Aleitamento materno em crianças com Síndrome de Down / Breastfeeding in infants with Down Syndrome

Objetivo ­ Avaliar as práticas de aleitamento materno em crianças com Síndrome de Down. O aleitamento materno é uma prática es-sencial para o desenvolvimento do hábito alimentar dos lactentes. O público que possui Síndrome de Down precisa de um auxílio nesse momento devido às características decorrentes da alteração genética que podem influenciar negativamente a prática. Métodos ­ Estudo transversal, com questionário direcionado a mães de crianças com Síndrome de Down participantes de grupos fe-chados de Síndrome de Down na rede social Facebook®, onde foram coletadas características socioeconômicas destas mulheres, além de características de sua gestação e informações pertinentes a crianças. Resultados ­ Observou-se que 44,0% tiveram dificuldade no aleitamento materno, e quase a metade das mães não conseguiram realizar o aleitamento materno exclusivo e a introdução alimentar de forma oportuna. Destaca-se, ainda, que 33,3% crianças receberam fórmula infantil e 30,5crianças leite de vaca. Conclusão ­ Diante deste cenário, é necessário que exista um acompanhamento dos profissionais da saúde durante a infância de indivíduos com Síndrome de Down, para que o desmame não ocorra precocemente.

Objective ­ To evaluate breastfeeding practices in children with Down syndrome. Breastfeeding is an essential practice for the development of infants eating habits. The public that has Down Syndrome needs help at this time due to the characteristics resulting from the genetic alteration that can negatively influence the practice. Methods ­ Cross-sectional study, questionnaire directed to mothers of children with Down Syndrome participating in closed groups of Down Syndrome on the social network Facebook®, where socioeconomic characteristics of these women were collected, as well as characteristics of their pregnancy and information relevant to the children. Results ­ It was observed that 44,0% had difficulties in breastfeeding, and almost half of the mothers were unable to perform exclusive breastfeeding and the introduction of food in a timely manner. It is also noteworthy that 33,3% children received an infant family and 30,5 children received cow's milk. Conclusion ­ Given this scenario, it is necessary that there is a monitoring of health professionals during childhood of obligation with Down Syndrome, so that weaning does not occur early.

Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

A family with early onset myopathy caused by MEGF10 gene defect and literature review / 中华儿科杂志

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.

Clinical and genetic analyses of Joubert syndrome in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical and genetic features of Joubert syndrome (JS) in children.@*METHODS@#A retrospective analysis was performed on the clinical data, genetic data, and follow-up data of 20 children who were diagnosed with JS in the Department of Children's Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, from January 2017 to July 2022.@*RESULTS@#Among the 20 children with JS, there were 11 boys and 9 girls. The common clinical manifestations were developmental delay (20 children, 100%), abnormal eye movement (19 children, 95%), and hypotonia (16 children, 80%), followed by abnormal respiratory rhythm in 5 children (25%) and unusual facies (including prominent forehead, low-set ears, and triangular mouth) in 3 children (15%), and no limb deformity was observed. All 20 children (100%) had the typical "molar tooth sign" and "midline cleft syndrome" on head images, and 6 children (30%) had abnormal eye examination results. Genetic testing was performed on 7 children and revealed 6 pathogenic genes, i.e., the CPLANE1, RPGRIP1L, MKS1, CC2D2A, CEP120, and AHI1 genes.@*CONCLUSIONS@#For children with developmental delay, especially those with abnormal eye movement and hypotonia, it is recommended to perform a head imaging examination to determine the presence or absence of "molar tooth sign" and "midline cleft syndrome", so as to screen for JS to avoid missed diagnosis and misdiagnosis. There are many pathogenic genes for JS, and whole-exome sequencing can assist in the diagnosis of JS.

