Combined oxidative phosphorylation deficiency type 4: clinical features and TUFM gene mutation analysis / 中华神经科杂志

Objective:To investigate the clinical characteristics of patients with combined oxidative phosphorylation deficiency type 4 (COXPD4) related to TUFM gene variation, in order to improve clinicians′ understanding of the disease. Methods:A case of COXPD4 with cystic leukodystrophy admitted to the Children′s Hospital of Zhengzhou University in June 2021 was taken as the study subject, and her clinical characteristics and genetic testing results were retrospectively analyzed. The "combined oxidative phosphorylation deficiency type 4" " TUFM gene" "cystic leukodystrophy" "combined oxidative phosphorylation deficiency 4" "COXPD 4" " TUFM" and "cystic leukodystrophy" were used as keywords, and the documents on COXPD4 related to TUFM gene mutations were reviewed from Wanfang Data Knowledge Service Platform, CNKI, PubMed Document Database, and National Center for Biotechnology Information (NCBI) until August 2021. The COXPD4 patients that have been reported internationally were analyzed for clinical features and variant types. Results:The patient was a 2-month-old girl with clinical manifestations of delayed development and progressive aggravation, elevated lactic acid in serum and cerebrospinal fluid, and diffuse white matter dysplasia with multiple cystic lesions in cerebral magnetic resonance imaging (MRI). Whole exome sequencing showed TUFM gene complex heterozygous variants c.684_684+4delGGTGA and c.1105C>T, which had not been reported in the past. A total of 5 cases of COXPD4 were reported in 4 English literatures. Together with 1 case in this study, there were 4 cases with detailed clinical history data, including 1 male and 3 females. The clinical manifestations were severe early-onset lactic acidosis and developmental lag, and 3 cases were accompanied by progressive infantile encephalopathy. Among them, 3 cases underwent head MRI examination, all of which showed diffuse white matter signal with multiple cystic lesions, 2 cases with basal ganglia involvement and multiple cerebellar gyri deformity. Genetic test indicated different types of TUFM gene variation. Conclusions:COXPD4 is a rare hereditary mitochondrial disease. For cases with COXPD4 clinical and imaging features, TUFM gene mutations can be screened first.

Hematopoietic Stem Cell Transplantation for Children With Inborn Errors of Metabolism: Single Center Experience Over Two Decades

Objective: We present outcome data on hematopoietic stem cell transplantation (HSCT) in children with inborn errors of metabolism (IEM). Methods: We retrospectively analyzed data on children up to 18 years of age, diagnosed with IEM, who underwent HSCT between January, 2002 and December, 2020. Results: 24 children, (mucopolysaccharidosis – 13, Gaucher disease – 4, X-linked adrenoleukodystrophy – 4, metachromatic leukodystrophy – 2, Krabbe disease – 1) were included. Donors were matched family donors in 24%, matched unrelated donors in 34%, and haploidentical fathers in 42% of the transplants, with engraftment in 91% of children. Overall survival was 72% (55-100%) with a median followup of 76.5 (10-120 ) months, and progression-free survival of 68% (MPS-76%, X-ALD - 60%, Gaucher disease – 50%, and 100% in MLD and Krabbe disease). Conclusion: HSCT is an available curative option, and early age at HSCT prevents end-organ damage.

Leucodistrofia metacromática del adulto: reporte de caso / Adult-onset metachromatic leukodystrophy

