Table 2.

Overview of patients treated with N-carbamylglutamate at the University Hospital of Padova.

Patient	Overview
1(PA)	• 20-year-old male with developmental delay, born at term after an uncomplicated pregnancy, labour and delivery
• Patient presented with severe metabolic acidosis in the first days of life associated with hyperammonaemia and hyperglycinaemia, leading to a diagnosis of PA confirmed by organic acid analysis
• A protein-restricted diet with amino acids supplementation, carnitine was initiated
• Clinical course characterised by frequent and severe episodes of decompensation, mostly requiring hospital admission for intravenous fluid therapy
• Patient more stable since adolescence, but in last 3 years developed stable dilated cardiomyopathy, with ammonia levels of 80-140 μmol/l
• Following an episode of vomiting with food refusal, mild hyperammonaemia and acidosis requiring hospitalisation 13 months ago, patient initiated on NCG therapy, 50 mg/kg/day
2(PA)	• 11-year-old male, born at term
• Patient presented with acute metabolic acidosis and hyperammonaemia at 5 days old
• Treated with a low protein diet, amino acid mixture and carnitine, which brought progressive clinical improvement
• Frequent mild to moderate episodes of metabolic acidosis over disease course, with ammonia levels of 80-120 μmol/l
• After a prolonged period of constipation, with plasma ammonia at 100 μmol/l, patient initiated on NCG therapy, 50 mg/kg/day
3(PA)	• 9-year-old sister of patient 2, diagnosed with propionic aciduria at birth as a result of her affected brother, therefore avoiding any decompensation episodes
• A low protein diet and carnitine was initiated
• At the age of 3 years she had meningitis with severe metabolic decompensation and hyperammonaemia requiring haemodialysis and severe neurological impairment
• Several subsequent hospital admissions, primarily for food refusal, persistent vomiting with ketosis and hyperammonaemia (up to 200 μmol/l); after her last episode (13 months ago) patient initiated on NCG therapy, 50 mg/kg/day
4(PA)	• 3-year-old male, born at term after an uncomplicated pregnancy, labour and delivery
• Patient presented with severe hyperammonaemia and metabolic acidosis that required haemodialysis
• Diagnosed with PA by organic acid analysis, and started treatment with a low protein diet with amino acids supplementation and carnitine
• Multiple hospital admissions during first two years of life, typically for acute exacerbations due to catabolic states, during which his plasma ammonia level rose up to 200 μmol/l
• Following a severe episode with persistent hyperammonaemia (160 μmol/l) 14 months ago, patient initiated on NCG therapy, 50 mg/kg/day
5 (MMA)	• 12-year-old female who presented at birth with metabolic decompensation and hyperammonaemia (400 μmol/l) requiring haemodialysis and ventilation support
• Medical history characterised by progressive clinical deterioration with increasing episodes of vomiting, acidosis and loss of appetite
• Patient’s kidney function fluctuated over the years, but she has not required dialysis
• Owing to persistent mild acidosis and ammonia level of around 100 μmol/l, patient initiated on NCG therapy, 50 mg/kg/day
6 (MMA)	• 6-year-old female with slight mental retardation, who presented at the age of 11 months, after an episode of gastroenteritis, with severe metabolic acidosis and hyperammonaemia requiring haemodialysis and ventilation
• Responded well to a protein-restricted diet supplemented with carnitine but not to vitamin B12
• Patient suffering with frequent episodes of metabolic acidosis and hyperammonaemia some of these requiring admission to the ICU; complicated with severe basal ganglia damage
• Patient initiated on NCG therapy, 50 mg/kg/day
7 (MMA)	• 2-year-old male who presented with metabolic acidosis and severe hyperammonaemia in the first days of life, requiring haemodialysis and ventilator support
• Vomiting and poor feeding were present in the first months of life, despite a gastrostomy, requiring multiple admissions for intravenous fluids
• Hyperammonaemia was always present during metabolic acidosis. He also has kidney failure
• Following a recent admission (6 months ago) patient was initiated on NCG therapy, 50 mg/kg/day
8 (MMA)	• 12-year-old female who presented with neonatal metabolic acidosis and hyperammonaemia requiring therapy and intubation in ICU
• Patient began treatment with a protein-restricted diet with amino acids mixture and carnitine
• In the first years of life, she had several episodes of metabolic decompensation with hyperammonaemia (< 100 μmol/l) and vomiting requiring intravenous fluid therapy. Two years ago she presented with severe dystonia episodes refractory to pharmacological treatment, which required subthalamic deep brain stimulation
• Patient required hospitalisation owing to food refusal and frequent vomiting prior to NCG treatment; despite fluid treatment and a low protein diet her ammonia levels increased to 140 μmol/l
• Five months ago, patient was initiated on NCG therapy, 50 mg/kg/day

ICU, intensive care unit; MMA, methylmalonic aciduria; NCG, N-carbamylglutamate; PA, propionic aciduria.