• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.17 no.1
• /
• pp.31-37
• /
• 2017

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is an autosomal recessive disorder of the urea cycle that causes hyperammonemia. Two forms of CPS1D are recognized: a lethal neonatal type and a less severe, delayed-onset type. Neonatal CPS1D cases often present their symptoms within the first days of life. Delayed-onset cases are predominantly adolescents or adults, and infantile delayed-onset cases are rare. Severe hyperammonemia in the neonatal period leads to serious brain damage, coma, and death if not treated promptly. Therefore, early diagnosis and acute treatment are crucial. Despite the improvement of treatments, including continuous hemodialysis, ammonia-lowering agents, and a low-protein diet, the overall outcome of severe forms of hyperammonemia often remains disappointing. As the liver is the only organ in which ammonia is converted into urea, liver transplantation has been considered as an elegant and radical alternative therapy to classical dietary and medical therapies. However, liver transplantation has many disadvantages, such as a considerable risk for technical complications and perioperative metabolic derangement, especially in neonates. Additionally, there is a lack of suitable donor organs in most countries. According to recent studies, liver cell transplantation is a therapeutic option and serves as a bridge to liver transplantation. Here, we report a Korean CPS1D patient with novel mutations in CPS1 who was treated by liver cell transplantation after being diagnosed in the neonatal period and showed a good neurodevelopmental outcome at the last follow-up at six months of age.

• Childhood Kidney Diseases
• /
• v.5 no.1
• /
• pp.9-14
• /
• 2001

Purpose : This study was undertaken to investigate clinical aspects of nutcracker syndrome in children including sexual distribution, age of onset, the ratio of peak flow velocity between the narrowed and dilated portions in the left renal vein and prevalence of hematuria or proteinuria. Materials and Method : The subjects included 30 patients diagnosed with nutcracker syndrome using Doppler sonography from September 1999 to January 2001 in Severance Hospital, Department of Pediatric Nephrology. The diagnostic criteria for nutcracker syndrome was a peak flow velocity of ratio is more than 5.0. Results : Patients consisted of 14 males and 16 females. The mean age was 9.19${\pm}$2.31 years old and the ratio of peak flow velocity was 8.52${\pm}$2.24. Age of onset us higher in males 9.68${\pm}$2.82 year old than in females, 8.76${\pm}$1.72 year old respectively(P<0.05). But there was no difference in the ratio of peak flow velocities ; 8.45${\pm}$2.31 in the male group , 8.58${\pm}$2.25 in the female group(P>0.05). There was no difference in the age of onset and the ratio of peak flow velocity between patients with hematuria and without hematuria. Among patients with nutcracker syndrome, 24 cases of hematuria, 3 cases of proteinuria only, and 3 cases of hematuria with proteinuria. Conclusion : In children of school age, early diagnosis of nutcracker syndrome and consistent follow up is worthy of consideration, especially ill the prevention of sequelae. (J. Korean Soc Pediatr Nephrol 5 : 9-14, 2001)

