Purpose

Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder caused by a deficiency of iduronate-2 sulfatase (IdS), which is involved in the degradation of glycosaminoglycan (GAG). In this study, the frequency of fasting hypoglycemia in patients with MPS II was investigated and changes in accumulation of glycogen and GAG in the hepatocytes of IdS-knockout (KO) mice were evaluated before and after recombinant IdS enzyme replacement therapy (ERT).

Materials and Methods

Plasma glucose levels were evaluated after an 8-hour fast in 50 patients with MPS II. The IdS-KO mice were divided into three groups (group 2; saline, group 3; 0.15 mg/kg of IdS, and group 4; 0.5 mg/kg of IdS); wild-type mice were included as controls (group 1). ERT was initiated intravenously at four weeks of age, and continued every week until 20 weeks of age.

Results

The mean glucose level after an 8-hour fast was 94.1 ± 23.7 mg/dL in the patients with MPS II. Two (4%) out of 50 patients had fasting hypoglycemia. For the mice, GAG in the lysosomes nearly disappeared and glycogen particles in the cytoplasm were restored to the normal range in group 4.

Conclusion

Glucose metabolism in patients with MPS II appeared to function well despite hepatocytic GAG accumulation and hypothetical glycogen depletion. A higher dose of IdS infusion in MPS II mice led to disappearance of lysosomal GAG and restoration of glycogen to the cytoplasm of hepatocytes.

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder that is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. This syndrome has a characteristic phenotype including severe neonatal hypotonia, early-onset hyperphagia, development of morbid obesity, short stature, hypogonadism, learning disabilities, behavioral problems, and psychiatric problems. PWS is an example of a genetic condition caused by genomic imprinting. It can occur via 3 main mechanisms that lead to the absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and an imprinting defect. Over 99% of PWS cases can be diagnosed using DNA methylation analysis. Early diagnosis of PWS is important for effective long-term management. Growth hormone (GH) treatment improves the growth, physical phenotype, and body composition of patients with PWS. In recent years, GH treatment in infants has been shown to have beneficial effects on the growth and neurological development of patients diagnosed during infancy. There is a clear need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy in patients with PWS.

Mucopolysaccharidosis (MPS) III has 4 enzymatically distinct forms (A, B, C, and D), and MPS IIIC, also known as Sanfilippo C syndrome, is an autosomal recessive lysosomal storage disease caused by a deficiency of heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT). Here, we report a case of MPS IIIC that was confirmed by molecular genetic analysis. The patient was a 2-yr-old girl presenting with skeletal deformity, hepatomegaly, and delayed motor development. Urinary excretion of glycosaminoglycan (GAG) was markedly elevated (984.4 mg GAG/g creatinine) compared with the age-specific reference range (<175 mg GAG/g creatinine), and a strong band of heparan sulfate was recognized on performing thin layer chromatography. HGSNAT enzyme activity in leukocytes was 0.7 nmol/17 hr/mg protein, which was significantly lower than the reference range (8.6-32 nmol/17 hr/mg protein). PCR and direct sequencing of the HGSNAT gene showed 2 mutations: c.234+1G>A (IVS2+1G>A) and c.1150C>T (p.Arg384*). To the best of our knowledge, this is the first case of MPS IIIC to be confirmed by clinical, biochemical, and molecular genetic findings in Korea.

Purpose

Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups.

Methods

The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP), pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS), weight standard deviation score (WSDS), and body mass index standard deviation score (BMISDS) of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic.

Results

The PP groups comprised fast puberty (67%), premature thelarche (17%), true PP (15%), and pseudo PP (1%). Advanced bone age and levels of estradiol, basal luteinizing hormone (LH), and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P<0.05).

Conclusion

The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group.

Purpose

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients' quality of life.

Method

MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The GALNS gene was analyzed. Patients' charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results.

Result

Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different GALNS mutations. Two mutations, c.451C>A and c.1000C>T, account for 37.5% (6/16) and 25% (4/16) of all mutations in this samples, respectively.

Conclusion

An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of atlantoaxial subluxation.

