Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency / 中国当代儿科杂志

Phosphomannomutase 2 deficiency is the most common form of N-glycosylation disorders and is also known as phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). It is an autosomal recessive disease with multi-system involvements and is caused by mutations in the PMM2 gene (OMIM: 601785), with varying severities in individuals. At present, there is still no specific therapy for PMM2-CDG, and early identification, early diagnosis, and early treatment can effectively prolong the life span of pediatric patients. This article reviews the advances in the diagnosis and treatment of PMM2-CDG.

Characterization of the SRD5A3-CDG Clinical Spectrum

Abstract We aimed to characterize the clinical spectrum of patients diagnosed with SRD5A3-CDG, a subtype of congenital disorders of glycosylation (CDG) due to variants in the steroid 5a-reductase type 3 (SRD5A3) gene. It presents with multi-systemic involvement including neurological disability, dermatologic abnormalities, and ophthalmological defects. We conducted a cross-sectional study of children (n=6, ages 4-16 years) with a confirmed diagnosis of SRD5A3-CDG (c.57G>A, p.W19X). Families completed a detailed medical history questionnaire, two quality of life measures, and an adaptive behavior scale. Prevalent clinical features in our cohort included visual impairment (6/6), developmental delay (6/6), nystagmus (5/6), retinal dystrophy (4/6), and hypotonia (3/6). The Vineland Adaptive Behavior Scales demonstrated deficits across all functional domains (Composite Mean 36.17 ± 26.88), although one child did not show significant deficits. The QI-Disability Form demonstrated a mean total score of 64.8 (±12.7), and the PedsQL-Family Impact Module demonstrated a mean total score of 56.5 (±31.5). Vineland composite scores did not correlate with levels of disability captured by the QI-Disability Form (Pearson Correlation range -0.63 to +0.69, p>0.05 on all subscales). Ultimately, despite genotypic homogeneity, there is notable variability in adaptive functioning and quality of life among affected children that does not correlate with age.

Congenital disorder of glycosylation caused by de novo variant of SLC35A2 gene: a case report / 中华神经科杂志

Congenital disorder of glycosylation (CDG) is a group of genetic metabolic diseases involving multiple organs. A case of CDG caused by SLC35A2 gene mutation was diagnosed. The clinical characteristics included spasms, developmental retardation and multiple malformations. Video-electroencephalogram showed dysrhythmia. A de novo heterozygous missense mutation of SLC35A2 gene was detected by whole exome sequencing: c.844G>A (p.Gly282Arg). It was predicted to be likely pathogenic according to American College of Medical Genetics and Genomics guidelines which had not been reported in China.

Case report of congenital disorder of glycosylation type Ia combined with dilated cardiomyopathy / 中华实用儿科临床杂志

Clinical data and follow-up of a case of congenital disorder of glycosylation type Ia (CDG-Ia) combined with dilated cardiomyopathy admitted to the Department of Cardiology, Children′s Hospital of Nanjing Medical University were analyzed retrospectively.The 5-year-old female patient was admitted in December 2016 due to recu-rrent shortness of breath for 2 months.Clinical symptoms and signs included repeated attacks of shortness of breath, physical retardation, malnutrition, binocular esotropia, multiple episodes of hypoglycemia, hepatosplenomegaly, hypotonia and other multi-system damages.Cardiac echocardiography suggested the feature of dilated cardiomyopathy, including the significant enlargement of the left ventricle, and decreased systolic function.Genetic testing revealed a compound heterozygous mutation in the PMM2 gene, and as a result, the patient was diagnosed as CDG-Ia.The patient′s condition improved after symptomatic treatments such as Cedilanid, Dopamine, Dobutamine, Furosemide, as well as support treatments like myocardium nutrition, blood sugar maintenance, liver protection, etc.After discharge, the patient was given oral Digoxin, Betaloc, Captopril and diuretics, and hypoglycemia-controlling agents.The patient was followed up every 3-6 months.After more than 2 years of follow-up, the heart function and heart enlargement gradually returned to normal.During the Corona Virus Disease 2019 outbreak, self-withdrawal continued for 2 months.Re-examinations showed decreased cardiac function and enlarged left ventricle again.Medications were resumed again, and the patient was followed up closely.This case report suggested that CDG-Ia may be associated with dilated cardiomyopathy, and the cardiac phenotype may be improved by symptomatic supportive treatment.

