A two year old girl with copper deficiency progressive neuronal disorder and granulocytopenia is reported from the Department of Pediatrics, Kyoto University, Japan. A familial granulocytopenia was noted at one month of age and she developed truncal ataxia and progressive neurologic regression at age two years, shortly after a ten day fever. She was admitted with a diagnosis of acute cerebellar ataxia and later developed dysarthria, mild dysphagia and was then unable to speak two word sentences. She was referred to the Utano National Hospital, Kyoto, three months after the onset. She was well nourished, her hair was normal, and she had no hepatosplenomegaly. Truncal and limb ataxia, horizontal nystagmus, increased reflexes and extensor plantar reflexes were noted. CT showed cerebellar atrophy and symmetric low-density areas in the bilateral periventricular white matter. Sural nerve biopsy revealed axonal degeneration. Blood lactate levels were high (25.8/mg/dl) and serum levels of copper and ceruloplasmin and urinary excretion of copper were low. Cultured skin fibroblasts showed normal copper uptake. Copper given orally 0.1 mg/kg daily for three days resulted in increased serum copper and ceruloplasmin levels, normal granulocyte count, hemoglobin level, blood lactate and pyruvate levels, but neither clinical improvement nor normalization of copper, lactate and pyruvate levels in the CSF were noted. The patient deteriorated slowly, the MRI showed extension of high signal T2-weighted images and newly appearing lesions in the basal ganglia. At age three years (11 months after onset) she had spastic tetraplegia with respiratory difficulty and was placed on a respirator. [1]

COMMENT. The clinical and MRI features of this patient ruled out the diagnosis of Wilson’s disease, and Menkes’ disease was unlikely in the absence of pili torti and with a normal copper uptake in cultured fibroblasts. The authors speculated that copper transport across the intestinal wall and across the blood brain barrier was impaired in their patient, and that long-term copper deficiency in the brain might have caused irreversible damage to cytochrome c oxidase production. (Dr. Fujii is presently at The Burke Rehab Ctr., White Plains, NY).