RESUMEN INTRODUCCIÓN: La leucodistrofia metacromática (LDM) es una enfermedad poco frecuente que se caracteriza por desmielinización progresiva a nivel del sistema nervioso central y periférico. En la mayoría de los casos, es causada por una actividad deficiente de la enzima arilsulfatasa-A. Pertenece al grupo de las leucodistrofias, que son trastornos hereditarios de la sustancia blanca asociados con una variabilidad fenotípica y una heterogeneidad genética importante. El fenotipo de la LDM suele relacionarse con la edad de presentación, que puede variar desde la infancia hasta la adultez. Cuando se presenta en la edad adulta, puede debutar con manifestaciones neuropsiquiátricas, lo que lleva con frecuencia a diagnósticos erróneos. REPORTE DE CASO: Se presenta el caso de una paciente adulta que debutó con un cuadro clínico caracterizado por cambios comportamentales progresivos, con posterior inicio de manifestaciones clínicas motoras. El diagnóstico de LDM se sospechó a partir de la clínica y los hallazgos típicos en la resonancia magnética (RM) cerebral, y se confirmó con la detección de actividad deficiente de la arilsulfatasa-A (ARSA) y la secuenciación del gen ARSA que confirmó la mutación en estado homocigoto, compatible con este diagnóstico. DISCUSIÓN: Destacamos en este caso la importancia de la sospecha clínica, el reconocimiento temprano y el manejo multidisciplinario como factores pronósticos del curso de la enfermedad, ya que en la actualidad no hay tratamiento definitivo para la enfermedad.

ABSTRACT INTRODUCTION: Metachromatic leukodystrophy (MLD) is an infrequent disease characterized by progressive demyelination of the central and peripheral nervous system. In most cases, it is caused by deficient activity of arylsulfatase-A. It belongs to the group of leukodystrophies, which are inherited white matter disorders that can be associated with significant phenotypic variability and genetic heterogeneity. The phenotype in MLD is usually related to the age of onset, which can vary from childhood to adulthood. Adult-onset MLD can debut with neuropsychiatry symptoms, which can often lead to misdiagnosis. CASE REPORT: We report the case of an adult female patient who presented with progressive behavioral changes, followed by motor manifestations. MLD was initially suspected based on the clinical presentation and the characteristic findings on brain magnetic resonance imaging (MRI), with subsequent confirmation by detection of deficient arylsulfatase-A (ARSA) activity and ARSA gene sequencing, which demonstrated homozygosity, compatible with this diagnosis. DISCUSSION: We highlight the importance of clinical suspicion, early recognition and multidisciplinary management as a prognostic factor for the course of the disease, since there is currently no definitive treatment for the disease.

Enfermedades desmielinizantes: leucodistrofia metacromática y esclerosis múltiple, a propósito de un caso / Demyelinating diseases: metachromatic leukodystrophy and multiple sclerosis, a case study

RESUMEN Las enfermedades desmielinizantes son entidades poco frecuentes en la edad pediátrica; tal es el caso de la esclerosis múltiple y la leucodistrofia metacromática, en las cuales intervienen factores genéticos y ambientales, y ambas afectan diferentes estructuras del sistema nervioso central, los nervios, los músculos, otros órganos y el comportamiento del individuo. Son afecciones que tiene una evolución progresiva al deterioro neuromuscular: en poco tiempo el paciente entra en un estado neurovegetativo con pérdida de la conciencia, por lo que requieren de atención médica y de enfermería especializada. El propósito de este estudio es presentar un caso de leucodistrofia metacromática, haciendo referencia a su complejo diagnóstico diferencial con la esclerosis múltiple y la aplicación del proceso de enfermería. Paciente masculino de 6 años de edad con antecedentes con antecedentes de diversos episodios de infecciones respiratorias y atelectasias, así como estadía prolongada en unidades de cuidados intensivos. Otros síntomas fueron hipotonía muscular, ausencia de reflejos tendinosos y trastornos audiovisuales. A la edad de 6 años el paciente había perdido todo contacto con el medio, sufrió tetraparesia y frecuentes episodios de convulsiones tónicas. A pesar de los intensos tratamientos y seguimientos en diferentes consultas, falleció a los 6 años de edad por complicaciones respiratorias.

ABSTRACT Demyelinating diseases are infrequent entities in pediatric age; such is the case of metachromatic leukodystrophy and multiple sclerosis, in which genetic and environmental factors take action. both of them affect different structures of the central nervous system, nerves, muscles, organs and individual behavior. These affections have a progressive evolution of the neuromuscular deterioration: soon the patient enters a neurovegetative state with loss of consciousness. Therefore, medical attention and specialized nursing is required. The purpose of this study is to present a case of metachromatic leukodystrophy referring to its complex differential diagnosis with multiple sclerosis and nursing process application. A 6-year-old male patient with record of several respiratory infections and atelectasis, such as extended stay at the intensive care unit. Some other symptoms were muscle hypotonia, lack of tendinous reflexes, and audiovisual disorder. At the age of 6 the patient had lost all contact with the environment, suffered from tetra paresis and frequent tonic seizure episodes. Despite the intense treatments and the follow-ups in several medical consultations, the patient passed away at the age of 6 due to respiratory complications.