• Pediatric Infection and Vaccine
• /
• v.4 no.1
• /
• pp.79-89
• /
• 1997

Purpose : Neonatal bacterial meningitis is the disease which clinical manifestations are nonspecific and several neurologic complications may occur. We studied neonatal bacterial meningitis, particularly in treatment and prognosis according to causative organisms -gram positive and gram negative bacteria- to assist in treatment of neonatal bacterial meningitis. Methods : We analysed twenty-four cases retrospectively who had been admitted in NICU or pediatric ward in Chung-ang Gil hospital from Jan. 1991 to Jun. 1996, and who had proven causative organisms in culture or latex agglutination[n test in CSF. Results : 1) The ratio of male to female was 2.4: 1. The mean birth weight and gestational age in cases with gram positive bacterial meningitis were $2.91{\pm}0.79kg$ and $38.4{\pm}2.74$ weeks and those in cases with yam negative bacterial meningitis were $3.30{\pm}0.90kg$ and $37.7{\pm}3.33$weeks respectively. There was no significant difference between the two groups. 2) The perinatal predisposing factors were pematurity, mecoinium staining amnionic fluid, matemal diabetes and pregnancy-induced hypertension, etc. The clinical manifestations Were fever, seizure, poor oral intake and fontanel bulging, etc. There were eleven cases with early onset bacterial meningitis(four cases by gram positive bacteria, seven cases by gram negative bacteria), and thirteen cases with late onset bacterial meningitis(seven cases by gram positive bacteria, six cases by gram negative bacteria). There was no significant difference between the two groups in terms of onset. 3) There were eleven cases with yam positive bacterial meningitis and they were coagulase-negative staphylococci(three cases), group B streptococci(three cases), Staphylococcus aureus(two cases), Streptococcus viridans(two cases), and enterococci(one case). And there were thirteen cases with gram negative bacterial menir gitis and they were Escherichia coli(seven cases), Klevsiella pneumoniae(three cases), Pseudomonas aeruginosa(one case), Acinetobactor(one case) and Enterobacter(one case). 4) The initial CSF WBC counts in cases with yam negative bacterial meningitis were significantly higher than those in cases with gram positive bacterial meningitis but the CSF protein and glucose levels were no significant difference in the two groups statistically. 5) The number of cases with abnormal findings in brain ultrasonography was seven in gram positive bacterial meningitis and ten in gram negative bacterial meningitis. 6) There were relatively high sensitivity to penicillin derivatives, the first generation cephalosporin and vancomycin in gram positive bacteria and to the third generation cephalosporin and amikacin in gram negative bacteria. 7) The mortality rate was 20.8%(5 cases were expired or discharged hopelessly). There was no significant difference between the two groups in prognosis. Conclusions : We recommend active treatment in noenatal bacterial meningitis to improve prognosis because the prognosis is poor.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.8 no.2
• /
• pp.157-163
• /
• 2005

Purpose: Dietary protein induced proctocolitis (DPIPC) can be considered as a cause of rectal bleeding or blood streaked stool in otherwise healthy-looking infants in the first several months of life. Failure to appreciate this entity may lead to inappropriate diagnostic or therapeutic intervention. This study aimed to ascertain the clinical features, treatment and prognosis of DPIPC. Methods: We reviewed 13 infants retrospectively, presented with bloody stool in early infancy. They were diagnosed as DPIPC clinically in Pusan National University Hospital from May 2002 to June 2004. Results: Seven males and six females were included. The mean age at onset of bleeding was $96.8{\pm}58.8days$. The mean frequency of hematochezia was $2.6{\pm}2.5$ times a day. Duration from onset of symptom to diagnosis was $35.5{\pm}55.0days$ and duration from onset of symptom to resolution of bleeding was $58.7{\pm}67.0days$. Nine (69.2%) were exclusively breast-fed infants and two (15.4%) were formula-fed infants. All but one infant did not have family history of other allergic diseases. A dietary history of ingestion of cow's milk, nut or shellfish was present in three mothers. Peripheral eosinophil count was normal to slightly elevated (total WBC count $10,555{\pm}3,145/mm^3$, relative eosinophil count $6.3{\pm}3.0%$, absolute eosinophil count $659.0{\pm}532.2/mm^3$). Sigmoidoscopy revealed lymphonodular hyperplasia with surrounding hemorrhagic spots in the rectosigmoid colon in 6 infants. Histopathologic finding of colonic biopsies in 5 infants showed chronic inflammation with lymphoid follicular hyperplasia (5 infants), crypt abscess (3 infants), or mild infiltration of eosinophils (less than 20/high power field) in the lamina propria. Spontaneous resolution of rectal bleeding occurred in all infants without dietary change or medicine. Conclusion: Most infants with DPIPC experience a very benign course and have spontaneous resolution of rectal bleeding without changes in the mother's diet. In the case of strong evidence for DPIPC we suggest deferring further invasive investigation and continuing breast feeding.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.15 no.1
• /
• pp.29-34
• /
• 2015

Citrullinemia type1 is an autosomal recessive disorder of the urea cycle characterized by neonatal or late onset of hyperammonemia caused by a deficiency of the enzyme argininosuccinate synthetase (ASS). An ASS1 deficiency demonstrates fatal clinical manifestations that are characterized by the neonatal metabolic coma and early death when untreated. It causes a broad spectrum of effects, ranging from a mild disorder to a severe mental retardation, epilepsy, neurologic deficits. An acute neonatal form is the most common. Infants are normal at birth followed by an acute illness characterized by vomiting, lethargy, seizures and coma. These medical problems are life-threatening in many cases. A later onset form is less frequent and may be milder than the neonatal form. This later-onset form is associated with severe headaches, visual dysfunction, motor dysfunction, and lack of energy. Citrullinemia type1 is caused by mutations in the ASS1 gene located on chromosome 9q34.1 that encodes argininosuccinate synthetase, the third enzyme of the urea cycle catalyzing the formation of argininosuccinic acid from citrulline and aspartic acid. The enzyme is distributed in tissues including liver and fibroblasts. This mutation leads to hyperammonemia, arginine deficiency and elevated citrulline level. In the urea cycle, argininosuccinate synthetase catalyses the conversion of citrulline and aspartate to argininosuccinate.. Here, we describe a female newborn patient with lethargy, rigidity and hyperammonemia who was diagnosed as citrullinemia type1 with a c.[421-2A>G], c.[1128-6_1188dup] mutation.

