Case Quiz  (November 2017)

A 33-month-old boy, born after an uneventful pregnancy. The parents were first cousins. At 2 months, nystagmus was noted. At 12 months, the boy developed generalized edema (urine protein: creatinine ratio was 14). He was diagnosed as nephrotic syndrome and was treated with steroids. There was no response to steroids and cyclosporine was commenced . A renal biopsy specimen revealed focal and segmental glomerulosclerosis. Mutation analyses of the nephrin (NPHS2) and podocin (NPHS1) genes were negative.

Neurologic examination showed hypotonia and mild psychomotor delay. Plasma creatine kinase (CK) and lactate, brain MRI, echocardiography, and brainstem auditory evoked potentials were normal. Funduscopic examination showed optic atrophy. Visual evoked potentials showed altered retinocortical transmission, and the electroretinogram suggested rod-cone retinopathy.

Renal function worsened: serum creatinine levels rose from 0.8 mg/dl at 12 months to 5.2 mg/dl at 18 months, and the child required peritoneal dialysis.

At 18 months, he developed frequent vomiting, psychomotor regression, tremor, and weakness; he lost the ability to walk and stand unassisted. He also developed status epilepticus, with focal EEG abnormalities, especially in the left occipital region. Blood CK and lactate levels remained normal; CSF lactate, serum amino acids, and urinary organic acids were also normal. Brain MRI showed diffuse cerebral atrophy, mild cerebellar atrophy, and bilateral lesions in the cingulate cortex and subcortical area . He had multiple seizures unresponsive to phenobarbital. At 22 months, he developed right hemiplegia with myoclonus and swallowing difficulties. A muscle biopsy was performed.

Case Answer (November  2017)

Primary CoQ10 deficiency is inherited as an autosomal recessive trait and has been associated with three main clinical phenotypes:
1. A predominantly myopathic form is characterized by recurrent myoglobinuria and CNS involvement with seizures, ataxia, or mental retardation.
2. A more common ataxic variant is dominated by ataxia and cerebellar atrophy, with varying involvement of the CNS, peripheral nerves, and muscle.
3. A third variant presents as an infantile encephalomyopathy with multisystemic involvement.

CoQ10 is vital for mitochondrial energy production.Several gene mutations result in deficiency of synthesis of CoQ10.
The age of presenetation is variable. Renal involvement also is variable from isolated nephrotic syndrome, steroid-resistant nephrotic syndrome (with or without encephalomyopathy) to neonatal renal failure.