• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.17 no.2
• /
• pp.48-54
• /
• 2017

Purpose: Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal-recessive disorder characterized by early-onset hypotonia associated with brain malformations in dystroglycanopathy. Although the wide spectrum of congenital muscular dystrophies causes difficulty in diagnosis, correlating the genotype with the clinical phenotype can help diagnose FCMD. Here, we evaluated the correlation of targeted molecular genetic analysis of FKTN gene mutation with the FCMD phenotype. Methods: This study was conducted retrospectively with 9 subjects. Inclusion criteria included clinical symptoms characterized by early-onset hypotonia with magnetic resonance imaging (MRI) featuring brain malformations. FKTN gene-alteration analysis was performed using various FKTN gene-analysis methods, including sequencing. Results: Among the 9 subjects studied, 4 (44.4%) were male and 5 (55.6%) were female. The median age of onset of the first symptom was 3.1 months. The first symptom was a delayed milestone in 6 cases (66.7%). All 9 subjects (100%) presented with early-onset hypotonia and global delayed development. All subjects presented with cortical malformation in their brain MRIs. Of the 9 subjects, 6 subjects had previously undergone muscle biopsy and 4 cases (4/6; 66.7%) showed dystrophic or myopathic features. Pathogenic mutations causing FCMD were identified in 3 cases. Conclusions: In this study, all 3 subjects with FKTN mutations showed important MRI findings (pachygyria and cerebellar dysplasia). These data suggest that patients with characteristic phenotypes who show pachygyria and cerebellar abnormalities in brain MRIs may have a high probability of being diagnosed with FCMD.

• Clinical and Experimental Pediatrics
• /
• v.54 no.2
• /
• pp.51-54
• /
• 2011

Vitamin D is present in two forms, ergocalciferol (vitamin $D_2$) produced by plants and cholecalciferol (vitamin $D_3$) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 $[1,25(OH)_2D]$, plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of $1,25(OH)_2D$ from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the $1{\alpha}$-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D $1{\alpha}$-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of $1,25(OH)_2D$ despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human $1{\alpha}$-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and $1{\alpha}$-hydroxylase mutations with clinical findings.

• Korean Journal of Applied Biomechanics
• /
• v.16 no.4
• /
• pp.73-81
• /
• 2006

The purpose of this study was to investigate the effects of strength training on knee joint torque during walking in an adolescent with trisomy-21 Down syndrome. One adolescent with Down syndrome and one normal child participated in this study. Strength training consisted of eight exercises: squat, hamstring curl, hip adduction, hip abduction, knee extension, toe raise, sit-ups, and hyperextension of the waist. The participant with Down syndrome was participated in strength training for 12 weeks, three times a week, three sets, 10-15 RM; resistance was adjusted according to the principle of progressive overload. To measure the effect of strength training, isokinetic strength variables and knee joint torques were measured before training and after 12 weeks of training. The participant with Down syndrome had some abnormalities in controlling knee motion during walking due to muscle hypotonia, ligament laxity, and weakness of muscles. Post-training isokinetic strength increased compared to pre-training measurements. Knee range of motion were increased after strength training. Strength training did not affect ad/adduction and in/exteranl moments but did have an effect on flexor/extensor moment and timing.

• Clinical and Experimental Pediatrics
• /
• v.55 no.7
• /
• pp.224-231
• /
• 2012

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting) are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and postfertilization mitotic nondisjunction (Mit). Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH) receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS.

• Clinical and Experimental Pediatrics
• /
• v.49 no.11
• /
• pp.1158-1166
• /
• 2006

Purpose : The purpose of this study is to make a diagnostic classification and discuss a diagnostic strategy of floppy infants by investigating clinical, neurological, electrophysiological, and genetic analysis of infants admitted to intensive care units with the complaint of hypotonia. Methods : A retrospective study was performed from Jan. 1993 to Dec. 2005 in neonatal and pediatric intensive care units of Seoul National University Children's Hospital. Clinical features and all tests related to hypotonia were investigated. Results : There were 21 cases of floppy infants admitted to intensive care units. Final diagnosis was classified as centra (7 cases[33.3 percent]), peripheral (11 cases [52.4 percent]), and unspecified (3 cases [14.3 percent]). Among the central group, three patients were diagnosed as hypoxic ischemic encephalopathy, two patients as Prader-Willi syndrome, one patient as chromosomal disorder, and one patient as transient hypotonia. Among the peripheral group, four patients were diagnosed as myotubular myopathy, three patients as SMA type 1, two patients as congenital myotonic dystrophy, one patient as congenital muscular dystrophy, and one as unspecified motor-neuron disease. Motor power was above grade 3 on average, and deep tendon reflex was brisk in the central group. Among investigations, electromyography showed 66 percent sensitivity in the peripheral group, and muscle biopsy was all diagnostic in the peripheral group. Brain image was diagnostic in the central group, and Prader-Willi FISH or karyotyping was helpful in diagnosis in central group. Morbidity and mortality was more severe in the peripheral group Conclusion : Classification of diagnosis by clinical characteristics in this study, and application of investigations step by step, may provide an effective diagnostic strategy.

