Abstracts

Rationale: Coenzyme Q10 deficiency is a clinically and genetically heterogeneous syndrome which usually begins in childhood and manifests as seizures or cerebellar ataxia. Identification of Coenzyme Q10 deficiency is important because it is frequently reversible with treatment. Here, we report a boy who had a Coenzyme Q10 deficiency coexisting with a MCM4 mutation previously shown to be pathogenic. Methods: A retrospective chart review of this patient evaluated at our institution from April 2009 to April 2013 was conducted. Data obtained included demographics, clinical presentation, diagnostic procedures and subsequent treatment. Results: This 3-year-old Caucasian boy first presented with infantile spasms at 5 months of age with subsequent seizure disorder and developmental delay. At 3months, he was noted to be hypertonic and at 5 months he developed infantile spasms, which consisted of sudden brief flexion and release of the head and the upper extremities, 10-20 episodes/day. EEG showed hypsarrhythmia (Figure 1). No improvement in seizures even after anti-epileptic therapy with Topamax, Trileptal, Keppra and Ativan. He had a history of recurrent respiratory infections (5 episodes requiring inpatient stay) in the past 3 years. Plasma lactate, amino acids, Very Long Chain Fatty Acids, biotinidase, carbohydrate deficient transferrin, uric acid, acylcarnitine profile were examined and all found to be normal. Urine studies: organic acids, sulfocysteine, creatine/guanidinoacetate ratio were also done and were normal. Cerebrospinal Fluid (CSF) analysis of glucose, amino acids, lactic acid, neurotransmitter metabolites, biopterin/neopterin, methyltetrahydrofolate and pyridoxal 5 -phosphate levels were all normal. Genetic testing revealed an MCM4 gene mutation previously reported to cause developmental delay, NK cell deficiency, and adrenal insufficiency in an Irish family. Workup of adrenal insufficiency (adrenocorticotrophic hormone and cortisol levels) were all normal and lymphocyte differentiation tests also excluded NK Cell deficiency. Plasma Coenzyme Q10 levels were low, and muscle biopsy showed CoQ10 deficiency at 4.4 g/g (normal: 24-30). Genes known to cause Coenzyme Q10 deficiency, specifically APTX, CABC1, COQ2, PDSS1, PDSS2 were negative. Magnetic Resonance Spectroscopy (MRS) showed increased lactate levels in the brain (Figure 2). Whole exome sequencing revealed the MCM4 gene mutation that has been previously shown to be disease-causing. Coenzyme Q10 supplementation resulted in increased alertness and marked improvement in movement and tone. Conclusions: The presence of a MCM4 mutation does not rule out the possibility of the coexistence of a potentially treatable metabolic condition such as Coenzyme Q10 deficiency.