Lopez et al. (2006) described a male infant, born of unrelated white parents, who presented with neonatal pneumonia and hypotonia. At age 3 months, he developed refractory left-sided seizures with secondary generalization, despite various combinations of antiepileptic drugs. ... Lopez et al. (2006) described a male infant, born of unrelated white parents, who presented with neonatal pneumonia and hypotonia. At age 3 months, he developed refractory left-sided seizures with secondary generalization, despite various combinations of antiepileptic drugs. He became progressively floppy and had difficulties feeding because of exhaustion. At age 7 months, severe episodic vomiting prompted duodenal tube feeding, and he rapidly developed widespread edema. Low serum albumin of 4.3 g/liter and massive proteinuria led to the diagnosis of nephrotic syndrome. Serum lactate was markedly elevated. The absence of purposeful gaze and visual evoked-potential responses, together with normal funduscopic findings, suggested cortical blindness. Brain MRI showed changes in the basal ganglia consistent with Leigh syndrome (256000). Muscle biopsy and fibroblasts showed primary coenzyme Q10 deficiency, as well as a defect in activity of mitochondrial complex II+III. Oral therapy with CoQ10 supplementation did not lead to clinical improvement. The patient died at age 8 months due to severe status epilepticus.
In an infant with a fatal encephalomyopathic form of CoQ10 deficiency with nephrotic syndrome, Lopez et al. (2006) found compound heterozygous mutations in the PDSS2 gene (610564.0001; 610564.0002), which encodes a subunit of decaprenyl diphosphate synthase, the first ... In an infant with a fatal encephalomyopathic form of CoQ10 deficiency with nephrotic syndrome, Lopez et al. (2006) found compound heterozygous mutations in the PDSS2 gene (610564.0001; 610564.0002), which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ10 biosynthetic pathway. Biochemical assays with radiolabeled substances indicated a severe defect in decaprenyl diphosphate synthase in the patient's fibroblasts. Each unaffected parent was heterozygous for 1 of the mutations.