Clinical Manifestations, Gene Analysis of Patients with 3-Methylcrotonyl-CoA Carboxylase Deficiency

OBJECTIVE: 3-Methylcrotonyl CoA carboxylase deficiency (3MCCD) is classified as organic acid disease due to leucine catabolism. It is among the most common inborn errors of metabolism identified on newborn screening test using tandem mass spectrometry. There is a broad spectrum of clinical presentations. 3-Methylcrotonyl CoA carboxylase converts 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA using biotin as a coenzyme in mitochondria. Restricting protein diets and supplementing carnitine, glycine, and biotin are known treatments. We reported this study to find out clinical symptoms, type of gene mutation, and effect of treatment. METHODS: This study was based on retrospective data of patients with 3MCCD in Soonchunhyang University Seoul Hospital and Soonchunhyang University Bucheon Hospital between April 2009 to August 2016. RESULTS: All 10 infants were born term infants and had no symptoms. During the neonatal period, abnormalities were detected in the new born screening test using tandem mass spectrometry, 3-hydroxyisovalerylcarnitine was increased. 3-Methylcrotonylglycine (3MCG) and 3-hydroxyisovalreric acid (3HIVA) were examined in urine organic acid assay. The results showed that 3MCG was increased in all 10 children. Except for three of the 10 children, 3HIVA was increased. Genetic tests were performed on all 10 children. MCCC1 gene mutations were detected in four patients and MCCC2 mutations were detected in six patients. After diagnosis, all children were recommended leucine-restricted diets, and seven of the 10 patients started to feed on leucine free formula for the treatment of 3MCCD. CONCLUSION: According to our data, all patients has no symptoms and are shown normal development. There were no clinical symptoms or changes in prognosis according to gene mutation type.

Effect of herbal extracts on bone regeneration in a rat calvaria defect model and screening system

OBJECTIVES: The aim of this study was to evaluate the effects of herbal extracts on bone regeneration. Two known samples were screened. MATERIALS AND METHODS: We previously established a rat calvaria defect model using a combination of collagen scaffold and herbal extracts. An 8 mm diameter trephine bur with a low-speed dental hand piece was used to create a circular calvaria defect. The experimental group was divided into 4 classifications: control, collagen matrix, Danshen with collagen, and Ge Gan with collagen. Animals in each group were sacrificed at 4, 6, 8, and 10 weeks after surgery, and bone regeneration ability was evaluated by histological examination. RESULTS: Results revealed that both Danshen and Ge Gan extracts increased bone formation activity when used with collagen matrix. All groups showed almost the same histological findings until 6 weeks. However, after 6 weeks, bone formation activity proceeded differently in each group. In the experimental groups, new bone formation activity was found continuously up to 10 weeks. In the Danshen and Ge Gan groups, grafted materials were still present until 10 weeks after treatment, as evidenced by foreign body reactions showing multinucleated giant cells in chronic inflammatory vascular connective tissue. CONCLUSION: Histological analyses showed that Danshen and Ge Gan extractions increased bone formation activity when used in conjunction with collagen matrix.

The developmental biology of birth defect

Knowledge of developmental biology is essential for clinicians who seek to develop a rational approach to the diagnostic evaluation of patients with birth defects. After an accurate diagnosis, a clinician can make predictions about prognosis, recommend management options, and provide an indication of recurrence risk for the parents and relatives. In this paper, we first review the basic mechanisms of embryological development and clinical dysmorphology. We then review cellular and molecular mechanisms in development and related congenital anomalies. Developmental anomalies have a major impact on public health. Genetic counseling and prenatal diagnosis, with the option to continue or to terminate a pregnancy, are important for helping families faced with the risk of a serious congenital anomaly in their offspring. Moreover, primary prevention of birth defects, for example, supplementation of prenatal folic acid and prevention of consumption of alcohol which has teratogenic effects, can be accomplished using developmental biology knowledge.

Causes of Reoperation after Midurethral Sling Procedures in Female Stress Urinary Incontinence

PURPOSE: Midurethral sling procedure has become one of the most commonly performed procedures for the treatment of female stress urinary incontinence(SUI). Although complication rate is very low, some patients are required further treatment to correct unwanted problems after surgery as it continues to be more widely used. We evaluated the mesh-related complications in those who required further procedures after midurethral sling procedures. MATERIALS AND METHODS: From January 2000 to December 2005, female patients who underwent additional surgery because of complications after midurethral sling procedures for stress urinary incontinence were evaluated in this study. RESULTS: In 675 patients, 298 received a tension-free vaginal tape(TVT) and 377 received a Monarc(transobturator route, TOT) as a sling material at 3 different hospitals. 34(5.0%) out of 675 patients required additional surgery to correct complications including obstructive voiding symptoms, mesh extrusion, failed or recurred SUI, wound pain and mesh in the bladder. Mean age of 34 patients was 54.7, and TVT was used in 21(7.0%) out of 298 patients, Monarc was used in 12(3.4%) out of 377 as midurethral sling materials. In 19 patients who showed obstructive voiding symptoms, all were cured by mesh cutting and in 8 patients who complained of immediate recurrence of SUI, 7 showed complete dryness by shortening the loosen mesh. Mesh extrusion with vaginal erosion were observed in 3 and all were cured by segmental resection of mesh without recurrence of SUI. 2 patients who showed recurrence of SUI after 2 years of TVT received Monarc procedure. Mesh in the bladder which was found after 6 months of TVT was managed by endoscopic resection of mesh with Monarc procedure in 1, and suprapubic pain after TVT was improved by resection of TVT segment through suprapubic incision in 1. All reoperation procedures were performed by local anesthesia except 1(mesh in the bladder). CONCLUSION: These data demonstrate that midurethral sling is an excellent surgical procedure with low complication rate, high success rate in reoperation. However, care must be taken to reduce reoperation rate in applying tension of mesh on urethra because most patients(27 out of 34) who required reoperation have complained of obstructive voiding symptoms(19) and persistent incontinence(8).

