Volume 87 - 2024 - Fasc.2 - Case reports
Familial chylomicronemia syndrome: a novel mutation in the lipoprotein lipase gene
Familial chylomicronemia syndrome (FCS) (OMIM: 238600) is a rare autosomal recessive disease caused by a biallelic loss-of-function mutation in the lipoprotein lipase (LPL) complex which includes LPL and its co-factors. Patients with FCS have severe hypertiglyceridemia (> 2000 mg/dL). We describe a 15-month-old boy with repeated pancreatitis episodes caused by severe hypertriglyceridemia. Genetic analysis revealed a novel homozygous mutation in the LPL gene, i.e. c.626T>G; p.(Leu209*). The mutation, carried by both parents, has been classified as a type 4 mutation which is likely pathogenic. Treatment aims at decreasing hypertriglyceridaemia by a low-fat diet (< 20g/day) eventually supplemented with medium chain triglyceride (MCT) fat to ensure caloric intake. In 2019, volanesorsen was approved by the European Medicines Agency (EMA) as adjunct treatment for adult patients with genetically proven FCS and persisting episodes of pancreatitis despite the diet.
An acute ileocolitis of unexpected origin
The colon is a common site of primary malignancy. However, it is a
very rare metastatic localisation. Here, we report a case of a signet-ring
cell carcinoma of the stomach metastasizing to the ileum and colon,
mimicking a presentation of an acute inflammatory ileocolitis.
CYP2D6 polymorphism may contribute to Trazodone-induced hepatotoxicity: a rare case of drug-drug-gene induced liver injury
A 46-year-old female with a history of type I diabetes, alopecia areata and autoimmune hypothyroidism presented with a significant hepatocellular hepatitis. The top 3 differential diagnoses were drug-induced liver injury, autoimmune hepatitis and drug-induced autoimmune hepatitis. Considering the predisposition for immune-mediated conditions, we performed a liver biopsy to exclude an autoimmune hepatitis.
A temporal relationship between the onset of liver injury and the start of Trazodone and Escitalopram was observed. We report a case of Trazodone-induced liver injury in which pharmacogenomic testing identified a CYP2D6 gene polymorphism leading to CYP2D6 dysfunction and accumulation of Trazodone’s potential hepatotoxic metabolite m-CPP, which elucidates the underlying pathogenesis. This case also presents an example of a drug-drug-gene interaction between Trazodone and the not-so-innocent bystander Escitalopram leading to an additional component of CYP2D6 inhibition.
This case highlights the potential benefit of targeted pharma-cogenomic testing to minimise the risk of drug-induced liver injury.
Respiratory failure in a tofacitinib treated patient with ulcerative colitis
Tofacitinib is an oral Janus Kinase (JAK) inhibitor recently approved for the management of moderate to severe ulcerative colitis (UC). Safety data on tofacitinib has suggested a moderately increased risk for venous thromboembolism (VTE) as well as non-opportunistic infections and non-infectious drug-related lung disease. We faced a diagnostic dilemma between an infectious and non-infectious cause of acute respiratory insufficiency in a patient on recent tofacitinib therapy. A lung CT scan showed bilateral interstitial pneumonic infiltrates and a PCR on bronchoalveolar lavage fluid was positive for cytomegalovirus (CMV). The patient’s condition improved after discontinuation of tofacitinib and treatment with anti-viral drugs and high dose corticosteroids. A CMV primary infection was suspected, however a drug-induced interstitial lung disease cannot be excluded in the differential diagnosis of patients with autoimmune disorders under tofacitinib therapy who present with fever, hypoxia and pulmonary infiltrates.
