1. Case Conference 내분비 대사 내과 R2 맹치훈

2. : 주소 : 의식변화 o/s : 내원 2 일 전 현병력 - 평소 특이병력 없이 지내던 환자로 내원 20 일 전 부터 nausea 호소하여 개 인의원에서 gastroscopy 시행했던 병력 있으며 (gastroscopy 결과 - esophageal erosion) 그 후에도 계속 nausea 호소해옴 - 내원 약 일주일 전, 일시적으로 자신이 한 말과 행동을 잘 기억하지 못하는 증상이 한 차례 있었으며 그 후 내원 2 일 전 아침에 의식 저하 되면서 부모가 물어도 대답을 잘 못하는 등의 모습 보여 성바오로 병원 입원함 - 성 바오로 병원에서 시행한 생화학 검사에서 ammonia 130 ug/dL 측정되었 으며 lactulose enema 1 회 시행 후 60 ug/dL 로 호전되었으며 further evaluation 위하여 본원으로 전원되어 신경과로 입원함 11760553 남동우 M/24 입원일 – 05. 2. 22

3. 과거력 - DM (-) HTN (-) Tb (-) Hepatits (-) - Op (-) 가족력 개인력 : Alcohol (-) Smoking (-)

4. √ Review of system General : fatigue (-) fever (-) chills (-) weight loss (-) Skin : rash (-) pigmentation (-) itching (-) Head & Neck : headache (-) trauma (-) stiffness (-) Eye / ENT : sore throat (-) dry mouth (-) hoarseness (-) Respiratory : cough (-) sputum (-) dyspnea (-) Cardiac : palpitation (-) orthopnea (-) chest discomfort (-) Gastrointestinal : A/N/V/D/C (-/-/-/-/-) abdominal pain (-) Genitourinary : urgency (-) frequency (-) polyuria (-) Endocrine : polydipsia (-) heat intolerance (-) Musculoskeletal : musle weakness (-) arthralgia (-) Neurology : paralysis (-) sensory change (-)

5. √ Physical examination Vital sign : 130/80 mmHg-113 회 /min-20 회 /min-36.8°C Height 178 cm Body weight 66 kg BMI 20.8 kg/m 2 General apperance alert conciousness not so ill appearance Skin no rash or pigmentation, skin turgor : normal Head & Neck no neck vein engoregement no cervical / supraclavicular LN enlargemen Eye & ENT isocoric pupil with PLR(+/+) pinkish conjunctiva whitish sclera Pharyngeal injection(-) paratonsilar hypertrophy (-/-)

6. Thorax symmetric chest expansion clear breathing sound without crackle regular heart beat without murmur Abdomen soft and flat abdomen normoactive bowel sound no hepatosplenomegaly no tenderness no rebound tenderness Back / Extremity CVA tenderness (-/-) pretibial pitting edema (-/-)

7. Neurologic examination - alert mentality - higher cortical function : time, place, person – intact - calculation : intact - language : reading, writing, comprehension, naming – intact - Cranial nerve system : facial palsy (-) isocoric pupil with PLR (++/++) nystagmus (-) hearing intact, gag reflex intact - Motor Sensory : all modality intact - DTR : all intact - cerebellar function test : finger to nose / finger to finger (-/-) vv vv

8. √ Impression Metabolic encephalopathy R/O Viral encephalitis

9. √ Diagnostic plan CBC/DC and routine chemistry CSF Study - Pressure, cell count, chemistry, microbiological culture Serology for viral infection Brain imaging study EEG

10. √ Laboratory finding CBC/DC 6830/mm3 -14.4 g/dL- 39.1 % - 192000/mm 3 Chemistry TB/DB 1.3/0.3 mg/dL ALP 78 U/L LD 531 U/L Prot/Alb 6.2/3.9 g/dL AST/ALT 44/63 U/L BUN/Cr 11/0.7 mg/dL Na/K/Cl 132/3.7/102 mmol/L CRP 0.0 mg/dL ESR 5 mm/hr EEG - Unremarkable CSF examination Pressure 22 cmH2O RBC 1/mm 3 WBC 1/mm3 Protein 100 mg/dL Glucose 76 mg/dL