Genetic analysis of a child with D bifunctional protein deficiency born to a consanguineous pedigree / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a child with D bifunctional protein deficiency (DBPD) born to a consanguineous pedigree.@*METHODS@#A child with DBPD who was admitted to the First Affiliated Hospital of Hainan Medical College on January 6, 2022 due to hypotonia and global developmental delay was selected as the study subject. Clinical data of her pedigree members were collected. Peripheral blood samples of the child, her parents and elder sisters were collected and subjected to whole exome sequencing. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 2-year-and-9-month-old female, had featured hypotonia, growth retardation, unstable head lift, and sensorineural deafness. Serum long-chain fatty acids were elevated, and auditory brainstem evoked potentials had failed to elicit V waves in both ears with 90 dBnHL stimulation. Brain MRI revealed thinning of corpus callosum and white matter hypoplasia. The child's parents were secondary cousins. Their elder daughter had a normal phenotype and no clinical symptoms related to DBPD. Elder son had frequent convulsions, hypotonia and feeding difficulties after birth, and had died one and a half month later. Genetic testing revealed that the child had harbored homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene, for which both of her parents and elder sisters were carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.483G>T (p.Gln161His) was rated as a pathogenic variant (PM1+PM2_Supporting+PP1+PP3+PP4).@*CONCLUSION@#The homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene caused by the consanguineous marriage probably underlay the DBPD in this child.

Clinical characteristics and genetic analysis of a child with Galactosemia due to compound heterozygous variants of GALT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis of a child with Galactosemia.@*METHODS@#A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing.@*RESULTS@#Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR).@*CONCLUSION@#Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.

Clinical characteristics of four children with 3M syndrome and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features of 3M syndrome and effect of growth hormone therapy.@*METHODS@#Clinical data of four children diagnosed with 3M syndrome by whole exome sequencing at Hunan Children's Hospital from January 2014 to February 2022 were retrospectively analyzed, which included clinical manifestation, results of genetic testing and recombinant human growth hormone (rhGH) therapy. A literature review was also carried our for Chinese patients with 3M syndrome.@*RESULTS@#The clinical manifestations of the 4 patients included severe growth retardation, facial dysmorphism and skeletal malformations. Two patients were found to harbor homozygous variants of CUL7 gene, namely c.4717C>T (p.R1573*) and c.967_993delinsCAGCTGG (p.S323Qfs*33). Two patients were found to harbor 3 heterozygous variants of the OBSL1 gene including c.1118G>A (p.W373*), c.458dupG (p.L154Pfs*1002) and c.690dupC (p.E231Rfs*23), among which c.967_993delinsCAGCTGG and c.1118G>A were unreported previously. Eighteen Chinese patients with 3M syndrome were identified through the literature review, including 11 cases (11/18, 61.1%) carrying CUL7 gene variants and 7 cases (7/18, 38.9%) carrying OBSL1 gene variants. The main clinical manifestations were in keeping with previously reported. Four patients were treated with growth hormone, 3 showed obvious growth acceleration, and no adverse reaction was noted.@*CONCLUSION@#3M syndrome has a typical appearance and obvious short stature. To attain accurate diagnosis, genetic testing should be recommended for children with a stature of less than -3 SD and facial dysmorphism. The long-term efficacy of growth hormone therapy for patients with 3M syndrome remains to be observed.

NEXMIF mutations in intellectual disability and epilepsy: A report of 2 cases and literature review / 中南大学学报(医学版)

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.

Analysis of a case with Xia-Gibbs syndrome due to variant of AHDC1 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of a child featuring Xia-Gibbs syndrome.@*METHODS@#Whole exome sequencing was carried out for the child.@*RESULTS@#The patient has presented with developmental delay, hypotonia, strabismus and snoring. Cranial MRI revealed hypomyelination, while the EEGs were normal. Genetic testing revealed a de novo variant of the AHDC1 gene, namely c.730delA (p.Ile244Serfs*16), which was classified as pathogenic (PVS1+PS2+PM2). Together with 60 cases from the literature, individuals harboring a AHDC1 variant commonly have delayed motor milestones, speech delay, facial dysmorphism and hypotonia. Dysgenesis of corpus callosum is also common. In total 47 AHDC1 variants have been reported, among which truncating variants were the most common type.@*CONCLUSION@#The c.730delA (p.Ile244Serfs*16) variant of the AHDC1 gene probably underlay the Xia-Gibbs syndrome in this patient. Above finding has provided a basis for the clinical diagnosis.

