High-dose methotrexate-induced reversible grade 4 hyperbilirubinaemia and transaminitis in an adolescent with Burkitt Leukaemia.

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.

Dual mutation (MTHFR A1298C with PAI (4G) mutation) manifesting with bilateral lower limb gangrene in a neonate.

Neonates are at highest risk of thrombosis among paediatric patients. The relative prothrombotic state in a well neonate is compensated by other factors preventing spontaneous thrombosis; however, in a neonate with genetic predisposition, the balance is tilted predisposing them to a life-threatening thrombotic episode. We describe a rare case of methylenetetrahydrofolate reductase A1298C (homozygous) mutation along with plasminogen activator inhibitor (4G) mutation in a neonate who developed bilateral lower limb gangrene following thrombosis of the iliac vessels without any triggering factor. The neonate underwent thrombectomy as debulking measure along with thrombolytic therapy followed by unfractionated heparin and low-molecular-weight heparin which is still being continued along with oral aspirin. The neonate had to undergo amputation of both the involved lower limbs in view of dry gangrene. This case highlights that the dual mutations causing the prothrombotic state predispose the individual to the spontaneous life-threatening thrombotic episode as compared with the single mutation.