Spastic ataxia type 8 with a homozygous mutation of the NKX6-2 gene: a case report and literature review / 中华实用儿科临床杂志

NKX6-2 encodes a transcription factor involving the genesis and development of oligodendrocytes.Mutations in the NKX6-2 gene are related to a severe variant of hypomyelinating leukodystrophy, namely the NKX6-2-related spastic ataxia type 8 (SPAX8). As of March 24, 2020, there are 36 cases of SPAX8 involving 11 mutations of the NKX6-2 gene, which has not been reported in Chinese population.This article for the first time reported a 31-month-old Chinese boy diagnosed as SPAX8 caused by a novel mutation of the NKX6-2 gene at c. 234dup(p.Leu79Alafs*? ) admitted to the Department of Rehabilitation, Guangdong Women and Children Hospital in October 2019 retrospectively.He presented severe global psychomotor delay, spasticity, nystagmus, hearing impairment and trichiasis, ametropia of both eyes, and retinal degeneration of the right eye, which have not been reported in previous cases.His elder sister presented relevant manifestations, but did not perform the genetic testing.Through this case report and literature review, the genotype and phenotype of SPAX8 were expanded.

Clinical and genetic characteristics of adolescent and adult Krabbe disease / 中华神经科杂志

Objective:To investigate the clinical and genetic characteristics of patients with late-onset subtypes (adolescent or adult) of Krabbe disease.Methods:The clinical data of 7 patients with Krabbe disease admitted to Shanghai Jiao Tong University Affiliated Sixth People′s Hospital and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2006 to June 2021 were analyzed and Sanger sequencing of the galactosylceramidase (GALC) gene (NM_000153) and detection of the activity of GALC were conducted. A total of 61 cases of Krabbe disease reported in domestic literature were reviewed and summarized.Results:Among the 7 patients with Krabbe disease, there were 4 males and 3 females. All of them had lower limb weakness or walking difficulty as the initial symptoms, and presented as spastic paraplegia. The symptoms were relatively mild in patients with late onset. There were 4 out of 5 patients undergoing magnetic resonance imaging examination, who showed abnormal signals: 2 had brain atrophy and the remaining 2 had white matter lesions. A total of 5 GALC gene mutations were detected by genetic analysis. Among these, c.1901T>C (p.L634S), c.908C>T(p.S303F) and c.461C>A(p.P154H) are known variants, while c.50_51insTT (p.M17Ifs) and c.1130delT(p.L337X) are novel variants reported for the first time in this paper.Conclusions:Krabbe disease is a rare neurodegenerative disease with phenotypic heterogeneity, which is inherited in an autosomal recessive mode. The severity of clinical manifestations of Krabbe disease is correlated with the age of onset.

Research advances in the clinical genetics of leukodystrophy in children / 中国当代儿科杂志

Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous system disease in children and has significant genotype-phenotype correlation. In recent years, the improvement in high-throughput sequencing has changed the diagnostic and therapeutic mode of LD, and elaborative phenotype analysis, such as the collection of natural history and multimodal neuroimaging evaluation during development, also provides important information for subsequent genetic diagnosis. This article reviews LD from the perspective of clinical genetics, in order to improve the awareness of this disease among pediatricians in China.

