Hiperparatiroidisme 1 Pengkajian Identitas klien yang meliputi nama,alamat,umur,jenis kelamin,dannstatus 2. Riwayat Penyakit Sekarang mulai kapan tanda dan gejala muncul, jika ada nyeri bagaimana karakteristik nyerinya, penyebarannya, upaya yang sudah dilakukan untuk mengatasi penyakitnya. Riwayat Kesehatan Terdahulu adakah penyakit hipertensi, riwayat penyakit diabetes melitus, hipertiroid, hipotiroid, penyakit jantung. Pengobatan yang telah diberikan, serta pembedahan yang pernah dialami. Tanda-tanda Vital b.
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Neurogenetics of Pelizaeus-Merzbacher disease. Pelizaeus-Merzbacher disease PMD is an X-linked disorder caused by mutations in the PLP1 gene, which encodes the proteolipid protein of myelinating oligodendroglia.
PMD exhibits phenotypic variability that reflects its considerable genotypic heterogeneity, but all forms of the disease result in central hypomyelination associated with early neurologic dysfunction, progressive deterioration, and ultimately death. Two other less severe phenotypes were subsequently described, including the spastic paraplegia syndrome and PLP1-null disease. These disorders may be associated with duplications, as well as with point, missense, and null mutations within the PLP1 gene.
No effective therapy for PMD exists. Yet, as a relatively pure central nervous system hypomyelinating disorder, with limited involvement of the peripheral nervous system and little attendant neuronal pathology, PMD is an attractive therapeutic target for neural stem cell and glial progenitor cell transplantation, efforts at which are now underway in a number of centers internationally.
All rights reserved. Pelizaeus-Merzbacher disease PMD is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein PLP gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Magnetic resonance imaging in Pelizaeus-Merzbacher disease. Pelizaeus-Merzbacher 's disease is a progressive encephalopathy with demyelination of the cerebral white matter.
The diagnosis cannot be made on clinical or biological grounds: pathological investigation is necessary to confirm tigroid demyelination. CT scanning failure to visualize this type of anomaly but detection is now possible with the advent of magnetic resonance imaging MRI. The authors studied the case of a boy who, at the age of 8 presented with symptoms characeristic of the disease , rotatory nystagmus, progressive encephalopathy, and inherited X-linked recessive traits.
Magnetic resonance imaging revealed a high signal in the supra-tentorial white matter and the usual contrast was inverted. The authors believe that MRI can make an important contribution to the diagnosis of the disease. Genetics Home Reference: Pelizaeus-Merzbacher disease. Individuals with connatal Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease. Pelizaeus-Merzbacher disease PMD is a rare dysmyelinating disorder characterised by early pendular nystagmus, often rotatory and muscular hypotonia with subsequent ataxia, spasticity and mental retardation.
Autosomal recessive inheritance, particularly in the connatal form, cannot be excluded. Three different forms of the disease have been identified based on their onset, progression and severity of myelin pathology indicated by MRI features. Materials and methods. Our patients showed a markedly decreased peak of Cho. This alteration is well represented by quantitative analysis of the NAA-to-Cho ratio, which is the most important ratio affected.
A significant decrease of the Cho-to-Cr ratio is also present. In the connatal form of PMD, global lack of myelination may be relevant, as demonstrated by a significant Cho peak reduction.
Proton MR spectroscopy may be of diagnostic value in metabolic and destructive disorders of the brain. A greater number of patients with connatal PMD is needed in order to elucidate the significance of reduction of the Cho peak.
Magnetic resonance in Pelizaeus Merzbacher disease : findings in three brothers presenting the connatal variant. Pelizaeus Merzbacher disease is a rare hereditary disorder of the white matter that is characterized by nystagmic eye movements, head shaking and severe psychomotor retardation.
We report the MR findings in three brothers presenting the connatal variant of the disease , which is characterized by a diffuse increase in signal intensity on T2-weighted sequences, involving the white matter of the CNS. Author 10 refs. Directory of Open Access Journals Sweden. Full Text Available Pelizaeus-Merzbacher disease PMD is neurodegenerative leukodystrophy caused by dysfunction of the proteolipid protein 1 PLP1 gene on Xq22, which codes for an essential myelin protein.
As an X-linked condition, PMD primarily affects males; however there have been a small number of affected females reported in the medical literature with a variety of different mutations in this gene. No affected females to date have a deletion like our patient. In addition to this, our patient has skewed X chromosome inactivation which adds to her presentation as her unaffected mother also carries the mutation. Therapy of Pelizaeus-Merzbacher disease in mice by feeding a cholesterol-enriched diet.
Duplication of PLP1 proteolipid protein gene 1 and the subsequent overexpression of the myelin protein PLP also known as DM20 in oligodendrocytes is the most frequent cause of Pelizaeus-Merzbacher disease PMD , a fatal leukodystrophy without therapeutic options. PLP binds cholesterol and is contained within membrane lipid raft microdomains.
Cholesterol availability is the rate-limiting factor of central nervous system myelin synthesis. Transgenic mice with extra copies of the Plp1 gene are accurate models of PMD. Dysmyelination followed by demyelination, secondary inflammation and axon damage contribute to the severe motor impairment in these mice.