Cranial cavity filled with cerebrospinal fluid in an otter (Lontra longicaudis) - case report / Cavitação craniana preenchida por fluido cerebroespinhal em lontra (Lontra longicaudis) - relato de caso

Computed tomography of the head of an otter with a history of incoordination, visual deficits, and seizures was performed. Intracranial images revealed a large non-enhancing fluid attenuating cystic lesion in the left frontoparietal region communicating with the left lateral ventricle and subarachnoid space. These findings are consistent with a congenital brain cavity filled by cerebrospinal fluid, with porencephaly being the most probable diagnosis based on the clinical and tomographic findings. The authors highlight the rarity of such a cystic lesion in wild animals, with this being the first report in otters.(AU)

Realizou-se o exame tomográfico do crânio de uma lontra com histórico de incoordenação, déficit visual e convulsões. Imagens intracranianas revelaram grande lesão cística não captante de contraste em região frontoparietal esquerda, apresentando comunicação com o ventrículo lateral esquerdo e espaço subaracnoidea. Esses achados foram consistentes com cavitação cerebral congênita preenchida por fluido cerebroespinhal, sendo porencefalia o diagnóstico de maior probabilidade com base nos achados clínicos e tomográficos. Destaca-se a raridade dessa condição em animais silvestres, sendo este o primeiro relato em lontras.(AU)

Prenatal presentation of a rare genetic disorder: a clinical, autopsy and molecular correlation

Walker Warburg syndrome (WWS) lies at the severe end of the spectrum of the congenital muscular dystrophies. WWS is a congenital disorder of the O-glycosylation that disrupts in the post-translation modification of dystroglycan proteins. WWS is characterized by the involvement of the central nervous system and rarely by multisystem involvement. Next-generation sequencing discovered that multiple genes are associated with this disorder. FKTN is the rarest cause of WWS. We describe a clinical-autopsy report of a molecularly- confirmed WWS case presenting with ventriculomegaly, agenesis of the corpus callosum with a novel phenotype of Dandy-Walker malformation and unilateral multi-cystic kidney. The whole-exome sequencing confirmed a homozygous variant (c.411C>A) in the FKTN gene with a premature termination codon. This case emphasizes the importance of detailed postnatal phenotyping through an autopsy in any pregnancy with antenatally identified malformations. Obstetricians, pediatricians as well as fetal medicine experts need to counsel the parents and focus on preserving the appropriate sample for genetic testing. WWS, though rare deserves testing especially in the presence of positive family history. Dandy-Walker malformation is a novel feature and expands the phenotypic spectrum.

Transcatheter closure of patent ductus arteriosus using duct occluder: an eleven-year experience from a single tertiary cardiac center

Background: Patent Ductus Arteriosus (PDA) is a common congenital disorder. As an isolated lesion, PDA constitutes 6 to 11% of all congenital heart disease. PDA needs closure to eliminate pulmonary over circulation leading to volume overload of left ventricle, pulmonary vascular obstructed disease.Methods: This retrospective study was carried out in pediatric cardiology unit of Institute of Postgraduate Medical Education and Research, Kolkata from September 2005 to August 2016, which included 503 patients.Results: Device closure was attempted in 492 patient’s Procedural success was achieved in 85% cases on table, in who check aortogram revealed complete closure of PDA. In 15% cases, residual shunt was present. In 12% of cases, residual shunt disappeared during follow-up echocardiogram over 6-month follow-up. In 3% cases, small shunt remained at 6-month and 1-year follow up.Conclusion: Transcatheter closure of PDA by duct occluder is safe and effective with good mid-term outcome. The optimum assessment of ductul size and anatomy is crucial for optimum device size, which prevents residual shunt, device embolization and protrusion.