Alanyl-transfer ribonucleic acid synthetase 2 gene mutation producing leukodystrophy: a case report / 中华神经科杂志

Objective:To investigate the clinical features, imaging features and gene mutation of a paitent with alanyl-transfer ribonucleic acid synthetase 2 (AARS2) gene mutation- related leukodystrophy and further improve the understanding of this rare disease.Methods:Clinical data of a patient with leukodystrophy associated with AARS2 gene mutation diagnosed in October 2020 at Xiamen Hospital of Beijing University of Chinese Medicine and Huashan Hospital of Fudan University were collected.Results:The male patient, 25 years old, was admitted with the clinical manifestations, including chronic onset dyskinesia, ataxia, nystagmus and psoriasis. Head magnetic resonance imaging (MRI) showed bilateral white matter lesions and cerebellar atrophy. Spine MRI showed vertebral body incomplete fusion. Gene detection showed heterozygous compound AARS2 gene mutation [c.985C>T chr6:44275041(p.R329C) and c.452T>C chr6:44279256(p.M151T)].Conclusions:AARS2 gene mutation-related leukodystrophy is a rare mitochondrial disease in clinical practice. The patient presented with progressive motor deficits in the lower limbs, ataxia, relatively retained cognitive function. MRI revealed abnormal symmetry of corpus callosum and bilateral paraventricular white matter. Heterozygous compound AARS2 gene mutations [c.985C>T chr6:44275041 (p.R329C) and c.452T>C chr6:44279256 (p.M151T)] are one of the pathogenic factors leading to hereditary leukodystrophy.

Case report of clinical features of 4H syndrome and analysis of POLR3A gene / 中华实用儿科临床杂志

Clinical data of a case of 4H syndrome admitted to the Department of Neurology, Anhui Children′s Hospital in January 2019 were retrospectively analyzed.The male patient with 2 years and 7 months old had clinical manifestations of motor and mental retardation, unstable gait, and abnormal tooth development.Head magnetic resonance imaging revealed abnormal brain white matter development.Family-wide exon detection revealed compound heterozygous mutations of the POLR3 A gene, c.3858C>A (exon29) and c. 3226G>A (exon24), which were newly detected pathogenic mutations.It is suggested that 4H syndrome should be considered in children with early developmental retardation, abnormal tooth development, and abnormal white matter.

Analysis of ARSA gene variant in an infant with late infantile metachromatic leukodystrophy / 中华医学遗传学杂志

Objective@#To detect pathogenic variant of ARSA gene in an infant with late infantile metachromatic leukodystrophy (MLD).@*Methods@#The male proband had an onset of walking dysfunction and seizure at 28 months. Arylsulfatase A activity of his peripheral blood leucocytes was 26.9 nmol/mg.17h, and cranial MRI showed wild symmetrical demyelination. With genomic DNA extracted from his peripheral blood sample, all coding exons and splicing sites of the ARSA gene were subjected to Sanger sequencing. PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. Ucsf chimera software was used to analyze the impact of candidate variants on the secondary structure of the protein product. Impact of potential variants was also analyzed with software including PolyPhen-2, Mutation Taster, SIFT and PROVEAN. Whole-exome sequencing was carried out to identify additional variants which may explain the patient’s condition.@*Results@#The proband was found to harbor compound heterozygous variants of the ARSA gene [c.467G>A (p.Gly156Asp) and c. 960G>A (p.Trp320*)], neither of which was reported previously. As predicted by Ucsf chimera software, the c. 960G>A (p.Trp320*) variant may demolish important secondary structures including α-helix, β-strand and coil of the ARSA protein, causing serious damage to its structure and loss of function. The c. 467G>A (p.Gly156Asp) variant was predicted to be "probably damaging" by PolyPhen-2, Mutation Taster and SIFT software.@*Conclusion@#The patient’s condition may be attributed to the compound heterozygous c. 467G>A (p.Gly156Asp) and c. 960G>A (p.Trp320*) variants of the ARSA gene. Above results have facilitated genetic counseling and prenatal diagnosis for this family.

Van der Knaap disease

Van der Knaap disease is a rare form of leukodystrophy, phenotypically characterized by megalencephaly, early-onset ataxia, pyramidal features, cognitive impairment, with an autosomal recessive inheritence. MRI Brain shows T1 and FLAIR hypointense subcortical cysts in mostly temporal lobes and in fronto-parietal subcortical areas. Authors report a 20 yr. girl with typical features.

