Sex: M
Vaccine: DTAP
Symptoms: Acoustic stimulation tests normal, Cytogenetic analysis abnormal, Dyskinesia, Dystonia, Encephalitis viral
Clinical narrative: Initial unsolicited report received from the literature on 07 Jun 2017. The following is verbatim from the article: Objective: To describe a 3 year old boy who presented at age 7 months with seizures and dystonia, in the setting of fever with novel compound heterozygous RMND1 mutations. Background: Mutations in RMND1, encoding RMND1 (required for nuclear meiosis division1), a mitochondrial protein of unknown function, have been reported in 20 patients presenting with early onset encephaloneuromyopathy, seizures, hearing impairment, nephropathy and early mortality. Laboratory studies have demonstrated decreased biochemical activities and levels of mitochondrial respiratory chain enzymes due to impaired mitochondrial Protein synthesis. Design/Methods: This child of nonconsanguineous parents developed normally until age 5 months, when he began to lose weight. At age 7 months, following DTAP, he developed a focal seizure with left arm and leg jerking and secondary generalization. Brain MRI showed focal diffusion restriction in the right frontotemporal regions. He was treated for presumed viral encephalitis. He had recurrent seizures, including infantile spasms, on multiple antiepileptic drugs and developed dystonia of the right leg. He also manifested psychomotor retardation. Hearing and renal functions have been normal, but he developed hyponatremia. Results: Whole exome sequencing in the patient revealed two novel mutations in RMND1: the missense mutation c.1316A greater than T (p.E439V) and the splice site mutation (c.6142T greater than C). The parents each carried one mutation. Sequencing of the cDNA from the patient skin fibroblasts uncovered an alternative transcript containing an inframe deletion of 6 nucleotides, resulting in the lack of two amino acids in the protein (D205A206del). The patient fibroblasts showed biochemical defects of the mitochondrial complex I, III and IV and defect of mitochondrial protein synthesis. Conclusions: Although our patient's fibroblasts manifested molecular and biochemical defects similar to those of other children with mutations in RMND1, the boy's clinical presentation differed from reported cases. This report confirms the clinical heterogeneity of RMND1 mutations and its importance in mitochondrial protein synthesis. This case involves a 7-month- old male patient who was vaccinated with a DIPHTHERIA, TETANUS AND ACELLULAR PERTUSSIS VACCINE (DTAP) (batch number, expiry date, dose, dose in series, route and site of administration was not reported) on an unknown date. It was reported that, this child of nonconsanguineous parents developed normally until age 5 months, when he began to lose weight. Concomitant medications were not reported. On an unknown date, following the vaccination, the patient developed a focal seizure with left arm and leg jerking and secondary generalization, recurrent seizures, including infantile spasms, on multiple antiepileptic drugs and developed dystonia of the right leg, he also manifested psychomotor retardation, hyponatremia. It was reported that, he was treated for presumed viral encephalitis. Relevant laboratory test results included brain MRI showed focal diffusion restriction in the right frontotemporal regions, Hearing and renal functions have been normal. Whole exome sequencing in the patient revealed two novel mutations in (required for nuclear meiosis division1) RMND1: the missense mutation c.1316A greater than T (p.E439V) and the splice site mutation (c.6142T greater than C). Sequencing of the cDNA from the patient skin fibroblasts uncovered an alternative transcript containing an inframe deletion of 6 nucleotides, resulting in the lack of two amino acids in the protein (D205A206del). The patient fibroblasts showed biochemical defects of the mitochondrial complex I, III and IV and defect of mitochondrial protein synthesis. The patient's other corrective treatment was not reported. The outcome of the events was not reported. Upon medical review, the case was considered as serious due to important medical event: secondary generalization. Documents held by sender: none.; Sender's Comments: Sanofi company comment dated 13-Jun-2017: In this case, the symptoms focal seizures, recurrent seizures, infantile spasms, leg jerking, Dystonia of the right leg and psychomotor retardation are consistent with diagnosis of Partial seizures with secondary generalization . Patient also experienced hyponatremia. The time to onset is compatible with the role of vaccine. Additional information regarding results of investigations (infectious work-up and cerebral work-up as EEG, MRI) ruling out alternative etiology, any seizure disorder, trauma, any infection, any trigger factor like hypocalcaemia, hypoglycemia or fever, vaccination and tolerance is needed to fully assess this case.