Potter’s syndrome: a case report

Potter’s syndrome is a rare congenital disorder characterized by characteristic atypical appearance of a newborn due to the oligohydroamnios experienced during the intrauterine life. Its incidence varies from 1 in 2000 to 1 in 5000. 40 years old G7P4L1 A2 at 37 weeks of period of gestation was admitted at a tertiary care institute with labour pains. Her previous obstetric history included three full term vaginal deliveries, two of the babies expired in postnatal period of 2 months and 7 days age respectively. One was alive and healthy. In fourth pregnancy she underwent emergency LSCS, but baby expired 5 months after birth. She had history of 2 abortions which were spontaneous and not followed by curettage. She also gave history of intake of some drugs at 6th week of gestation prescribed by a local Baba to have a male child. Her ultrasonography revealed fetus with bilateral renal agenesis. On per abdomen examination, clinically liquor was very much reduced, Fetal heart sounds were not heard. She delivered vaginally a still born fetus with ambiguous genitalia, anal atresia and malformed limbs. The fetus had typical facial appearance of “potter facies”. Potter’s Syndrome or Sequence is a rare fatal disorder. Apart from typical Potter’s facies, pulmonary hypoplasia, skeletal deformities are associated with this condition, severity depends on the degree and duration of oligohydramnios. Therefore, it is very important to pick up this condition during antenatal ultrasound at earlier gestation so that timely decision regarding further workup and pregnancy termination can be undertaken. This case report emphasizes upon the importance of regular antenatal check ups and examination in each and every patient as it picks up the suspicious cases which can lead to further workup, definite diagnosis of the condition and timely decision regarding management.

Clinical and socioeconomic factors associated with delayed orchidopexy in cryptorchid boys in China: A retrospective study of 2423 cases / 亚洲男科学杂志(英文版)

We investigated the associations of clinical and socioeconomic factors with delayed orchidopexy for cryptorchidism in China. A retrospective study was conducted on cryptorchid boys who underwent orchidopexy at Children's Hospital at Chongqing Medical University in China from January 2012 to December 2017. Of 2423 patients, 410 (16.9%) received timely repair by 18 months of age, beyond which surgery was considered delayed. Univariate analysis suggested that the laterality of cryptorchidism (P = 0.001), comorbidities including inguinal hernia/scrotal hydrocele (P < 0.001) or urinary tract disease (P = 0.016), and whether patients lived in a poverty county (P < 0.001) could influence whether orchidopexy was timely or delayed. Logistic regression analysis suggested that the following factors were associated with delayed repair: unilateral rather than bilateral cryptorchidism (odds ratio [OR] = 1.752, P < 0.001), absence of inguinal hernia or hydrocele (OR = 2.027, P = 0.019), absence of urinary tract disease (OR = 3.712, P < 0.001), and living in a poverty county (OR = 2.005, P < 0.001). The duration of postoperative hospital stay and hospital costs increased with the patient's age at the time of surgery.

Congenital disorder of glycosylation type 1a:a case report / 临床儿科杂志

Objective To explore the clinical features, diagnosis, and treatment of congenital disorder of glycosylation type 1a (CDG-Ⅰa), a rare inherited metabolic disease. Methods The clinical data and the gene detection results of one case of CDG-Ia which was discovered because the case had encephalopathy and hepatopathy were retrospectively analyzed. The related literatures were reviewed. Results Male infant suffered with face and trunk rash, motor development retardation, malnutrition, cheek fat plump, low limbs muscle tone, and bilateral crater nipple at 3 months old. Abnormal liver function and mild renal impairment were found after examination. The development quotient was low. Head MRI showed that bilateral frontal and temporal sulcus widening, and cerebellar atrophy. Urinary organic acids, amino acids, carnitine, and biotin activities were normal. Gene sequencing revealed that there were two heterozygous mutations, c.430T>C (p.F144L) and c.713G>C (p.R238P), in the PMM2 gene. The diagnosis of CDG-Ⅰa was confirmed. Both of the infant's parents were healthy, and each of them carries a pathogenic mutation. The infant had an elder brother who had mental disorder and died for liver and kidney function damage and hydronephrosis at 8 months old. Conclusion CDG-Ⅰa is an autosomal recessive disease. For infants with unexplained multiple organ damage, especially combined with intelligent and motor development retardations, strabismus, nipple retraction, and cerebellar atrophy, the possibility of CDG-Ⅰa should be considered. Gene detection of PMM2 can help the diagnosis.