Leucodistrofia metacromática infantil tardía: Presentación de un caso / Late infantile metachromatic leukodystrophy: case report

La leucodistrofia metacromática es una enfermedad autosómi-ca recesiva poco común ocasionada por el déficit de la enzima lisosomal arilsulfatasa A, el cual provoca una desmielinización progresiva con manifestaciones neurológicas subsecuentes. Dentro de sus formas de manifestación, la infantil tardía es la de peor pronóstico. La resonancia magnética juega un papel importante en la caracterización de anormalidades subyacentes, lo que permite descartar otras afecciones clínicas y aproximar un diagnóstico, que, posteriormente, es confirmado mediante los análisis moleculares apropiados. Dado el escaso conocimiento de esta enfermedad, sumado a un curso clínico generalmente fatal, se hace fundamental una identificación temprana y precisa con el fin de iniciar un manejo paliativo y asesoría genética. Se presenta a una paciente femenina de 24 meses de edad con historia de retardo psicomotor y hallazgos imagenológicos compatibles con leucodistrofia. Los estudios enzimáticos y moleculares confirmaron el diagnóstico de leu-codistrofia metacromática infantil tardía.

Metachromatic leukodystrophy is an uncommon autosomal recessive disease caused by the deficiency of the arylsulfatase A lysosomal enzyme, which causes a progressive demyelin-ation with subsequent neurological manifestations. Between its manifestation forms, the one presenting in late childhood has the worst prognosis. Magnetic resonance plays an important role in the characterization of underlying abnormalities, which makes it possible to rule out other clinical conditions and approximate a diagnosis that is later confirmed by the appropriate molecular studies. Given the limited knowledge of the condition, coupled with a generally fatal clinical course, an early and accurate identification is fundamental in order to start palliative management and genetic counseling. A 24 months old female patient with psychomotor retardation history and imaging findings compatible with leukodystrophy is presented. Enzymatic and molecular studies confirmed a diagnosis of late childhood metachromatic leukodystrophy.

Clinical and aspartoacylase gene mutation analysis of Canavan disease in a child / 中华神经科杂志

Objective To investigate the clinical and aspartoacylase (ASPA) gene mutation characteristics of Canavan disease.Methods The clinical data of a child with Canavan disease diagnosed by gene detection who visited Children's Hospital Affiliated to Zhengzhou University in June 2018 were reviewed and analyzed.Results A one year and five months old girl presented with psychomotor retrogression,hypermyotonia,and tendon hyperreflexia.The urinary N-acetylaspartic acid levels were significantly higher (66.832 7,more than 60 times that of normal individuals).Magnetic resonance imaging of the brain showed a multiple and symmetrical hyperintense signal changes in the cerebral white matter.Two heterozygous mutations c.79_80del (p.Gly27Arg) and c.554G＞T (p.Gly185Val) were screened by targeted next generation sequencing.The results of Sanger sequencing showed the two mutations were compound heterozygous mutation derived from her father and mother,and the mutation c.554G＞T has never been reported.Conclusions The next generation sequencing can accurately detect ASPA gene mutation as the first choice for the diagnosis of Canavan disease.The mutation c.554G＞T enriches the gene mutation spectrum of Canavan disease.

Late Infantile-Onset Globoid Cell Leukodystrophy: Treatment using Hematopoietic Stem Cell Transplantation / 대한소아신경학회지

Globoid cell leukodystrophy is a rare autosomal recessive disorder of the brain white-matter caused by galactosylceramidase deficiency; the disorder is classified into four types based on the age of onset. Approximately 80–85% of patients have an early infantile form, while 10–15% has a late infantile form. Globoid cell leukodystrophy leads to a progressive neurological deterioration, and affected patients rarely survive more than 2–3 years. Although many different treatments have been investigated over several decades, further research is still needed. Hematopoietic stem cell transplantation is the standard treatment for globoid cell leukodystrophy. Here, we report a case of symptomatic late-infantile globoid cell leukodystrophy treated with stem cell transplantation. After transplantation, disease progression ceased and cognitive and motor function improved. And a 6 months follow-up study using brain magnetic resonance imaging showed white matter involvement was increased. After that, annual follow-up brain magnetic resonance imaging showed a stable status of disease.