Analysis of 6 cases with hepatocerebral mitochondrial DNA depletion syndrome and literature review / 中华儿科杂志

Objective: To explore the clinical features of hepatocerebral mitochondrial DNA depletion syndrome (MDS). Methods: The clinical data of 6 hepatocerebral MDS patients diagnosed in the Jinshan Hospital of Fudan University from January 2012 to December 2019 were retrospectively collected and analyzed. Related literature published before January 2020 were searched with the key words of "DGUOK""MPV17""POLG""C10orf2" in PubMed, China national knowledge infrastructure (CNKI) and Wanfang database. Results: All the 6 hepatocerebral MDS cases were male. The age of onset ranged from 3 days to 8 months. The most common initial symptoms were cholestasis and developmental retrogression. The main clinical manifestations included hepatomegaly (4 cases), hypotonia (3 cases), growth retardation (4 cases), cholestasis (5 cases), coagulopathy (5 cases), hypoalbuminemia (3 cases), hypoglycemia (4 cases), hyperlactacidemia (5 cases), and abnormal blood metabolism screening (6 cases). The isotope hepatobiliary imaging revealed no gallbladder and intestinal tract development within 24 hours in 2 patients. Regarding the cranial imaging examination, the head CT found widening of the extracranial space in 1 case, the brain magnetic resonance imaging (MRI) found ventricular enlargement in 2 cases, and the brain ultrasound found peripheral white matter injury in 1 case. Two cases were lost to follow-up, one died of liver failure, and three died of multiple organ failure due to aggravated infection. Among the 6 cases, there were 3 with MPV17 variation (c.182T>C and c.279G>C were novel), 1 with POLG variation (c.2993G>A was novel), 1 with DGUOK variation (c.679G>A homozygous mutation, parthenogenetic diploid of chromosome 2) and 1 with C10orf2 variation (c.1186C>T and c.1504C>T were novel). The literature review found that 129, 100, 51 and 12 cases of hepatocerebral MDS were caused by DGUOK, MPV17, POLG and C10orf2 gene variations, respectively. And the most common clinical manifestations were liver dysfunction presented with cholestasis and elevated transaminase, metabolic disorders including hypoglycemia and hyperlactacidemia, and diverse neurologic symptoms including developmental retardation, hypotonia, epilepsy and peripheral neuropathy. Besides, 1/3 of the patients with C10orf2 variation developed renal tubular injury. Conclusions: Hepatocerebral MDS mainly present with liver dysfunction, metabolic disorder and neuromuscular impairment. Different genotypes show specific clinical manifestations.

Manejo anestésico y perioperatorio en paciente pediátrico con hiperglicinemia no cetósica / Anesthetic and perioperative management in children with non-ketotic hyperglycinemiawith non-ketotic hyperglycinemia

Presentación del caso: se reporta un paciente pediátrico con diagnóstico de hiperglicinemia no cetósica (HNC), enfermedad neurometabólica poco frecuente ocasionada por una deficiencia en el sistema de segmentación de la glicina, codificada por los genes GLDC, GCSH, AMT y GCSL que conduce a niveles elevados de glicina en la sinapsis generando un efecto agonista prolongado en los receptores N-metil-D-aspartato (NMDA). Discusión y conclusiones: se asocia con hipotonía, convulsiones y trastornos de la deglución, los cuales dependerán de la edad de presentación. Se revisa la literatura actual para el abordaje perioperatorio.