Apert syndrome (Acrocephalosyndactyly): a case report.

Apert syndrome is named for the French physician. Eugene Apert in 1906 described the syndrome acrocephalosyndactylia. It is a rare autosomal dominant disorder characterized by craniosynostosis, craniofacial anomalies, and severe symmetrical syndactyly of the hands and feet (i.e. cutaneous and bony fusion refers to webbing of fingers and toes). Apert syndrome is characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. In addition, a varied number of fingers and toes are fused together (syndactyly). Most cases of Apert syndrome are sporadic, may result from new mutations in the gene. The purpose of this paper is to report a case of Apert syndrome in a female fetus of 30 weeks with asymmetrical skull confirmed by prenatal ultrasonography. Pregnancy was terminated and fetus was submitted for detailed autopsy in anatomy dissection hall. The findings and review of literature were presented in this article.

Pectus carinatum in a dog / Pectus carinatum em um cão

Descreve-se o atendimento de um cão macho de cinco meses de idade, apresentando diversas malformações congênitas, incluindo uma protrusão ventral da parte distal do externo, que foi diagnosticada como Pectus carinatum tendo por base os achados clínicos e radiográficos.

A Case of Hypotrichosis Simplex of the Scalp / 대한피부과학회지

We report a sporadic case of hypotrichosis simplex of the scalp, a rare genotrichosis, characterized by sparse or absent scalp hair with no structural defect of the hair shaft, in the absence of other ectodermal or systemic abnormalities. A 9-year-old girl had normal-looking hair at birth but subsequently lost the hair on her scalp after she turned 3 years of age. However, her eyebrows and eyelashes remained normal. Skin, nails and teeth were also normal except for malocclusion. No other family member had a similar hair defect. Hair shaft examination did not reveal any structural abnormalities. Microscopic examination of a scalp biopsy specimen showed a reduced number of hair follicles.

A bronchogenic cyst presenting as a parathyroidal mass / 대한이비인후과학회지

A bronchogenic cyst is congenital malformation of the foregut which was generally encountered within the mediastinum and detected in pediatric patients with symptoms of infection or compression on vital structures. They are rarely detected in adult population as a neck mass. We have recently experienced one case of bronchogenic cyst as a parathyroid mass in a 50-year-old female. It was incidentally detected by routine neck ultrasonography and interpreted as a parathyroid cyst with hemorrhage preoperatively, but confirmed as a bronchogenic cyst at pathologic examination. We report this case with review of literatures.

Bronchogenic Cyst Presenting as an Anterior Neck Mass / 대한이비인후과학회지

A bronchogenic cyst is an abnormality of pulmonary differentiation, usually detected in pediatric patients. The location of bronchogenic cysts in the midline of anterior neck has been described, but it is known to be quite rare. A case of a 6-year-old male with a palpable mass in the anterior neck is presented. The patient was admitted with a complaint of a 2 X 2 cm sized, soft, non-tender mass in the anterior neck. The clinical impression was that of a thyroglossal duct cyst ; however, the histopathologic diagnosis of a bronchogenic cyst was made on the surgical specimen, Following surgical treatments, the recovery was uneventful. Since masses of the head and neck may encompass a variety of histopathologic diagnoses, it is important to include bronchogenic cysts in differential diagnoses for infants and children.