Amino acid metabolism disorders / 한양의대학술지

Deficiencies of enzymes involved in amino acid metabolism frequently result in accumulation of toxic substances and subsequent organ damage. The brain, liver and kidneys are the most frequently affected organs. Acute symptoms are often associated with catabolic states that lead to the breakdown of endogenous proteins and the release of large amounts of amino acids. The clinical features result from the toxicity of the deficiency, and the extent of protein intake or endogenous amino acid release in protein compensation. Many disorders of this group are recognised by neonatal screening with tandem MS. Most aminoacidopathies are caused by deficiencies of cytosolic enzymes and are recognised by amino acid analysis in plasma (or urine). Treatment usually involves(a) protein restriction, (b) supplementation of amino acids with unimpaired metabolism as well as trace elements, and (c) specific measures for detoxification if indicated. Treatment is not restricted to childhood but usually must be continued throughout life.

Bone Changes in Phenylketonuria

PURPOSE: While treating 14 phenylketonuria(PKU) patients, we evaluated bone density, changes in bone age, andbony changes such as spiculation or metaphyseal widening. MATERIALS AND METHODS: A total of 14 PKU patients agedbetween 1 month and 14 years(mean, 6.4 years) were under dietary treatment. Eight and eleven patients underwentradiography of the left hand and wrist and bone densitometry(BMD) of the lumbar spine, respectively. The resultswere reviewed with regard to abnormal bony changes, delayed bone age, and osteopenia. Patients were assigned toeither the early or late treatment group, depending on whether or not dietary therapy was started before 3 monthsof age. Those in whom a blood phenylalanine level of under 10 mg/dl was maintained were assigned to the 'goodcontrol' group; others were classified as 'variable control'. The findings of radiographs of the left hand andlumbar BMD were evaluated in relation to the time of dietary therapy, and adequacy of treatment. RESULTS: Onlumbar BMD, four of 11 patients (36%) showed reduced bone density of more than 1 S.D. None of the 11 who underwentradiography of the left hand showed bony abnormalities such as spiculation or metaphyseal widening. In four of the11, bone age was less than chronological age by at least one year. According to Fisher's exact test there was norelation between delayed bone age , osteoporosis and the time and adequacy of dietary therapy (p >0.05). CONCLUSION: None of the 14 PKU patients who underwent dietary therapy had bony abnormalities such as spiculationor metaphyseal widening. In four of the 11, bone age was at least one year less than chronological age, and onlumbar BMD, osteoporosis was seen. For the evaluation of bone change in PKU patients, plain radiography and BMDare thus complementary.

Contractile Responses of Rat Seminal Vesicle to Field Stimulation, Phenylephrine, Acetylcholine and KCI in Anoxia / 대한비뇨기과학회지

Oxygen supply is considered to one of the most important local factors influencing the contractility of smooth muscle. However, the effect of anoxia on the contractility is not uniform throughout the organs containing smooth muscle. This study was undertaken to evaluate the changes of the contractility of rat seminal vesicle to field stimulation, phenylephrine (Phe), acetylcholine (Ach), and KCI in anoxia. Seminal vesicle was rapidly removed from Sprague-Dawley rats which had been killed by cervical dislocation. Spiral segments were mounted in organ bath containing Tyrode's solution at 37'C and equilibrated with 95% O2 and 5% CO2 for 1 hr. Anoxia was produced by changing the gas mixture to 95% N2, 5% CO2. The effect of anoxia on the contractile responses to field stimulation, Phe, Ach, and KCI was determined at different times after the initiation of anoxia. The results of this study can be summarized as follows: 1. Anoxia induced a time-dependent decrease of the contractile responses to field stimulation (30 and 60 Hz). 2. Anoxia potentially inhibited the rhythmic contractions to Phe and Ach. However, the basal tension showed a transient relaxation followed by a contraction after 10 min. 3. In tonic contraction produced by KCI, anoxia caused a transient relaxation followed by a further contraction. However, this anoxic contraction was not inhibited by verapamil (0.1M). This study demonstrated that anoxia may cause poor contractile responses to field stimulation and increased basal tension to Phe, Ach, and KCI. But anoxic contraction by KCI was not inhibited by verapamil, which means that this anoxic contraction of rat seminal vesicle is not mediated by Ca++ influx.

A Case Report of Congenital Ileal Atresia with Microcolon

This is a case report of the congenital ileal atresia with disuse microcolon. The patient was a 3 day-old male newborn infant who was admitted in department of pediatrics Soon Chun Hyang Hospital with complaints of persistant vomitings, no meconium passage, and jaundice from a few hours after birth. The diagnosis was established by characteristic clinical features and barium enuma and finally confirmed by operationl. The operative findings showed that entire colon showed very narrow lumen and was associated with malrotation of the cecum, volvulus of midgut, multiple bands formation, and atresia of ileum with marked dilated proximal small bowel. It is considered that this microcolon was originated from non-use of the colon due to atreisa of the ileum. Resection of the obstructed ileum with multiple bandlysis and finally ileo-ileal end to end anastomosis were done. Microscopic findings showed that sections of cord like mass revealed marked narrowing of mucosal lumen with collections of mucus and necrotic cell debris and lack of mucosa. He was discharged 50 days after operation with favorable condition and normal finding of follow-up barium enema. A brief review of related literature was also presented.