Case 2: A 2-month-old Girl with Liver Failure and a Brother with Tyrosinemia Type I

1. Galit Tal, MD* 2. Dalit E. Dar, PhD† 3. Shlomo Almashanu, PhD‡ 4. Stanley H. Korman, MBBS* 5. Elena Dumin, MD, PhD†,§ 1. *Metabolic Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel 2. †Department of Clinical Biochemistry, Rambam Health Care Campus, Haifa, Israel 3. ‡National Newborn Screening Program, Ministry of Health, Tel HaShomer, Israel 4. §Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel A 2-month-old girl presents with jaundice, pallor, and abdominal distention. She was born by normal delivery at term weighing 2,380 g. Her 22-month-old brother has tyrosinemia type I detected on newborn screening (NBS) and subsequently confirmed by the presence of succinylacetone on a urine organic acid analysis and demonstration of homozygosity for the IVS8-1(g-c) mutation in the FAH gene. He is doing well and has normal liver function on standard treatment with NTBC (nitisinone) and a tyrosine- and phenylalanine-restricted diet. The parents are first cousins of Christian Arab origin from the north of Israel and confirmed to be heterozygous for the FAH mutation. Prenatal genetic diagnosis performed in the latest pregnancy on chorionic villus sampling indicated that the girl is a heterozygous carrier for the FAH mutation. Findings from her NBS were completely normal, including a negative test for succinylacetone. She is being bottle-fed with a regular infant formula. On examination she looks pale and sweaty, although alert. Her abdomen is swollen but not tender, with a firm liver edge palpable below the costal margin, spleen not palpable. Initial laboratory results (Table) reveal a blood sugar level of 34 mg/dL (1.9 mmol/L), elevated hepatocellular and cholestatic liver enzyme levels, direct hyperbilirubinemia, hypoalbuminemia, and abnormal coagulation studies consistent with synthetic liver failure. She …