Inherited Metabolic Disorders Involving the Nervous System

유지숙,Jeesuk Yu The Korea Society of Inherited Metabolic Disease 2023 대한유전성대사질환학회지 Vol.23 No.2

Inherited metabolic disorders (IMD) are a group of disorders caused by defects in specific biochemical pathways. Up to 85% of IMD display predominantly neurological manifestations by affecting neurodevelopment or causing neurodegeneration. These neurometabolic disorders present with a variety of neurological and non-neurological manifestations. Early diagnosis of IMD is important because some disorders can be treated or improved with specific treatment if detected early. For prompt diagnosis and treatment, it is important to suspect IMD by being familiar with the clinical characteristics, biochemical abnormalities, and characteristic neuroimaging patterns that appear in IMD. Genetic testing, including next-generation sequencing, is also important in diagnosing IMD. During the follow-up of patients with IMD, it is necessary to conduct regular physical and neurological examinations in addition to disease-specific management.

ocOrolingual Tremor on Smiling

Sun Ah Choi,Jeesuk Yu,Hee Hwang,Hunmin Kim 대한소아신경학회 2020 대한소아신경학회지 Vol.28 No.1

Thyroid imaging study in children with suspected thyroid dysgenesis

Chun Sangwoo,Lee Young Seok,Yu Jeesuk 대한소아내분비학회 2021 Annals of Pediatirc Endocrinology & Metabolism Vol.26 No.1

Purpose: Thyroid dysgenesis is one of the most common causes of permanent congenital hypothyroidism. Thyroid ultrasonography or scan is used to detect thyroid dysgenesis. We analyzed the sensitivity and specificity of thyroid ultrasonography and scan in diagnosing thyroid dysgenesis to determine the clinical utility of each thyroid imaging method. Methods: Sixty-one patients younger than 7 years of age were investigated via thyroid scan. Nineteen patients who were initially interpreted as having thyroid dysgenesis, such as ectopia, hemiagenesis, or aplasia, by thyroid scan were included in the study. Clinical characteristics and findings of a thyroid imaging study were reviewed. Results: Initially, thyroid scan results were interpreted as ectopia (n=9), hemiagenesis (n=1), and nonvisualization (n=9). In contrast, the results of thyroid ultrasonography were normal thyroid gland (n=5), ectopia (n=6), and hypoplasia (n=8). After reviewing the results of both studies, final imaging diagnoses were as follows: normal thyroid gland (n=5), hemiagenesis (n=1), ectopia (n=9) including 2 dual ectopy, hypoplasia (n=3), and aplasia (n=1). Thyroid ultrasonography showed higher sensitivity and specificity in detecting presence of normal thyroid gland. Thyroid scan was better to detect ectopia. Among 8 patients who were initially interpreted as having hypoplasia by ultrasonography, 4 were confirmed as ectopia and one as aplasia. Conclusion: This study showed that thyroid ultrasonography is useful as the first-line imaging study to detect normal-sized eutopic thyroid gland. Thyroid scan should be performed to investigate the presence of ectopia if hypoplasia or aplasia is suspected by ultrasonography.

Analysis of Dermatologic Diseases in Neurosurgical In-Patients: A Retrospective Study of 463 Cases

( Kyung Min Kim ),( Hei Sung Kim ),( Jeesuk Yu ),( Jong Tae Kim ),( Sang Hyun Cho ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.3

Background: Both the skin and the neurologic system are derived from the ectoderm during embryogenesis, and thus patients with neurologic disorders may have accompanying dermatologic diseases. For example, seborrheic dermatitis is more frequently observed in patients with Parkinsonism and other neurologic disorders. To date, however, there has been limited review on dermatologic diseases in neurosurgical in-patients. Objective: The purpose of this study was to characterize dermatological problems encountered in a neurosurgery unit and to compare these data to previous reports of in-patient dermatologic consultations. Methods: A retrospective review was conducted over all in-patient dermatology consultations from the neurosurgery unit during a 3-year period. Results: Of 2,770 dermatology consultations, 463 (16.7%) came from the department of neurosurgery. The most frequent age group was the 6th decade of life, and the ratio of men to women was 1.07. Consults were most frequently placed from patients with intracranial hemorrhage (23.8%). Eczema/dermatitis (36.5%; n=204) and cutaneous infections (27.0%; n=151) accounted for more than half of all dermatological consultations, followed by cutaneous adverse drug reactions (11.8%; n=66). Additionally, seborrheic dermatitis was significantly more frequent (p=0.048, odds ratio=1.96) in patients with intracranial hemorrhage. Conclusion: This study characterizes the distribution of skin disorders in patients admitted to the neurosurgery service based on the consultations that have been made for dermatologic evaluation. Collaboration between the neurosurgeons and dermatologists may improve the quality of patient care and help to better predict the occurrence of these conditions. (Ann Dermatol 28(3) 314∼320, 2016)