Here we show that cholesterol itself promotes normal PLP trafficking and that dietary cholesterol influences PMD pathology. In a preclinical trial, PMD mice were fed a cholesterol-enriched diet. This restored oligodendrocyte numbers and ameliorated intracellular PLP accumulation. Moreover, myelin content increased, inflammation and gliosis were reduced and motor defects improved. Even after onset of clinical symptoms, cholesterol treatment prevented disease progression.
Dietary cholesterol did not reduce Plp1 overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD. Pelizaeus Merzbacher disease PMD is an X-linked recessive disorder of the central nervous system myelination caused by mutations involving the proteolipid protein gene PLP.
Early nystagmus and developmental delay, progressive pyramidal, cerebellar and dystonic signs as well as white matter changes in brain MRI are typical for PMD. The PLP gene can be affected by two major types of mutations. A duplication of the whole PLP gene is the most common mutation and results usually in the milder classical phenotype, whereas point mutations in PLP gene often result in the rarer and more severe connatal form of PMD. The PLP protein is a higly conserved across species and is identical in human, mouse and rat.
We describe a year-old Czech boy with an early and severe developmental delay. His maternal uncle died at the age of one year and was also early and severely psychomotoricly retarded. The patient was the first child of healthy unrelated parents born after an uneventful pregnancy and delivery in Hyperbilirubinemia and bronchopneumonia and early stridor complicated his neonatal period. Diffuse hypotonia, nystagmus, psychomotor retardation, visual and hearing impairment have been observed in the patient since the age of 6 weeks.
White matter abnormalities, cortical and periventricular atrophy were detected by MRI at the age of 6 and 11 years, respectively. Despite these signs and results an accurate clinical diagnosis was unclear until the age of 11 years. Last neurological examination in showed no nystagmus anymore, but extremely dystrophic limbs, truncal deformation, due to severe scoliosis, tetraplegia with hyperreflexia in C5C7 and areflexia L2S2 and positive pyramidal signs.
The boy had no visual or speech contact. Although PLP1 proteins with missense mutations have been shown to accumulate in the rough endoplasmic reticulum ER in disease model animals and cell lines transfected with mutant PLP1 genes, the exact pathogenetic mechanism of PMD has not previously been clarified. Moreover, electron microscopic analysis demonstrated drastically reduced myelin formation accompanied by abnormal ER morphology.
Thus, this study demonstrates the involvement of ER stress in pathogenic dysmyelination in the oligodendrocytes of PMD patients with the PLP1 missense mutation. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement.
To the best of our knowledge this is the first time that this novel mutation HP of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients.
In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI, an ether lipid plasmalogen precursor. Full Text Available Abstract Background Childhood peroxisomal disorders and leukodystrophies are devastating diseases characterized by dysfunctional lipid metabolism. Plasmalogens ether glycerophosphoethanolamine lipids are decreased in these genetic disorders.
The biosynthesis of plasmalogens is initiated in peroxisomes but completed in the endoplasmic reticulum. We therefore undertook a study to evaluate the ability of a 3-substituted, 1-alkyl, 2-acyl glyceryl ether lipid PPI to replace plasmalogens in rhizomelic chrondrodysplasia punctata type 1 RCDP1 and rhizomelic chrondrodysplasia punctata type 2 RCDP2 lymphocytes which possess peroxisomal mutations culminating in deficient plasmalogen synthesis.
We also examined plasmalogen synthesis in Pelizaeus-Merzbacher disease PMD lymphocytes which possess a proteolipid protein-1 PLP1 missense mutation that results in abnormal PLP1 folding and it's accumulation in the endoplasmic reticulum ER, the cellular site of the last steps in plasmalogen synthesis. In vivo incorporation of plasmalogen precursor into tissue plasmalogens was also evaluated in the Pex7 mouse model of plasmalogen deficiency.
Metabolic conversion of PPI to the target plasmalogen was most active in the liver. Conclusions Our data demonstrate that PPI is activated. Attempts to identify a common pathogenic process underlying PMD have been complicated by an incomplete understanding of PLP1 dysfunction and limited access to primary human oligodendrocytes.
To address this, we generated panels of human induced pluripotent stem cells hiPSCs and hi These observations enabled classification of PMD subgroups by cell-intrinsic phenotypes and identified a subset of mutations for targeted More broadly, this study demonstrates the versatility of a hiPSC-based panel spanning the mutational heterogeneity within a single disease and establishes a widely applicable platform for genotype-phenotype correlation and drug screening in any human myelin Full Text Available Introduction.
Pelizaeus-Merzbacher disease PMD is an X-linked recessive hypomyelinating leukodystrophy characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. It is caused by mutation in the PLP1 gene. Case Description. We report a 9-year-old boy referred for oligoarray comparative genomic hybridization OA-CGH because of intellectual delay, seizures, microcephaly, nystagmus, and spastic paraplegia. Similar clinical findings were reported in his older brother and maternal uncle.
Both parents had normal phenotypes. Clinical presentation has been accepted as being the mainstay of diagnosis for most conditions. However, recent developments in genetic diagnosis have shown that, in many congenital and sporadic disorders lacking specific phenotypic manifestations, a genotype-to-phenotype approach can be conclusive. In this case, a diagnosis was reached by universal genomic testing, namely, whole genomic array. Genetics Home Reference: Pelizaeus-Merzbacher -like disease type 1.
By middle age, seizures become even less frequent. In addition to What is precision medicine? What is newborn screening?