P.369 - Multi-system disorder and severe recurrent rhabdomyolysis due to TANGO2 mutations in a 3 year-old child

Abstract

Recessive mutations in TANGO2 result in a rare genetic cause of severe recurrent rhabdomyolysis (RM) associated with encephalopathy and cardiomyopathy. A 3-year-old boy was referred for genetic investigations following two extremely severe RM episodes requiring intensive care unit admissions. The first episode occurred at 13 months most probably triggered by a throat infection and dehydration (CK increase: Day 1: 1,400 IU/L, Day 1 (night): 103,000 IU/L, Day 2: 177,000 IU/L and Day 3: 210,000 IU/L). He received treatment for mild hypothyroidism and steroids on Day 4. Complications included hyponatraemia with comatose state, nosocomial bacterial infection and heart failure. In the period between the first and the second hospitalization, he slowly regained muscle tone and started crawling at 18 months of age. The second RM episode occurred at 27 months following a viral infection, serum CK peaked at 225,000 IU/L, decreasing over 4 weeks (147 IU/L). Previous medical history included psychomotor delay. Brain MRI showed moderate enlargement of ventricles and bilateral frontotemporal subarachnoid spaces, mild hypomyelination and reduced thickness of the corpus callosum. Normal investigations included respiratory chain enzymes in muscle tissue, urine organic acids, acylcarnitine profile, urine and plasma amino acidogram and s-Ab anti myositis specific (immunblotting). WES confirmed compound heterozygous mutations in TANGO2 in the proband and in his asymptomatic sister (16 months), which were inherited from both parents (nonsense p.Arg88*, p.Glu112fs frameshift). Following the genetic diagnosis, the patient has been regularly monitored by a multidisciplinary team. The compound heterozygous TANGO2 mutations point to a virtually complete functional knock-out of the TANGO2 protein in the proband. Looking for recessive mutations in TANGO2 should be considered in young children presenting with a combination of psychomotor delay, hypothyroidism, cardiomyopathy and RM.