Rabson-Mendenhall syndrome (RMS) is a rare syndrome manifested by extreme insulin resistance with hyperinsulinemia, acanthosis nigricans, tooth dysplasia and growth retardation. Our patient was first noted at the age of 8 months due to pigmentations on skin-folded areas. Initial laboratory tests showed normal fasting glucose (69 mg/dL). Fasting insulin level was severely elevated, up to 554.6 µIU/mL, and c-peptide level was increased, up to 13.81 ng/mL. However, hemoglobin A1c was within normal range (4.8%). He is now 11 yr old. His growth development followed the 5-10th percentile and oral hypoglycemic agents are being administered. The last laboratory results showed insulin 364.1 µIU/mL, C-peptide 4.30 ng/mL, and hemoglobin A1c 7.6%. The boy was a compound heterozygote for the c.90C > A and c.712G > A mutations of the insulin receptor gene, INSR, which are nonsense and missense mutations. In summary, we report the first Korean case of RMS, which was confirmed by two novel mutations of the INSR.

Atherosclerotic renal artery stenosis (RAS) usually involves the ostium and the proximal one-third of the renal artery main branch. Percutaneous renal artery angioplasty with stent placement is a well recognized treatment for atherosclerotic RAS. Occasionally, atherosclerotic RAS involves renal artery bifurcations. However, stent implantation in atherosclerotic RAS involving bifurcation is not only troublesome, but also challenging because of side branch occlusion and in-stent restenosis (ISR). In the present report, we describe the use of drug-eluting stents (DES) with provisional T-stenting technique for the treatment of renal artery bifurcation lesion. Follow-up angiogram showed no significant ISR 18 months after the procedure. In the treatment of renal bifurcation lesions, a two-stent strategy using DES could be a viable option in selected patients.

Spontaneous retroperitoneal hemorrhage is a distinct clinical entity that can present in the absence of specific underlying pathology or trauma and is typically associated with anticoagulation therapy. We report a case of a 74-year-old female patient with a cerebral infarction related to atrial fibrillation who developed a spontaneous lumbar arterial hemorrhage complicating heparin therapy. The diagnosis was suggested by a computed tomography scan and confirmed by angiography. She was treated successfully with transcatheter embolization.

Prolongation of QTc interval associated with Takotsubo cardiomyopathy (TC) has previously been reported in published case series. We report an unusual case of a patient who presented with TC associated with long-QT syndrome and developed cardiac arrest secondary to torsade de pointes. Since QT prolongation and bradycardia persisted after the resolution of TC, the patient received permanent pacemaker. Since then additional event did not occur. QT prolongation and bradycardia could be persistent even after recovery of TC, and permanent pacemaker insertion may be a treatment option of long QT syndrome related with TC.

Purpose

Long-term survivors of childhood cancer appear to have an increased risk for the metabolic syndrome, subsequent type 2 diabetes and cardiovascular disease in adulthood compared to healthy children. The purpose of this study was to investigate the frequency of the metabolic syndrome and associated factors in childhood cancer survivors at a single center in Korea.

Methods

We performed a retrospective review of medical records of 98 childhood cancer survivors who were diagnosed and completed anticancer treatment at Samsung Medical Center, Seoul, Korea between Jan. 1996 and Dec. 2007. Parameters of metabolic syndrome were evaluated between Jan. 2008 and Dec. 2009. Clinical and biochemical findings including body fat percentage were analyzed.

Results

A total of 19 (19.4%) patients had the metabolic syndrome. The median body fat percentage was 31.5%. The body mass index and waist circumference were positively correlated with the cranial irradiation dose (r=0.38, P<0.001 and r=0.44, P<0.00, respectively). Sixty-one (62.2%) patients had at least one abnormal lipid value. The triglyceride showed significant positive correlation with the body fat percentage (r=0.26, P=0.03). The high density lipoprotein cholesterol showed significant negative correlation with the percent body fat (r=-0.26, P=0.03).

Conclusion

Childhood cancer survivors should have thorough metabolic evaluation including measurement of body fat percentage even if they are not obese. A better understanding of the determinants of the metabolic syndrome during adolescence might provide preventive interventions for improving health outcomes in adulthood.

Purpose

Amylin secretion is increased parallel to insulin in obese subjects. Despite their marked obesity, a state of relative hypoinsulinemia occurs in children with Prader-Willi syndrome (PWS). Based on the hypothesis that amylin levels may be relatively low in PWS children, contributing to their excessive appetite, we studied amylin levels after oral glucose loading in children with PWS and overweight controls.

Materials and Methods

Plasma levels of amylin, glucagon, insulin, and glucose were measured at 0, 30, 60, 90, and 120 min after a glucose challenge in children with PWS (n = 18) and overweight controls (n = 25); the relationships among the variables were investigated in these two groups.