11. AM 4:00  Semicomatous mentality AST/ALT 62/58 U/L Ammonia 537 ug/dL  Lactulose enema q 1hr No significant interval change of mental status Brain CT : Unremarkable Abdominal US : No specific abnormality F/U EEG : diffuse cerebral dysfunction 2005. 2. 24 F/U ( 6AM) ammonia 66 ug/dL  slightly improved mentality : Stupor Spontaneous eye open, pain reaction (+), Corneal reflex (+/+) ABGA 7.402 – 30.7 mmHg – 85.5 mmHg – 18.7 mmol/L – 97.0 % Recurrent elevation of ammonia level : (AM11) 259 – (PM5) 448 ug/dL  Newly established impression – Metabolic encephalopathy d/t hyperammonemia 2005. 2. 25

12. 2005. 2. 26 ~ 2. 27 Continue lactulose enema q 1hr F/U Ammonia elevation upto 1125 ug/dL  158 ug/dL (2. 27, PM7) Impreoved mental status - Mental alert (2. 27, PM 7) Electrolytes imbalence Na/K/Cl 165/2.6/139 mmol/L BUN/Cr 35/1.4 mg/dL AST 524 U/L rGT 131 U/L LD 1354 U/L TG 181 mg/dL 2005. 2. 28 F/U Lab Result Na/K/Cl 159/2.8/130 mmol/L BUN/Cr 28/1.0 mg/dL AST/ALT 104/198 U/L rGT 97 U/L LD 875 U/L TG 306 mg/dL CK 1225 U/L Myoglobin 335 ng/ml Spot Urine – Na 13 mmol/L K 23.7 mmol/L Cl 72 mmol/L

13. 2005. 3. 1 Mental status : alert Lab F/U Na/K/Cl 146/3.1/116 mmol/L BUN/Cr 19/0.9 mg/dL AST/ALT 125/203 U/L rGT 91 U/L LD 1021 U/L CK 1318 U/L Myoglobin 138 ng/ml Ammonia 129 ug/dL ALP 94 U/L 2005. 3. 3 Liver biopsy Transfer to dep. Hepatology Mental status – no interval change : alertness Continued lactulose enema

14. √ Liver biopsy (05.3.3)

15. Possible etiology - Defects in the Urea cycle - Secondary hyperammonemia due to Organic acidemia - Reye syndrome ? Metabolic encephalopathy due to hyperammonemia

16. √ Urea biosynthesis 1 2 3 4 5 Mitochondria Cytoplasm

17. Impression - Organic acidosis with increased anion gap - Reye syndrome - Hyperammonemia type 1 or 2 - Citruillinemia type 1 or 2 - Argininosuccicaciduria - Hyperarginemia Diagnostic plan - Urine Organic acid analysis & ABGA - Urine Orotic acid level - Plasma aminoacid analysis - Specific enzyme assay related with ammonia metabolism(Urea cylce) Metabolic encephalopathy due to hyperammonemia Urea cycle defect

18. 286 735 Plasma Aminoacid analysis

19. Urine Aminoacid analysis 890 867 690

20. Citrullinemia Glutaminemia Beta-aminoisobutyric aciduria Citrullinemia - Type 1 : neonatal form – Argininosuccinate synthetase deficiency milder late-onset form - Type 2 : more milder form - citrin deficiency Glutaminemia - probably reflect enhanced glutamine synthesis consequent to elevated tissue ammonia level Beta-aminoisobutyric aciduria d/t thymine catabolism ??

21. Urine orotic acid : NEGATIVE ABGA : 7.397 – 33.4 mmHg – 105.1 mmHg – 20.1 mmol/L – 97.7 % 1.Citrullinemia type 1 : Late – onset form 2.Citrullinemia type 2 : Citrin deficiency  FINAL DIAGNOSIS

22. ? Unsolved problems 1. 1. Severe hypernatremia ? [since 2. 26] - d/t persistent lactulose enema or osmotic diuresis ? - elevated BUN/Cr level - balanced Intake/Output during ICU admission 2. 2. Hypertriglyceridemia ? - 265 mg/dL at adm(2.24)  306 mg/dL (2.28)  1430 mg/dL at discharge (3.17) - not evaluated other lipid profile except initial HDL/LDL 32/76 mg/dL 3. 3. Cause of Beta-aminoisobutyric aciduria? 4. 4. Molecular genetic test - Mutations in SLC25A13 on Chromosome 7q21.3- Citrullinemia type 2 - Mutation on ASS(Arginiosuccinate synthetase)- Citrullinemia type 1