Metachromatic leukodystrophy / 国际儿科学杂志

Metachromatic leukodystrophy is an inherited lysosomal disorder caused by autosomal reces-sive mutations of ARSA gene or PASP gene,which result in the accumulation of sulfatides in the central and pe-ripheral nervous system leading to demyelination. The disease is classified into a late-infantile,juvenile and adult onset type based on the age of onset,all characterized by a variety of neurological symptoms,which eventually lead to death if untreated. There is no curative treatment for all types and stages. This review discusses pathogen-esis,clinical manifestations,diagnostic process and efficacy of current and possible future therapies such as en-zyme replacement therapy,hematopoietic stem cell transplantation and gene therapy. A longer follow up period for the above therapies are needed to come to a general conclusion and improve treatment options for metachro-matic leukodystrophy.

Identification of a novel mutation in ARSA gene in three patients of an Iranian family with metachromatic leukodystrophy disorder

Abstract Metachromatic leukodystrophy disorder (MLD) is an autosomal recessive and lysosomal storage disease. The disease is caused by the deficiency of the enzyme arylsulfatase A (ARSA) which is encoded by the ARSA gene. Different mutations have been reported in different populations. The present study was aimed to detect the mutation type of the ARSA gene in three relative Iranian patients. We found a novel homozygous missense mutation c.1070 G > T (p.Gly357Val) in exon 6 of these patients. The mutation was found to be reported for the first time in MLD patients. The data can update the mutation profile and contribute toward improved clinical management and counseling of MLD patients.

Asociación entre la mutación homocigota c.318A>T en el exón 2 del gen EIF2B5 y la forma infantil de la leucoencefalopatía con sustancia blanca evanescente / Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy

Resumen: Introducción: La leucoencefalopatía con sustancia blanca evanescente es una de las leucodistrofias más frecuentes. Generalmente inicia en la infancia y presenta un patrón de herencia autosómica recesiva. El 90% de los casos manifiesta mutaciones en uno de los genes que codifican para las cinco subunidades del factor de iniciación eucariótica 2 (EIF2B5). El diagnóstico se realiza por las manifestaciones clínicas, hallazgos en la resonancia magnética cerebral y estudios moleculares confirmatorios. Caso clínico: Paciente masculino de 13 meses con neurodesarrollo previo normal. Antecedente de internamiento por vómito, hipertermia, irritabilidad y rechazo a la vía oral de 15 días de evolución. Ante la exploración presentó perímetro cefálico y pares craneales normales. Se encontró hipotónico, con reflejos incrementados, sin datos meníngeos ni de cráneo hipertensivo. La tomografía de cráneo mostró hipodensidad generalizada de la sustancia blanca. Egresó sin recuperar deambulación. A los 15 días presentó somnolencia y crisis convulsivas focales después de traumatismo craneoencefálico. En la resonancia magnética se observó hipointensidad generalizada de sustancia blanca. Ante la sospecha de leucoencefalopatía con sustancia blanca evanescente, se solicitó la secuenciación del gen EIF2B5, que reportó mutación homocigota c.318A>T en el exón 2. El paciente requirió múltiples hospitalizaciones por hipertermia y descontrol de crisis convulsivas. Posteriormente mostró deterioro cognitivo, motor y pérdida de la agudeza visual. Falleció a los 6 años por neumonía severa. Conclusiones: Este caso contribuye a conocer el espectro de mutaciones que se presenta en pacientes mexicanos y permite ampliar el fenotipo asociado con esta mutación.

Abstract: Background: Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with an autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be accomplished by the clinical and neuroradiological findings and molecular tests. Case report: We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia and irritability. On examination, cephalic perimeter and cranial pairs were normal. Hypotonia, increased muscle stretching reflexes, generalized white matter hypodensity on cranial tomography were found. Fifteen days after discharge, he suffered minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized hypointensity of white matter. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. Conclusions: This case contributes to the knowledge of the mutational spectrum present in Mexican patients and allows to extend the phenotype associated to this mutation.