Results

Amylin levels were significantly correlated with insulin during fasting and during the oral glucose tolerance test in both groups. Amylin levels between 0 and 60 min after glucose loading were statistically different between the two groups. They were lower in children with PWS than in the controls between 0 and 30 min after glucose loading.

Conclusion

The relatively low levels of amylin, compared to those in overweight controls, during the early phase of glucose loading in patients with PWS, may contribute, in part, to the excessive appetite of PWS patients as compared to the overweight controls.

A single coronary artery (SCA) is a rare congenital anomaly of the coronary circulation, which is often associated with myocardial ischemia and other congenital cardiac anomalies. A 77-year-old woman visited our hospital complaining of typical chest pain. Coronary angiography revealed an isolated SCA. The right coronary artery did not originate from the aorta, but instead emerged from the distal left circumflex artery, with significant stenosis at the proximal portion of the left anterior descending artery. A stent was successfully implanted at the culprit lesion. There was no perfusion defect detected by a cardiac SPECT study.

Purpose

Prader-Willi syndrome (PWS) is a genetic disorder characterized by childhood-onset obesity and endocrine dysfunction that leads to cardiovascular disability. The objective of the study is to assess the relationship between carotid intima-media thickness (IMT) and atherosclerotic risk factors.

Materials and Methods

Twenty-seven PWS children and 24 normal controls were enrolled. Correlations of IMT with atherosclerotic risk factors were assessed.

Results

IMTs in the PWS group did not differ from those in the controls (p = 0.172), although total ghrelin levels were higher in the PWS children (p = 0.003). The multivariate analysis revealed positive correlations between total ghrelin levels (ρ = 0.489, p = 0.046) and IMT in the PWS group and between body mass index-standard deviation score (BMI-SDS) (ρ = 0.697, p = 0.005) and IMT in the controls.

Conclusion

Considering the positive correlation of IMT with total ghrelin levels and the high level of ghrelin in PWS children, a further study is warranted to evaluate the role of elevated ghrelin on atherosclerosis for PWS.

Background and Objectives

Left ventricular hypertrophy (LVH) is a major cardiovascular complication and an important predictor of mortality in patients with end stage renal disease. Some studies have shown that the serum aldosterone levels are correlated with LVH in non-diabetic patients undergoing hemodialysis. The objective of this study was to elucidate the relationships between serum biomarkers, including aldosterone, and echocardiographic findings, such as LVH, in patients on peritoneal dialysis.

Subjects and Methods

Thirty patients on continuous ambulatory peritoneal dialysis (CAPD) for >12 months at Soonchunhyang University Cheonan Hospital were included. Transthoracic echocardiography was performed and the left ventricular mass index (LVMI) was calculated using the Devereux formula. Serum biomarkers {N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T, C-reactive protein, renin, and aldosterone} were measured.

Results

Sixteen of 30 patients had LVH on the basis of the LVMI. The mean serum aldosterone level was 62.53±60.73 pg/mL (range, 5.03-250.68 pg/mL). LVH, on the basis of the LVMI, was not correlated with the serum aldosterone level. The serum aldosterone levels were not associated with echocardiographic findings, even with co-existing diabetes mellitus. The LVMI had a negative correlation with the hemoglobin (r=-0.405, p=0.029) and hematocrit (r=-0.374, p=0.042), and a positive correlation with NT-proBNP (r=0.560, p=0.002). The other biomarkers (renin, aldosterone, troponin T, and C-reactive protein) were not correlated with the LVMI. The LVMI was correlated with the left atrium volume index (r=0.675, p<0.001).

Conclusion

NT-proBNP is a good marker to predict LVH in patients undergoing CAPD. The serum aldosterone level is not correlated with LVMI, even with co-existing diabetes mellitus.

This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 µg/kg of GH once daily for 9 days; group 2, administered 200 µg/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.

A 63-year-old woman was diagnosed with ovarian cancer and peritoneal carcinomatosis. The day after paclitaxel was administered, an acute myocardial infarction occurred. Emergency coronary angiography revealed a filling defect in the left main coronary artery and total occlusion in the distal left anterior descending coronary artery, with no luminal irregularity or narrowing. Intravascular ultrasonography showed no significant plaque in the left main coronary artery. A thrombophilia work-up was negative, and the patient was treated with tirofiban, clopidogrel, and aspirin. The follow-up coronary angiogram showed that the occlusion of the distal obtuse marginal branch and distal left anterior descending artery had cleared. Paclitaxel has been associated with acute myocardial infarction. However, the pathogenesis of myocardial infarction associated with paclitaxel is not known. This case raises the possibility that paclitaxel can induce coronary artery thrombosis, resulting in myocardial infarction.

