Child Neurology: Two sisters with dystonia and regression: PLA2G6-associated neurodegeneration.

CLINICAL CASE, PART 1 A 19-month-old girl presented for neurologic consultation for delayed walking. She rolled at 6 months, sat unsupported at 8 months, but never walked independently. She babbled only. Her examination was notable for slightly decreased bulk in her legs, mild truncal hypotonia, and decreased deep tendon reflexes. She had difficulty pulling to stand and could only walk with support. She exhibited a steppage gait with hyperextension of her knees, exaggerated lifting of her feet, and out-turning of her ankles. Birth history was unremarkable and parents were not consanguineous. A head CT performed at 13 months for mild head trauma was normal. The initial diagnostic workup was directed at causes of gait abnormality and developmental delay. Initial metabolic screening labs, including serum lactate/pyruvate, amino acids, creatine phosphokinase, carnitine, lipid panel, and coenzyme Q10 profile, were normal. MRI of the spine was normal. At age 23 months, brain MRI showed new mild to moderate cerebellar atrophy and minimal brainstem volume loss (figure). By age 26 months, the patient developed pain and dystonia in her legs. On examination, she had striatal toes (spontaneous extensor plantar response without fanning of the toes) and continued decreased deep tendon reflexes. She could no longer stand, although she still crawled. Repeat brain MRI at 29 months showed progressive cerebellar volume loss. By age 31 months, she developed a mild spastic quadriparesis and continued to have significant painful dystonic posturing of lower extremities. Developmental regression continued. She was no longer able to sit independently or crawl and only made occasional sounds. She developed bilateral optic atrophy and intermittent left esotropia.