¿Tiene el paciente una leucodistrofia? Importancia de la descripción clínica, la semiología y las neuroimágenes ante la sospecha diagnóstica de leucodistrofia de origen metabólico / Does the patient have a leukodystrophy? Importance of clinical description, semiotics and neuroimaging in the diagnostic suspicion of a metabolicorigin leukodystrophy / O paciente tem uma leucodistrofia? Importância da descrição clínica, a semiótica e as neuroimagens ante a suspeita diagnóstica de leucodistrofia de origem metabólica

RESUMEN El enfoque de los errores innatos del metabolismo (EIM) constituye un desafío para cualquier especialidad médica y es un área en rápido desarrollo; a medida que se amplía la información científica, se fortalece el estudio de las enfermedades metabólicas y crecen la necesidad y el interés de hacer diagnósticos certeros y oportunos, de manera que sea posible comenzar el tratamiento apropiado lo más pronto posible. Es preciso usar un enfoque sistemático y ordenado que incluya todas las entidades clínicamente parecidas, desde las más frecuentes hasta las más raras, usando racionalmente los estudios más especializados y complejos, que, en general, son menos accesibles para el paciente. Presentamos el caso de una paciente con historia de noxa perinatal y alteraciones neurológicas cuyo curso clínico no progresó. Se resalta la importancia de un proceso diagnóstico sistemático que le dé prioridad al cuadro clínico.

SUMMARY The approach to inborn errors of metabolism (IEM) is a challenge for any medical specialty. This is a rapidly developing area. As scientific information expands, the study of metabolic diseases strengthens, and increases the need and interest in confirming or discarding such errors, in order to offer patients prompt and appropriate therapeutic alternatives. To achieve this, it is necessary to use a rational and orderly clinical approach that takes into account the possibility of an IEM, as well as other diseases resembling them. Also to rationalize the use of more specialized, and complex diagnostic aids, that generally are less accessible to the patient. We report the case of a patient with a history of perinatal noxa, and neurological disorders, whose clinical course did not progress. The importance of a systematic diagnostic process, based mainly on the clinical picture, is emphasized.

RESUMO A focagem dos erros inatos do metabolismo (EIM) constitui um desafio para qualquer especialidade médica e é uma área em rápido desenvolvimento; na medida que amplia-se a informação científica, fortalece-se o estudo das doenças metabólicas e crescem a necessidade e o interesse de fazer diagnósticos certeiros e oportunos, de maneira que seja possível começar o tratamento apropriado o mais rápido possível. É preciso usar uma focagem sistemática e ordenada que inclua todas as entidades clinicamente parecidas, desde as mais frequentes até as mais raras, usando racionalmente os estudos mais especializados e complexos, que, em geral, são menos acessíveis para o paciente. Apresentamos o caso de uma paciente com história de noxa perinatal e alterações neurológicas cujo curso clínico não avançou. Ressalta-se a importância de um processo diagnóstico sistemático que de prioridade ao quadro clínico.

Metachromatic leukodystrophy. Case presentation / Leucodistrofia metacromática. Presentación de caso

ABSTRACT Metachromatic leukodystrophy (MLD) is a rare demyelinating disease (prevalence 1:40,000), also called arylsulfatase A deficiency (ARS-A), which may present with neurological and psychiatric symptoms. Clinical assessment may be difficult, due to unspecific signs and symptoms. A case is presented of a 16 year-old female patient seen in psychiatry due to behavioural changes, psychosis, and with impaired overall performance. She was ini tially diagnosed with schizophrenia, but the Nuclear Magnetic Resonance (NMR) scan and laboratory tests lead to the diagnosis of MLD.

RESUMEN La leucodistofia metacromática (LDM) es una enfermedad desmielinizante rara (prevalencia, 1:40.000), también llamada deficiencia de arilsulfatasa A (ARS-A), que puede presentarse con síntomas neurológicos y psiquiátricos y cuyo diagnóstico puede plantear dificultades para el clínico, dado lo inespecífico de los signos y síntomas. Se presenta el caso de una paciente de 16 arios atendida por psiquiatría por cambios conductuales, psicosis y deterioro general del funcionamiento. Inicialmente diagnosticada como esquizofrenia, se documentaron por resonancia magnética y pruebas de laboratorio en la evolución cambios que llevaron al diagnóstico de leucodistrofia metacromática.