• Childhood Kidney Diseases
• /
• v.8 no.2
• /
• pp.195-204
• /
• 2004

Purpose: Hypophosphatemic rickets is a hereditary disease, characterized by hypophosphatemia due to renal phosphate wasting, impaired renal production of 1,25-dihydroxyvitamin $D_3$, rachitic bone deformities and impaired growth. The purpose of this study is to provide clinical profiles of patients with hypophosphatemic rickets in our hospital. Methods: Between July 1983 and February 2004, 56 patients were diagnosed as having hypophosphatemic rickets. The medical records of these patients were reviewed retrospectively. Clinical manifestations, family histories, laboratory data, treatment outcomes were described. Results: Fifty six patients were enrolled in this study. The average age at symptom onset and diagnosis were 20 months and 5 years respectively. Fourteen patients had family histories. The main clinical manifestations were bow legs and short stature. There was a significant negative correlation between the ages and the height z-scores at the time of diagnosis(r=-0.47, P=0.005). Initial laboratory data showed normocalcemia, hypophosphatemia, elevated serum alkaline phosphatase, decreased tubular reabsorption of phosphate and a normal range of 1,25-dihydroxyvitamin $D_3$ Radiographic examinations of bone revealed fraying, widening and cupping of the metaphyseal ends. Treatment consisted of Joulie solution and vitamin D metabolites, and resulted in improved biochemical and radiographic findings. However, height z-scores remained essentially unchanged(P=0.224). Complications of treatment were frequently observed, including hyperparathyroidism, nephrocalcinosis, and hypercalciuria. Sixteen patients had corrective osteotomy and 4 of them underwent leg lengthening together. Conclusion: There was a gap of several years between the onset of symptoms and the diagnosis. Early treatment seems to be essential to growth. For the earlier treatment, the offsprings of affected parents should be followed up closely.

• Clinical and Experimental Pediatrics
• /
• v.46 no.12
• /
• pp.1224-1229
• /
• 2003

Purpose : Bacterial meningitis is a serious disease, especially in the neonatal period, and it carries a significant degree of mortality and morbidity. Group B streptococcus(GBS) is a common cause of neonatal bacterial meningitis. The purpose of this study was to evaluate the clinical manifestations, treatment results and complications of GBS meningitis. Methods : We analyzed 29 cases retrospectively who had been admitted to the pediatric ward or NICU in Asan Medical Center from May 1990 to January 2002. They had proven GBS in culture or latex agglutination test in CSF. Results : The male to female ratio was 1 : 1.9. There were two cases of early onset type and 27 cases of late onset type. All cases had normal birth weight with full term at delivery. The perinatal predisposing factors were premature rupture of membrane(two cases), and maternal colonization(two cases). The most common presenting symptoms were fever and irritability. Associated diseases were GBS sepsis(21 cases). There was relatively high sensitivity to penicillin derivatives. There were abnormal brain CT or MRI findings in 16 cases(64%), such as infarction, encephalomalatic change, effusion, hydrocephalus, hemorrhage and abscess. The intensive care unit admission rate and the incidence of DIC were higher in the group with complications. Two cases were discharged against advice. Conclusion : We recommend early detection and active treatment in Group B streptococcal meningitis to improve the prognosis.