1p36 deletion syndrome confirmed by fluorescence in situ hybridization and array-comparative genomic hybridization analysis

Dong Soo Kang,Eunsim Shin,Jeesuk Yu 대한소아청소년과학회 2016 Clinical and Experimental Pediatrics (CEP) Vol.59 No.no.sup1

Pediatric epilepsy can be caused by various conditions, including specific syndromes. 1p36 deletion syndrome is reported in 1 in 5,000–10,000 newborns, and its characteristic clinical features include developmental delay, mental retardation, hypotonia, congenital heart defects, seizure, and facial dysmorphism. However, detection of the terminal deletion in chromosome 1p by conventional G-banded karyotyping is difficult. Here we present a case of epilepsy with profound developmental delay and characteristic phenotypes. A 7-year- and 6-month-old boy experienced afebrile generalized seizure at the age of 5 years and 3 months. He had recurrent febrile seizures since 12 months of age and showed severe global developmental delay, remarkable hypotonia, short stature, and dysmorphic features such as microcephaly; small, low-set ears; dark, straight eyebrows; deep-set eyes; flat nasal bridge; midface hypoplasia; and a small, pointed chin. Previous diagnostic work-up, including conventional chromosomal analysis, revealed no definite causes. However, array-comparative genomic hybridization analysis revealed 1p36 deletion syndrome with a 9.15-Mb copy loss of the 1p36.33-1p36.22 region, and fluorescence in situ hybridization analysis (FISH) confirmed this diagnosis. This case highlights the need to consider detailed chromosomal study for patients with delayed development and epilepsy. Furthermore, 1p36 deletion syndrome should be considered for patients presenting seizure and moderate-to-severe developmental delay, particularly if the patient exhibits dysmorphic features, short stature, and hypotonia.

1p36 deletion syndrome confirmed by fluorescence in situ hybridization and array-comparative genomic hybridization analysis

Kang, Dong Soo,Shin, Eunsim,Yu, Jeesuk The Korean Pediatric Society 2016 Clinical and Experimental Pediatrics (CEP) Vol.59 No.no.sup1

Pediatric epilepsy can be caused by various conditions, including specific syndromes. 1p36 deletion syndrome is reported in 1 in 5,000-10,000 newborns, and its characteristic clinical features include developmental delay, mental retardation, hypotonia, congenital heart defects, seizure, and facial dysmorphism. However, detection of the terminal deletion in chromosome 1p by conventional G-banded karyotyping is difficult. Here we present a case of epilepsy with profound developmental delay and characteristic phenotypes. A 7-year-and 6-month-old boy experienced afebrile generalized seizure at the age of 5 years and 3 months. He had recurrent febrile seizures since 12 months of age and showed severe global developmental delay, remarkable hypotonia, short stature, and dysmorphic features such as microcephaly; small, low-set ears; dark, straight eyebrows; deep-set eyes; flat nasal bridge; midface hypoplasia; and a small, pointed chin. Previous diagnostic work-up, including conventional chromosomal analysis, revealed no definite causes. However, array-comparative genomic hybridization analysis revealed 1p36 deletion syndrome with a 9.15-Mb copy loss of the 1p36.33-1p36.22 region, and fluorescence in situ hybridization analysis (FISH) confirmed this diagnosis. This case highlights the need to consider detailed chromosomal study for patients with delayed development and epilepsy. Furthermore, 1p36 deletion syndrome should be considered for patients presenting seizure and moderate-to-severe developmental delay, particularly if the patient exhibits dysmorphic features, short stature, and hypotonia.

