Col Rama Krishna Sanjeev Military Hospital Chennai Prof Shanmughasundaram Mehta Hospital, Chennai

Col Rama Krishna Sanjeev Military Hospital Chennai Prof Shanmughasundaram Mehta Hospital, Chennai

11 day old male neonate admitted on 26/6 to our Hospital with c/olethargy -since day1 abnormal movements - since day1 Poor feeding -since day1

21 year old 2nd gravida,2nd degree consanguinous marriage Uneventful antenatal period Booked case Routine antenatal evaluation did not suggest any abnormality

1st issue had cyanosis soon after delivery by LSCS (ind- polyhydramnios with non progress of labour) at MH. Had neonatal seizures. Diagnosed to have PPHN. Was oxygen dependent & had repeated seizures in early infancy. Developed HIE(MRI showed sequelae) & expired at 8 months of age.

Day 1 born by LSCS (Indication-previous LSCS) after uneventful antenatal period Cried after birth with normal APGAR scores Wt-2.8 kg. Within few hours had refusal to feed Within 12 hours had multifocal seizures,loaded with iv Phenobarbitone.

Day 2-12Treated with IV Fluids, antibiotics, IV Phenobarbitone, after full metabolic & septic workup in Dr Mehta Hospital. Seizures improved & nasogastric feeds were tolerated. Had hypomagnesemia & hypocalcemia requiring correction.

Required phototherapy for jaundice on days 46 Persistence of abnormal posturing, hyporeflexia & increased tone prompted search for IEM.

Wt- 2.7 kg OFC- 34 cm No pallor, icterus. Pink on air.spo2 96% Vitals normal Per abdomen- liver 2cm palpable CNS- lying quietly, frog s leg posturing, hypotonia presents

CBC NAD Urinary metabolic screen for aminoacids, carbohydrates, MPS, porphyrins, organic acids & ketones WNL. USG & MRI cranium WNL Echo-WNL EEG abnormal with spike & sharp waves predominance to the left side. ABG normal

Neonatal screen for TORCH, congenital hypothyroidism, galactosemia, cystic fibrosis & G6 PD negative Metabolic workup showed hypocalcemia(7.8 mg%), hypomagnesemia (1.6 mg%) & hyperbilirubinemia ( 15mg%). Mildly raised ammonia 59 µmol/l & 65 µmol/l CSF study, blood cultures were non contributory CRP -negative

12 day old male neonate with uneventful maternal antenatal period & h/o seizures, poor feeding from day 1.Managed with iv fluids, antibiotics, with persistence of lethargy, hypotonia & poor feeding. h/o 2nd degree parental consanguinity with death of previous sibling in infancy following PPHN & HIE.

CBC WNL TMS- received on 29/6/11 showed moderately elevated Ornithine with normal Carnitine profile. Advised to do ammonia levels. Ornithine -192.74µM(4-85) with advise to furthur work up for plasma ammonia estimation.

Sodium benzoate -200mg in 20 ml of 10% dextrose given 12 hourly orally Seizures continued Initially feeds restricted & iv fluids given Feeds reintroduced gradually Abnormal movements decreased to nil & feeds reintroduced. Sodium benzoate stepped up to 125 mg 6hourly Abnormal movements reappeared

Abnormal movements increased with appearance of apnea, twitching movements of the eyes. Developed gasping with bradycardia following a spell of apnea. Ventilated, iv Mannitol, iv Magsulph, sodium benzoate continued. Developed airway bleeding & transfused Vasopressors added Neonate expired on day 21.

1 in 80000 deliveries X linked disorder Clinical features- males affected either early or late. Early form is rapidly fatal due to hyperammonemia unless intervened. Lethargy, hypotonia, seizures, hypothermia, poor appetite. Hyperammonemia can be rapidly fatal due to rapid development of cerebral edema. Mental retardation, headaches with protein intake may be seen in the late onset disease.

Management protein restriction/ iv fluids with dextrose/dialysis/ prevent catabolism by providing adequate carbohydrates & lipids/ use of IV Arginine/ sodium benzoate -both iv( with phenyacetate) & oral. Liver transplant is curative & prevents hyperammonemia induced brain damage. Single biggest hurdle to diagnosis is lack of clinical suspicion.

High Ammonia Exclude clinically recognizable causes Prematurity, Valproate, Liver disease, Reye s Initiate treatment & and evaluate further. Do ABG Acidosis No Acidosis Organic Acidemia Urea Cycle Disorder Elevated Citrulline Citrullinemia (>1000) Arginino succinic acidosis (100-300) Absent Citrulline OTS deficiency CPS deficiency 19

Demonstrated lower concentrations of Arginine & Citrulline in neonates with PPHN N Engl J Med 2001;344(24):1832 1838. Lower concentration of Arginine & Citrulline in neonates with OTC deficiency. Lower NO production when demand for it is high in the neonatal period. Leads to PPHN Since previous issue was male & OTC is an X linked disorder both may have had same heritable illness

Genetic diagnosis available Male vs female Counselling to mother

Col ( Dr) RG Holla (retd) Consultant Neonatologist, Fortis Hospital, New Delhi Dr Rahul Yadav Consultant Neonatologist, CHILDS Trust Hospital, Chennai Dr Thangavelu, Mehta Hospital, Chennai Col Rama Krishna Sanjeev Paediatrician Military Hospital rksanjeev88@yahoo.com 9445007498

Thank you