• Clinical and Experimental Pediatrics
• /
• v.51 no.9
• /
• pp.964-970
• /
• 2008

Purpose : Methylmalonic aciduria (MMA) and propionic aciduria (PA) are inborn errors in the catabolism of branched-chain amino acids. The study was undertaken to investigate the genotypes and clinical features of Korean patients with MMA and PA. Methods : This study examined 12 patients with MMA and eight with PA. We analyzed various clinical features, laboratory findings, treatments, and neuro-developmental outcomes. Diagnoses were based on the presence of characteristic compounds detected by amino acid analysis in serum and organic acid analysis in urine. Mutation analysis was performed in the genes of MUT, MMAA, MMAB, and MMACHC for MMA and PCCA and PCCB for PA. Results : Among the 20 patients, six patients were diagnosed before one month of age and nine patients were diagnosed after the newborn period. Five patients were diagnosed via a neonatal screening test. Patients with early-onset forms had more severe illness at presentation and generally poor outcomes. A favorable outcome was obtained in 55% patients; most of them were of a late-onset type or diagnosed by neonatal mass screening test without symptoms. Genotypes were confirmed in all patients with MMA. We detected 11 different mutations by MUT gene analysis in 10 patients, and three different mutations in MMACHC genes in two patients. PCCA and PCCB gene mutations were identified in 14 of the 16 alleles, in eight patients with PA. Conclusion : Organic aciduria is a fatal disease; however, better outcomes are expected whenever early diagnosis and prompt management are made possible. Mutation analysis is useful for confirming diagnoses and planning management strategies.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.16 no.2
• /
• pp.57-61
• /
• 2016

Isovaleric acidemia (IVA) is an autosomal recessively inherited organic acid disorder due to a defect of the enzyme isovaleryl-CoA dehydrogenase in the leucine metabolic pathway. Deficiency of this enzyme results in the accumulation of derivatives of isovaleryl-CoA. In acute illness in IVA, isovaleric acid and its derivatives accumulate and profound metabolic acidosis with ketosis, characteristic pungent body odor, hypoglycemia, and hyperammonemia can be developed. Additionally, recurrent vomiting, failure to thrive, developmental delay, epilepsy and mental retardation are chronic presenting symptoms and signs for IVA. On the result of newborn screening for inherited metabolic disorders, increased levels of isovalerylcarnitine (C5) are shown. However, C5 elevation can be accompanied with short/branched-chain acyl-CoA dehydrogenase (SBCAD) and therapy with certain antibiotics containing pivalic acid. Quantitative measurement of organic acids in urine and acylcarnitine profiles in plasma are necessary to differential diagnosis. Molecular genetic analysis of the IVD gene for IVA and ACADSB is also helpful to confirm IVA and SBCAD deficiency, respectively. Considering that IVA can be associated with significant morbidity and mortality at acute presentation of metabolic crisis, early diagnosis prior to the onset of symptoms by newborn screening enable to introduction of early treatment and prevention of acute and chronic complications.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.6
• /
• pp.681-690
• /
• 1997

Loss of synaptic transmission and accumulation of extracellular $K^+([K^+]_O)$ are the key features in ischemic brain damage. Here, we examined the effects of several $K^+$channel modulators on the early ischemic changes in population spike (PS) and $[K^+]_o$ in the CA1 pyramidal layer of the rat hippocampal slice using electrophysiological techniques. After onset of anoxic aglycemia (AA), orthodromic field potentials decreased and disappeared in $3.3{\pm}0.22\;min$ $(mean{\pm}SEM,\;n=40)$. The hypoxic injury potential (HIP), a transient recovery of PS appeared at $6.0{\pm}0.25\;min$ (n=40) in most slices during AA and lasted for $3.3{\pm}0.43\;min$. $[K^+]_o$ increased initially at a rate of 0.43 mM/min (Phase 1) and later at a much faster rate (12.45 mM/min, Phase 2). The beginning of Phase 2 was invariably coincided with the disappearance of HIP. Among $K^+$ channel modulators tested such as 4-aminopyridine (0.03, 0.3 mM), tetraethylammonium (0.1 mM), NS1619 $(0.3{\sim}10\;{\mu}M)$, niflumic acid (0.1 mM), glibenclamide $(40\;{\mu}M)$, tolbutamide $(300\;{\mu}M)$ and pinacidil $(100\;{\mu}M)$, only 4-aminopyridine (0.3 mM) induced slight increase of $[K^+]_o$ during Phase 1. However, none of the above agents modulated the pattern of Phase 2 in $[K^+]_o$ in response to AA. Taken together, the experimental data suggest that 4-aminopyridine-sensitive $K^+$channels, large conductance $Ca^{2+}-activated$ $K^+$ channels and ATP-sensitive $K^+$ channels may not be the major contributors to the sudden increase of $[K^+]_o$ during the early stage of brain ischemia, suggesting the presence of other routes of $K^+$ efflux during brain ischemia.