Pelizaeus-Merzbacher Disease, Easily Misdiagnosed as Cerebral Palsy: A Report of a Three-generation Family

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder affecting myelination of the central nervous system, and is caused by mutations of the proteolipid protein 1 (PLP1) gene. Clinical manifestations of PMD are variable and major features include progressive nystagmus, spasticity, tremor, ataxia, and psychomotor delay. We describe a classical PMD patient who had been misdiagnosed as cerebral palsy. He had nystagmus and psychomotor delay since infancy and tremor with ataxia developing gradually. Brain MRI revealed demyelination over white matter of the cerebral hemispheres and posterior limbs of the internal capsules. Positive family history led to subsequent mutation analysis, which identified a novel mutation (c.88G>C) in PLP1 in the proband, as well as his affected brother and maternal uncle, and asymptomatic maternal grandmother, mother and two sisters. Therefore, PMD should be considered in a cerebral palsy-like patient with or without positive family history. Mutation analysis is crucial for early diagnosis and further genetic counseling

Outcomes at late childhood of Chinese-speaking preschoolers with developmental language disorders comorbid with behavioral-emotional

As part of an ongoing clinical service program for children with developmental delay in morphosyllabic Chinese-speaking Taiwan, we investigated the late childhood cognitive, functional and psychiatric outcomes of a specific cohort of preschool children with developmental language delay comorbi d wi th behavi oral-emoti onal problems. The institutional database of a developmental clinic was reviewed and preschoolers meeting the inclusion criteria were invited to be subjects. Follow-up evaluations included Wechsler Intelligence tests, parents’ version of the Child Behavioral Checklist and psychiatric interview of the adolescents themselves. Of the eligible subjects (initial preschool visit at average of 3.8 ± 1.3 years old), 44 individuals completed follow-up evaluations at average of 11.8 ± 1.5 years old. The follow-up results showed that 75% of the late childhood children still had problems in language and 38.6% had problems in academic performance. The mean nonverbal cognitive score at follow-up was 83.9 ± 15.4 while the mean verbal cognitive measure was 83 ±17.3. Total 75% of the subjects had current psychiatric disorders and the most frequent di agnosi s was attenti on defici t/hyperactivity disorder, which was noted to be increased from 50% in the preschool period to 70.5% in late childhood. We concluded that the majority of Chinese-speaking preschoolers with language delay and behavioral-emotional problems turned out to have communication and psychiatric conditions when they reached late childhood. Western researches on developmental course of preschool children with alphabetic language impairment could be extended to morphosyllabic Chinese. Specialized services are warranted for this group of preschool children to lessen prolonged vulnerabilities. Our findings may be helpful in the context of an Asian developing country, so that priorities can be established for the allocation of finite resources for intervention

Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif

<p>Abstract</p> <p>Background</p> <p>Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an autosomal recessive disease caused by the defects in the mitochondrial electron transfer system and the metabolism of fatty acids. Recently, mutations in electron transfer flavoprotein dehydrogenase (<it>ETFDH</it>) gene, encoding electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) have been reported to be the major causes of riboflavin-responsive MADD. To date, no studies have been performed to explore the functional impact of these mutations or their mechanism of disrupting enzyme activity.</p> <p>Results</p> <p>High resolution melting (HRM) analysis and sequencing of the entire <it>ETFDH </it>gene revealed a novel mutation (p.Phe128Ser) and the hotspot mutation (p.Ala84Thr) from a patient with MADD. According to the predicted 3D structure of ETF:QO, the two mutations are located within the flavin adenine dinucleotide (FAD) binding domain; however, the two residues do not have direct interactions with the FAD ligand. Using molecular dynamics (MD) simulations and normal mode analysis (NMA), we found that the p.Ala84Thr and p.Phe128Ser mutations are most likely to alter the protein structure near the FAD binding site as well as disrupt the stability of the FAD binding required for the activation of ETF:QO. Intriguingly, NMA revealed that several reported disease-causing mutations in the ETF:QO protein show highly correlated motions with the FAD-binding site.</p> <p>Conclusions</p> <p>Based on the present findings, we conclude that the changes made to the amino acids in ETF:QO are likely to influence the FAD-binding stability.</p

SMN類似基因的分析

[[abstract]]Part of a survivial motor neuron (SMN) gene-like DNA fragment has been identified .This DNA fragment was accidentally isolated from cDNA by RT–PCR using primers specific for the region between exon 3 and 6 of the SMN gene .This fragment was used as a probe to hybridize the mRNA from several tissues, but we have been unable to detect any transcript of this SMN-like gene in these tissues. Thus, we have inferred this SMN gene-like fragment was a genomic product contaminant that was amplified in the reaction . Sequencing analysis of this fragment , which contains several stop codons, revealed a 74.6% nucleotide homology with the SMN gene. From these results, we believe that this DNA fragment is not a mutated form of SMN gene . Rather , it is an SMN-like pseudogene ,which is variably present even in normal individuals.[[abstract]]我們利用RT–PCR方法分析SMN基因的表現，分析其產物偶然發現一段與SMN基因非常相似的產物，其DNA序列的分析結果顯示有74.6%的核?酸同質性，但其中含有幾個停止的密碼，我們又發現此基因片斷在各種組織並無表現，因此，我們認為它是一個SMN偽基因的片斷。此偽基因片斷並無intron，而且有些正常人並無此基因

Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy

Therapeutic hypothermia (TH) is a recommended regimen for newborn infants who are at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy (HIE). The Task Force of the Taiwan Child Neurology Society and the Taiwan Society of Neonatology held a joint meeting in 2015 to establish recommendations for using TH on newborn patients with HIE. Based on current evidence and experts' experiences, this review article summarizes the key points and recommendations regarding TH for newborns with HIE, including: (1) selection criteria for TH; (2) choices of method and equipment for TH; (3) TH prior to and during transport; (4) methods for temperature maintenance, monitoring, and rewarming; (5) systemic care of patients during TH, including the care of respiratory and cardiovascular systems, management of fluids, electrolytes, and nutrition, as well as sedation and drug metabolism; (6) monitoring and management of seizures; (7) neuroimaging, prognostic factors, and outcomes; and (8) adjuvant therapy for TH. Key Words: hypoxic ischemic encephalopathy, neonate, patient care, perinatal asphyxia, therapeutic hypothermi

Valproate-induced Hyperammonemic Encephalopathy

Valproate-induced hyperammonemic encephalopathy is an unusual but serious complication that can occur in people with normal liver-associated enzyme levels, and despite normal therapeutic doses and serum levels of valproate. Here, we describe an adolescent girl suffering from absence seizures, who complained of progressive dizziness and general malaise several days after restarting valproate. She developed vomiting and decreased consciousness after 3 weeks of valproate use. She had a serum ammonia level five times higher than the upper normal limit, normal liver-associated enzymes, and a supra-therapeutic valproate level. Electroencephalography (EEG) showed continuous generalized slowing. Tandem mass spectrometry analysis revealed carnitine deficiency. Her consciousness improved after emergent hemodialysis. Her ammonia level and EEG also became normal. Possible mechanisms, risk factors and treatments of valproate-induced hyperammonemic encephalopathy are described. Physicians should consider this possibility when consciousness disturbance occurs in patients treated with valproate