Case presentation: we report a child with a diagnosis of non-ketotic hyperglycinemia (NKGH), a rare neurometabolic disease caused by a defect in the glycine cleavage system, encoded by the GLDC, GCSH, AMT and GCSL genes resulting in elevated synaptic glycine levels generating a prolonged agonist effect on N-methyl-D-aspartate (NMDA) receptors. Discussion and conclusions: it is associated with hypotonia, seizures and swallowing disorders, which will depend on the age at presentation. A literature review was conducted to tailor perioperative approach.

Caracterización de la hipotonía-hiporrespuesta post vacuna pentavalente y tamizaje del neurodesarrollo en niños bajo 6 años de edad, 2013-2018, Uruguay / Characterization of hypotonia-hyporesponsiveness after pentavalent vaccine and neurodevelopmental screening in children under 6 years of age, 2013-2018, Uruguay

INTRODUCCIÓN: La hipotonía-hiporrespuesta (HHR) es uno de los efectos adversos supuestamente atribuibles a la vacunación e inmunización de tipo neurológico más notificados. El impacto a largo plazo a nivel del neurodesarrollo no es completamente conocida. OBJETIVO: Caracterizar los eventos de HHR post vacuna pentavalente notificados entre 2014 y 2018 al Ministerio de Salud Pública (MSP) de Uruguay. Realizar el tamizaje del neurodesarrollo de los que al momento de la evaluación tenían menos de 6 años de edad. METODOLOGÍA: Estudio descriptivo de las notificaciones al Sistema Nacional de Farmacovigilancia del MSP. Se realizó el tamizaje del neurodesarrollo con la Guía Nacional para la Vigilancia del Desarrollo. RESULTADOS: 30 casos, la mayoría de breve duración, en las primeras horas post primera dosis y con recuperación espontánea. Requirieron hospitalización 29. Se realizó el tamizaje del neurodesarrollo en 16. La media de tiempo entre el evento y esta evaluación fue 2 años y 2 meses. Fue normal la prueba de tamizaje en 15. En uno se detectó un retraso del lenguaje. CONCLUSIONES: Los episodios de HHR se presentaron con características similares a las descritas en la bibliografía. A pesar de las limitaciones del estudio, no se encontraron retrasos ni desvíos del desarrollo en los niños evaluados.

BACKGROUND: Hypotonic-hyporesponsive episodes (HHE) is one frequently reported neurologic adverse effect supposedly attributable to vaccination and immunization. Its long-term impact on neurodevelopment is not completely known. AIM: To characterize the post-pentavalent vaccine HHE events reported to the Uruguayan Ministry of Health (M of H) between 2014 and 2018. To perform neurodevelopment screening of those who were under 6 years of age at the time of evaluation. METHODS: Descriptive study of the reports made to the National Farmacosurveillance System of the M of H. Neurodevelopment screening was performed using the National Guidelines for Developmental Surveillance. RESULTS: 30 cases were studied. Most cases occurred after the first doses, were of short duration and during the first hours after vaccination, with spontaneous recovery. Median time between the event and this evaluation was 2 years and 2 months. Screening tests were normal in 15. Delay in the language area was detected in one case. CONCLUSIONS: HHE events had similar characteristics to those described in the literature, with no severe short-term complications. Despite the limitations of the present study, no delays nor deviations were found in the development of the children who were evaluated.