• Journal of Genetic Medicine
• /
• v.6 no.2
• /
• pp.161-165
• /
• 2009

Pompe disease (glycogen storage disease type II) is an autosomal recessive disorder caused by deficiency of acid-${\alpha}$-glucosidase (GAA) resulting in lysosomal glycogen accumulation in multiple tissue, particularly cardiac and skeletal muscle. The classic infantile form of Pompe disease is characterized by marked cardiomegaly, respiratory failure and severe generalized hypotonia. Most patients die from cardiorespiratory failure or respiratory infection within the first year or two of life without treatment. A "non-classic" phenotype presents with less severe clinical feature and slow progression of disease. We report two patients with non-classic infantile Pompe disease from one family manifested hypertrophic cardiomyopathy and progressive proximal weakness.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.12 no.1
• /
• pp.42-48
• /
• 2012

Pompe disease is a rare lysosomal glycogen storage disorder caused by a total or partial deficiency of the acid ${\alpha}$-glucosidase (GAA) enzyme due to the GAA gene mutations. The classic infantile form of Pompe disease is a rapidly progressive multi-organ disease with hypotonia, generalized muscle weakness, and hypertrophic cardiomyopathy, usually leading to death in the first 2 years of life. Enzyme replacement therapy with recombinant human GAA has been shown to be effective and subsequently yielded promising results. Here, we present clinical and genetic characteristics of three Korean non-classic infantile Pompe patients, and the short term efficacy of enzyme replacement therapy. Considering that enzyme replacement therapy can change the natural course of infantile Pompe disease, early diagnosis and early initiation of treatment is critical to improving patient outcomes.

• Journal of the korean academy of Pediatric Dentistry
• /
• v.29 no.2
• /
• pp.237-242
• /
• 2002

Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare genetic disorder involving eyes, kidney and nervous system, and occurs predominantly in mostly males. The patients with Lowe syndrome are characterized with prominent forehead, thin and sparse hair, protruding ears, congenital cataracts, glaucoma, mental retardation, stunted growth, hypotonia, decrease in muscle mass and tendon reflexes, renal tubular dysfunction, and metabolic bone disease. A 6-year-old boy with Lowe syndrome was admitted to our clinic, with multiple caries and a chief complaint of intermittent pain on the left mandibular molar area. Because of difficulty in management of behavior and his medical problem, general anesthesia was performed for dental care. No specific complication was noticed during dental treatment procedure under general anesthesia and also during periodic recall-checks. General anesthesia itself, however, could be a potentially life-threatening procedure due to patient's biomedical problems. When a dental procedure under general anesthesia is to be required in patient with Lowe syndrome, it may be advisable being teamed with physicians, and general anesthesia duration should be as short as possible.

• Childhood Kidney Diseases
• /
• v.23 no.2
• /
• pp.111-115
• /
• 2019

Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in CYP27B1. Clinical findings are growth retardation, hypotonia, muscle weakness, hypocalcemic seizures, and radiological features of rickets. We aimed to present the VDDR1A case with a genetic study of CYP27B1. The 14-month-old boy was admitted to the hospital due to a seizure. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), 25(OH) vitamin D, and 1,25(OH)2 vitamin D values were 5.1 mg/dL, 3.7 mg/dL, 705 IU/L, 429 pg/mL, 24.9 ng/mL, and 8.8 pg/mL, respectively. Radiological study showed cupping and fraying of the distal ulna and radius. The molecular genetic study revealed that the patient had a compound heterozygous mutation, $Phe443Profs^*24$ and c.589+1G>A, in CYP27B1. Genetic analysis of the family members presented that the mother was heterozygous for the mutation c.589+1G>A, and that the father was heterozygous for $Phe443Profs^*24$. The patient was treated with calcium lactate and calcitriol. Until now, six Korean patients with VDDR1A have been studied. Including this case, Korean patients with VDDR1A were found to have only three different mutations in 14 alleles, indicating that the mutation in the CYP27B1 gene is homogeneous in the Korean population.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.18 no.3
• /
• pp.95-98
• /
• 2018

A striking feature of mitochondrial disorders is the vast heterogeneity in their clinical symptoms that ranges from a single organ to severe multisystem involvement. Though a variety of ocular symptoms such as ptosis, pigmentary retinal degeneration, external ophthalmoplegia, and optic nerve atrophy can occur in association with mitochondrial cytopathies, progressive bilateral cataracts are rare among their ocular findings. A 5-year-old girl with no previous medical history came to our hospital presenting symptoms of seizure. She started showing progressive developmental regression, increased seizure frequency, hypotonia, general weakness, dysphagia and decreased vision. Lactic acidosis was noted in metabolic screening test and we confirmed mitochondrial respiratory chain complex I defect in spectrophotometric enzyme assay using the muscle tissue. Progressive bilateral cataracts then developed and were fully evident at the age of 7. She underwent cataract extraction with posterior chamber lens implantation. We are reporting a case of mitochondrial respiratory chain defect with multiorgan involvements including bilateral progressive cataract, an uncommon ocular manifestation. Ophthalmologic evaluation is highly recommended not to overlook the possible ocular manifestations in mitochondrial disorders.