.Chromosomal genetic defects and (or) mitochondrial gene defect can cause Wolfram syndrome, some patients only WFS or mitochondrial genetic defects, some of the existing WFS variation, another mitochondrial gene defects, but did not find the WFS variation of mitochondrial gene defects between the existence of any association.

clinical performance

for type 1 diabetes, eye symptoms, deafness, diabetes insipidus

Wolfram, syndrome, there are four main symptoms: ( 1) type 1 diabetes: usually the first disease, multi-disease in childhood.for insulin-dependENT diabetes.( 2) ocular symptoms: more than 6 to 7-year-old began to vision loss, often 2 to 3 years after diagnosis in type 1 diabetes, 98% associated with optic atrophy.part may be associated with visual field defects, color blindness, retinitis pigmENTosa, nystagmus, an individual can also occur cataract.( 3) deafness: high-frequency-based, suggesting that nerve deafness, and its incidence is about 70%.( 4) diabetes insipidus: cENTral, occur in approximately 32%.(5) other performance: There are hydronephrosis, hydroureter, low tension and bladder.

In addition, Wolfram syndrome is also accompanied by other neurological and psychiatric manifestations, including ataxia, muscle spasm, neurogenic bladder, mania, depression, organic brain Zheng, etc..

Endocrine system may have pituitary dwarfism, hypothyroidism, sexual retardation and other symptoms.

digestive symptoms such as diarrhea or constipation.

diagnosis

mainly relies on clinical indicators.The diagnosis of Wolfram syndrome to clinical manifestations and clinical four kinds of performance are for the complete type, incomplete for incomplete form, the latter being more common.

scholars have pointed out, if the patiENT has diabetes, with Bilateral optic atrophy, the diagnosis can be established.

diagnosed rely on genetic testing.