D-bifunctional protein deficiency caused by / 中国当代儿科杂志

A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the

Clinical and molecular genetic analysis of a patient with 3-M syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features and molecular genetic etiology of a patient with 3-M (Miller McKusick Malvaux) syndrome from a consanguineous parentage family, and to explore the relationship between genotype and phenotype.@*METHODS@#After the consent of the proband's guardian and the informed consent form was signed, DNA was extracted from peripheral blood samples of the proband and her parents for chromosome microarray analysis, medical exome sequencing and parental verification.@*RESULTS@#A total of 247.1 Mb loss of heterozygosity was found in the proband with a CytoScan 750K array. Furthermore, a homozygous variant (c.458dupG) of the OBSL1 gene was found using high-throughput sequencing, which was inherited from her parents. Based on the criteria and guidelines of genetic variation of American College of Medical Genetics and Genomics, the variant is predicted to be pathogenic (PVS1+PM2+PP4), and only one case was reported previously.@*CONCLUSION@#Spina bifida occulta and lower eyelid fat pad may be a special phenotype of c.458dupG variant of the OBSL1 gene. Our study may provide a useful reference for evaluating the relationship between genotype and phenotype of 3-M syndrome type 2.

Uso de canabidiol como terapia adjuvante em paciente com síndrome de Zellweger: relato de caso / Cannabidiol as adjuvant therapy in a patient with Zellweger syndrome: a case report

RESUMO: Também denominada síndrome cerebrohepatorenal, a síndrome de Zellweger é uma doença autossômica recessiva rara, pertencente ao espectro de erros inatos do metabolismo que afetam os peroxissomos. São causados principalmente por mutações em qualquer um dos 14 genes PEX diferentes que codificam para proteínas envolvidas na montagem do peroxissoma, sendo a mais comum do PEX1. O quadro clínico geralmente é observado no período neonatal e primeira infância, incluindo alterações faciais, hipotonia profunda e ausência de reflexos neonatais, além de disfagia, disfunção hepática e convulsões. O diagnóstico é feito a partir da clínica e testes bioquímicos e confirmados pela visualização da mutação em um dos 14 genes PEX. Como não há tratamento específico, é feito tratamento sintomático. Nosso paciente masculino de 1 ano e 9 meses apresentou a hipotonia congênita como sintoma marcante, além de crises convulsivas recorrentes logo após o nascimento. Evoluiu com necessidade de gastrostomia e estagnação de marcos neuromotores. O diagnóstico foi confirmado aos seis meses, através da dosagem de ácidos graxos de cadeia longa. Crises convulsivas evoluíram de maneira refratária a diversos anticonvulsivantes e com elevada frequência diária, por isso iniciamos canabidiol (CBD-RSHO GOLD) por via enteral que reduziu significantemente as crises. Não há tratamento definitivo para esta enfermidade, sendo importante tratamento sintomático das crises convulsivas e terapias de reabilitação, nesse caso, o uso de (CBD- RSHO GOLD) provocou uma redução de 92% na frequência de crises diárias do paciente. No entanto, não é possível concluir, ainda, melhoras em outros sinais e sintomas. (AU)

ABSTRACT: Also referred to as "brain-liver-kidney" syndrome, the Zellweger syndrome is a rare autosomal recessive disorder, belonging to the spectrum of inborn errors of metabolism that affect peroxisomes. They are caused mainly by mutations in any of the 14 different PEX genes that code for proteins involved in the assembly of peroxisome, being the most common of PEX1. The clinic is usually observed in the neonatal and early childhood period, including facial changes, deep hypotonia, and absence of neonatal reflexes in childhood, in addition to dysphagia, hepatic dysfunction, and seizures. The diagnosis is made from clinical and biochemical tests and confirmed by the visualization of the mutation in one of the 14 PEX genes. Since there is no specific treatment, symptomatic treatment is done. Our 1-year and 9-month-old male patient presented congenital hypotonia as a striking symptom in addition to recurrent seizures shortly after birth. It evolved with the need for gastrostomy and stagnation of neuromotor frames. The diagnosis was confirmed at six months by the measurement of long-chain fatty acids. Convulsive seizures evolved in a manner that was refractory to several anticonvulsants and with a high daily frequency, so we initiated cannabidiol (CBD-RSHO GOLD) by an enteral route that significantly reduced the seizures. Since there is no avail-able treatment for seizures, in this case, the use of CBD-RSHO GOLD reduced by 92% the daily seizure frequency. However, it is not possible to conclude further improvements in other signs and symptoms. (AU)