Background/Aims

The relationship between Helicobacter pylori infection and ghrelin is controversial. We compared ghrelin levels in gastric mucosa and plasma between H. pylori-positive and -negative subjects, and between before and after H. pylori eradication.

Methods

We compared the ghrelin levels in the antrum, body, and fundus between H. pylori-positive and -negative subjects; in stomach tissues between before and after H. pylori eradication; and in plasma and tissue in 10-person cohorts between before and after H. pylori eradication therapy. Body mass index, age, and sex were controlled for when comparing ghrelin levels.

Results

Stomach ghrelin levels (in the antrum, body, and fundus) did not differ significantly between H. pylori-positive and -negative samples (p=0.095, 0.316, and 0.897, respectively), or between before and after H. pylori eradication (p=0.19, 0.178, and 0.513, respectively). In the ten-person cohort study, plasma ghrelin levels in the eight H. pylori-positive subjects were 2,260 pg/mL (range, 1,280-3,770 pg/mL) and 1,900 pg/mL (range, 1,350-5,200 pg/mL) before and after eradication therapy (p=0.871). Stomach ghrelin levels did not differ significantly in the eight H. pylori-positive subjects between before and after H. pylori eradication (p=0.732, 0.618, and 0.435 in the antrum, body, and fundus, respectively), or between six eradicated and two noneradicated subjects (p=0.071, 0.857, 0.429, and 0.857 in the antrum, body, fundus, and plasma, respectively).

Conclusions

These results show that H. pylori infection has no effect on stomach ghrelin levels and that eradication therapy does not influence plasma or tissue ghrelin levels.

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86±0.15 to 0.58±0.12 ng/mL in the controls, and from 2.38±0.76 to 1.12±0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82±44.4 vs. -10.41±2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.

Purpose

Single-nucleotide polymorphism (SNP) markers within LIN28B have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP) or early puberty (EP). This study aimed to determine the frequency of putative genetic markers in girls with PP or EP.

Methods

Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of LIN28B, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage.

Results

Eleven SNPs in LIN28B were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, P=0.010). The trend that girls with non-AC haplotypes tended to have earlier puberty onset (P=0.037) was illustrated even in the EP+PP patient group by Kaplan-Meier analysis.

Conclusion

The results of the present study showed that non-AC haplotypes of LIN28B had a significant association with PP in girls.

Purpose

Continuous renal replacement therapy (CRRT) is becoming the treatment of choice for supporting critically ill pediatric patients. However, a few studies present have reported CRRT use and outcome in neonates weighing less than 3 kg. The aim of this study is to describe the clinical application, outcome, and complications of CRRT in small neonates.

Methods

A retrospective review was performed in 8 neonatal patients who underwent at least 24 hours of pumped venovenous CRRT at the Samsung Medical Center in Seoul, Korea, between March 2007 and July 2010. Data, including demographic characteristics, diagnosis, vital signs, medications, laboratory, and CRRT parameters were recorded.

Results

The data of 8 patients were analyzed. At the initiation of CRRT, the median age was 5 days (corrected age, 38+2 weeks to 23 days), and the median body weight was 2.73 kg (range, 2.60 to 2.98 kg). Sixty-two patient-days of therapy were reviewed; the median time for CRRT in each patient was 7.8 days (range, 1 to 37 days). Adverse events included electrolyte disturbances, catheter-related complications, and CRRT-related hypotension. The mean circuit functional survival was 13.9±8.6 hours. Overall, 4 patients (50%) survived; the other 4 patients, who developed multiorgan dysfunction syndrome, died.

Conclusion

The complications of CRRT in newborns are relatively high. However, the results of this study suggest that venovenous CRRT is feasible and effective in neonates weighing less than 3 kg under elaborate supportive care. Furthermore, for using potential benefit of CRRT in neonates, efforts are required for prolonging filter survival.

Purpose

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II.

Methods

We hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl-α-iduronate 2-sulphate.

Results

Plasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type (P=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 nmol·4 hr-1·mL-1. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; P=0.003).

Conclusion

These results show that the mild phenotype may be related to residual lysosomal enzyme activity.