Congenital hypothyroidism due to thyroglobulin deficiency: a case report with a novel mutation in TG gene

Seung Heo,Ja-Hyun Jang,Jeesuk Yu 대한소아내분비학회 2019 Annals of Pediatirc Endocrinology & Metabolism Vol.24 No.3

Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates and infants with an incidence of one in 2,000 to one in 4,000 newborns. Primary CH can be caused by thyroid dysgenesis and thyroid dyshormonogenesis. CH due to a TG gene mutation is one cause of thyroid dyshormonogenesis and can be characterized by goitrous CH with absent or low levels of serum thyroglobulin (Tg). In the present case, a 15-day-old neonate was referred to us with elevated thyroid stimulating hormone detected during a neonatal screening test. At the age of 34 months, extensive genetic testing was performed, including targeted exome sequencing for hypothyroidism, and revealed compound heterozygous mutations in the TG gene. Sanger sequencing of both parents’ DNA samples revealed a c.3790T> C (p.Cys1264Arg) mutation located at exon 17 inherited from the mother, and a c.4057C> T (p.Gln1353*) mutation located at exon 19 was inherited from the father. The c.4057C> T (p.Gln1353*) mutation located at exon 19 has never been reported and, therefore, is a new discovery. We report a case of primary permanent CH with compound heterozygous mutations of the TG gene, including a novel mutation.

Basal serum luteinizing hormone value as the screening biomarker in female central precocious puberty

You Jung Heo,Young Seok Lee,Jeesuk Yu 대한소아내분비학회 2019 Annals of Pediatirc Endocrinology & Metabolism Vol.24 No.3

Purpose: Precocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP) is caused by premature activation of the hypothalamus-pituitary-gonadal (HPG) axis and causes thelarche in girls before the age of 8. A gonadotropin-releasing hormone (GnRH) stimulation test is the standard diagnostic modality for diagnosing CPP. However, the test cannot always be used for screening because it is expensive and time-consuming. This study aimed to find alternative reliable screening parameters to identify HPG axis activation in girls <8 years old (CPP) and for girls 8–9 years old (early puberty, EP). Methods: From January 2013 to June 2015, medical records from 196 girls younger than 9 years old with onset of breast development were reviewed, including 126 girls who had a bone age (BA) 1 year above their chronological age. All patients underwent a GnRH stimulation test, and 117 underwent pelvic sonography. The girls were divided into 4 groups based on age and whether the GnRH stimulation test showed evidence of central puberty. Subanalyses were also conducted within each group based on peak luteinizing hormone (LH) level quartiles. Results: Basal serum LH level was the most sensitive marker for screening CPP and EP. The cutoff values were 0.245 IU/L for CPP under 8 years old (P=0.049, area under the curve [AUC]=0.764, 88% sensitivity, 48% specificity) and 0.275 IU/L for EP between 8–9 years old (P=0.005, AUC=0.813, 79% sensitivity, 77% specificity). Peak LH level decreased as BMI z-score among subgroups increased when there was no difference in BA; however, higher BA eliminated this effect. Conclusion: : Basal serum LH level is a useful screening parameter for diagnosing CPP and EP in girls. Peak LH levels were lower with increasing BMI z-score, although older BA eliminated this effect.

A Novel Nonsense Variant in the BCL11A Gene in a Male Patient with Intellectual Disability and Epilepsy

Seung Ho Kim,Go Hun Seo,Seung Hwan Oh,정우영,Jeesuk Yu 대한소아신경학회 2023 대한소아신경학회지 Vol.31 No.1

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Growth Responses During 3 Years of Growth Hormone Treatment in Children and Adolescents With Growth Hormone Deficiency: Comparison Between Idiopathic, Organic and Isolated Growth Hormone Deficiency, and Multiple Pituitary Hormone Deficiency

Lim Han Hyuk,Kim Yoo Mi,Lee Gyung Min,Yu Jaehong,Han Heon-Seok,Yu Jeesuk 대한의학회 2022 Journal of Korean medical science Vol.37 No.11

Background: The study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD). Methods: Total 163 patients aged 2–18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment. Results: The baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment. Conclusion: The 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.