Case Conference 내분비 대사 내과 R2 맹치훈

: 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 남동우 M/24 입원일 –

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

√ 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 (-)

√ 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 (-/-)

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 (-/-)

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

√ Impression Metabolic encephalopathy R/O Viral encephalitis

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

√ Laboratory finding CBC/DC 6830/mm g/dL % /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

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 F/U ( 6AM) ammonia 66 ug/dL  slightly improved mentality : Stupor Spontaneous eye open, pain reaction (+), Corneal reflex (+/+) ABGA – 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

~ 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 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

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 Liver biopsy Transfer to dep. Hepatology Mental status – no interval change : alertness Continued lactulose enema

√ Liver biopsy (05.3.3)

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

√ Urea biosynthesis Mitochondria Cytoplasm

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

Plasma Aminoacid analysis

Urine Aminoacid analysis

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 ??

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

? Unsolved problems Severe hypernatremia ? [since 2. 26] - d/t persistent lactulose enema or osmotic diuresis ? - elevated BUN/Cr level - balanced Intake/Output during ICU admission Hypertriglyceridemia ? 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 Cause of Beta-aminoisobutyric aciduria? Molecular genetic test - Mutations in SLC25A13 on Chromosome 7q21.3- Citrullinemia type 2 - Mutation on ASS(Arginiosuccinate synthetase)- Citrullinemia type 1