Clinical screening and genetic diagnosis for Prader-Willi syndrome / 中国当代儿科杂志

OBJECTIVE@#To study the clinical screening and genetic diagnosis of children suspected of Prader-Willi syndrome (PWS), as well as the differences in the scores of clinical diagnostic criteria among the children with a confirmed diagnosis of PWS.@*METHODS@#A total of 94 children suspected of PWS who were admitted from July 2016 to December 2018 were enrolled as subjects. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis. For the children with a confirmed diagnosis of PWS, the scores of clinical diagnostic criteria were determined, and the perinatal characteristics were analyzed.@*RESULTS@#A total of 11 children with PWS were confirmed by MS-MLPA, with a detection rate of 12%, among whom there were 7 boys and 4 girls, with a median age of 3 years and 4 months (range 25 days to 6 years and 8 months) at the time of confirmed diagnosis. Among the 11 children with PWS, only 5 children (45%) met the criteria for clinical diagnosis. The main perinatal characteristics of the children with PWS were decreased fetal movement (9 cases, 82%), cesarean section birth (11 cases, 100%), hypotonia (11 cases, 100%), feeding difficulties (11 cases, 100%), and weak crying (11 cases, 100%).@*CONCLUSIONS@#Gene testing should be performed as early as possible for children suspected of PWS by clinical screening. PWS may be missed if only based on the scores of clinical diagnostic criteria.

Professor 's clinical experience in treatment of syndrome with needling technique of acupuncture / 中国针灸

According to the effect of the spirit and in the treatment of syndrome and the theory as "acupoints of meridians especially for treatment of syndrome", professor - proposes the treatment principle of (regaining consciousness/spirit and promoting ). Guided by this treatment principle, the theory of traditional meridians and acupoints is coordinated with the achievement of modern medicine research. Consequently, needling technique of acupuncture is suggested. In the treatment of syndrome, the predominated prescriptions are formed for regaining consciousness/spirit, i.e. Baihui (GV 20), Sishencong (EX-HN 1), Fengfu (GV 16) and Fengchi (GB 20) and for promoting circulation, i.e. Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4) and Zusanli (ST 36). The acupoint prescriptions are modified align with the individual cases. This treatment regimen effectively relieves the symptoms and delayed the progress of disease.

Enfermedad de Pompe infantil: Diagnóstico y tratamiento / Infantile-onset Pompe disease: Diagnosis and management

La enfermedad de Pompe, o deficiencia de maltasa ácida o glucogenosis tipo II, es una grave enfermedad genética, autosómica recesiva, progresiva, poco frecuente, causada por la deficiencia en la enzima alfa glucosidasa. En la edad pediátrica, puede presentarse con la "forma clásica", la más conocida, con grave compromiso cardíaco y franca hipotonía, o con la "forma no clásica", con comienzo temprano del compromiso motor. La "forma de comienzo tardío" del adulto también puede ocurrir en la infancia o en la adolescencia. Se actualizan los hallazgos clínicos y de diagnóstico disponibles, ya que un tratamiento temprano con reemplazo de la enzima faltante puede mejorar la supervivencia y la calidad de vida del paciente. Se revisan los beneficios y los efectos adversos del tratamiento disponible y nuevas líneas de investigación terapéutica.

Pompe disease, also known as acid maltase deficiency or glycogenosis type II, is a rare severe, autosomal, recessive, and progressive genetic disorder caused by deficiency in alpha-glucosidase. The classic infantile-onset is the most broadly known form of Pompe disease, which presents with severe heart involvement and clear hypotonia, while the non-classic presentation occurs with early motor involvement. Late-onset Pompe disease develops in adults, but it may also occur during childhood or adolescence. Here we update the available clinical and diagnostic findings because an early management with enzyme replacement therapy may improve patients' survival and quality of life. We also review the benefits and adverse effects of available treatments and new lines of therapeutic research.