We report a one-day-old Korean boy with 2-Methylbutyryl-CoA dehydrogenase(2-MBCDase) deficiency detected by urine organic acid and acylglycine analysis, plasma acylcarnitine analysis and confirmed by enzyme assay and Western blot. The patient was born at 35 weeks and three days with oligohydroamnios and premature rupture of membrane for 31 hours, as a second child of healthy non-consanguineous parents. There was no significant family history and spontaneous abortion. He was admitted at NICU under ventilator care due to prematurity, respiratory difficulty, and decreased generalized muscle tone. During the first week of hospitalization, he presented with disseminated intravascular coagulation and sepsis. A grade IV intraventricular hemorrhage on brain sonography was observed on the 7th day after birth with seizure. The clinical course of aggravation and recovery was repeated for one month. In laboratory tests, blood C5-acylcarnitines(isovaleryl/ methylbutyrylcarnitine) and urine 2-methylbutyrylglycine(2-MBG) were markedly elevated; butyrylglycine and isobutyrylglycine were also detected in small amounts in the urine. SBCAD(short branched-chain acyl-CoA dehydrogenase) enzyme activity was undetectable in cultured skin fibroblasts and Western blot showed no detectable immuno-reactive protein. Molecular analysis of the 2-MBCD gene revealed a polymorphism in the leader peptide region(38G>A; Arg13Lys) and homozygous for a non-coding polymorphism 639T>C. This is the first such case in Korea. This disorder is known to be relatively common in one other oriental ethnic group, the Hmong. The baby has been fed on a maple syrup urine disease(MSUD)-similar diet program, and is still alive and is 26-months-old now. However, he developed significant neurologic complications including communicating hydrocephalus, cerebral palsy, and blindness. Presumably the prematurity and its complications may also attribute to his severe neurologic problems. However, the clinical course was particularly severe, a finding in contrast with the observation from several asymptomatic Hmong cases. The clinical course of 2-MBCDase deficiency could be very variable and careful monitoring and follow up should be considered.
Abortion, Spontaneous ; Acer ; Blindness ; Blotting, Western ; Brain ; Cerebral Palsy ; Child ; Diet ; Disseminated Intravascular Coagulation ; Enzyme Assays ; Ethnic Groups ; Female ; Fibroblasts ; Follow-Up Studies ; Hematologic Tests ; Hemorrhage ; Hospitalization ; Humans ; Hydrocephalus ; Korea ; Male ; Membranes ; Oxidoreductases* ; Parents ; Parturition ; Plasma ; Pregnancy ; Protein Sorting Signals ; Rupture ; Seizures ; Sepsis ; Skin ; Ventilators, Mechanical

Previously we demonstrated that ATP released from LPS-activated microglia induced IL-10 expression in a process involving P2 receptors, in an autocrine fashion. Therefore, in the present study we sought to determine which subtype of P2 receptor was responsible for the modulation of IL-10 expression in ATP-stimulated microglia. We found that the patterns of IL-10 production were dose-dependent (1, 10, 100, 1,000 micrometer) and bell-shaped. The concentrations of ATP, ATP-gammaS, ADP, and ADP-beta S that showed maximal IL-10 release were 100, 10, 100, and 100 micrometer respectively. The rank order of agonist potency for IL-10 production was 2'-3'-O-(4-benzoyl)-benzoyl ATP (BzATP) = dATP > 2-methylthio-ADP (2-meSADP). On the other hand, 2-methylthio-ATP (2-meSATP), alpha,beta-methylene ATP (alpha,beta-meATP), UTP, and UDP did not induce the release of IL-10 from microglia. Further, we obtained evidence of crosstalk between P2 receptors, in a situation where intracellular Ca2+ release and/or cAMP-activated PKA were the main contributors to extracellular ATP-(or ADP)-mediated IL-10 expression, and IL-10 production was down- regulated by either MRS2179 (a P2Y1 antagonist) or 5'-AMPS (a P2Y11 antagonist), indicating that both the P2Y1 and P2Y11 receptors are major receptors involved in IL-10 expression. In addition, we found that inhibition of IL-10 production by high concentrations of ATP-gammaS (100 micrometer) was restored by TNP-ATP (an antagonist of the P2X1, P2X3, and P2X4 receptors), and that IL-10 production by 2-meSADP was restored by 2meSAMP (a P2Y12 receptor antagonist) or pertusis toxin (PTX; a Gi protein inhibitor), indicating that the P2X1, P2X3, P2X4 receptor group, or the P2Y12 receptor, negatively modulate the P2Y11 receptor or the P2Y1 receptor, respectively.
Adenosine Diphosphate/analogs & derivatives/pharmacology ; Adenosine Triphosphate/analogs & derivatives/*pharmacology ; Adenylate Cyclase/antagonists & inhibitors ; Animals ; Calcium/metabolism ; Chelating Agents/pharmacology ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Enzyme Inhibitors/pharmacology ; Extracellular Space/drug effects/*metabolism ; Gene Expression Regulation/drug effects ; Interleukin-10/*biosynthesis ; Microglia/*drug effects/enzymology/*metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor Cross-Talk/*drug effects ; Receptors, Purinergic P2/agonists/antagonists & inhibitors/genetics/*metabolism ; Thionucleotides/pharmacology

Harlequin syndrome, which is a rare disorder caused by dysfunction of the autonomic system, manifests as asymmetric facial flushing and sweating in response to heat, exercise, or emotional factors. The syndrome may be primary (idiopathic) with a benign course, or can occur secondary to structural abnormalities or iatrogenic factors. The precise mechanism underlying idiopathic harlequin syndrome remains unclear. Here, we describe a case of a 6-year-old boy who reported left hemifacial flushing and sweating after exercise. He had an unremarkable birth history and no significant medical history. Complete ophthalmological and neurological examinations were performed, and no other abnormalities were identified. Magnetic resonance imaging was performed to exclude lesions of the cerebrum and cervicothoracic spinal cord, and no abnormalities were noted. His final diagnosis was classic idiopathic harlequin syndrome. Herein, we report the first pediatric case of idiopathic harlequin syndrome in Korea.
Cerebrum ; Child ; Diagnosis ; Flushing ; Hot Temperature ; Humans ; Korea ; Magnetic Resonance Imaging ; Male ; Neurologic Examination ; Pediatrics ; Reproductive History ; Spinal Cord ; Sweat ; Sweating