Maple syrup disease presenting as paroxysmal dystonia

Abstract

An apparently normal 22-month-old boy was evaluated because of weekly paroxysmal episodes consisting of curvature of the body (alternating sides). During attacks, which lasted 5 minutes to 8 hours, the patient had extreme irritability. We hypothesized based on the clinical picture that the paroxysmal events might correspond to partial epileptic seizures, hemiplegic migraine, paroxysmal torticollis, or Sandifer’s syndrome. Blood count, hepatic and renal function, ionogram, and glycemia were normal. Electroencephalogram showed left temporal slow waves. Brain computed tomography scan was normal. The patient was put on sodium valproate (30mg/kg/ day PO). Two months later, the patient had similar weekly attacks. These episodes were videotaped, and we were able to diagnose a paroxysmal dystonia accompanied by irritability. Physical and neurological examination was normal between the attacks. Mental age showed a delay of 10 months of global development (Griffiths scale). Brain magnetic resonance imaging (MRI) showed symmetrical hypersignal in T2-weighted images in the brainstem, globus pallidus, thalami, and dentate nuclei (see Fig). Serum and urinary amino acid analysis in the interictal periods disclosed abnormally high leucine (489 mol/L; normal, 109), isoleucine (278 mol/L; normal, 94), valine (500 mol/L; normal, 246), and alloisoleucine (88 mol/L; normal, 3.4) levels. Urinary organic acid chromatography was normal. Serum leucine level was 300 mol/L after 5 days’ treatment with a vegetarian diet and milk substitute. Supplementation with high doses of thiamine did not improve the metabolic picture. Ten months after maple syrup urine disease (MSUD) was diagnosed, the patient had only two mild attacks of dystonia accompanied by metabolic decompensation episodes precipitated by fever. In addition, his psychomotor development improved, particularly verbal capacities. Brain MRI has not shown significant differences, however. Most episodes of paroxysmal dyskinesia in children are idiopathic. Secondary metabolic causes include nonketotic hyperglycinemia, hypoglycemia, hypocalcemia, thyrotoxicosis, kernicterus, cystinuria, and pyruvate carboxylase deficiency. We have presented a patient with episodes of nonkinesigenic paroxysmal dystonia accompanied by marked irritability. This makes this case different from typical idiopathic dystonias. Left temporal electroencephalogram abnormalities suggested a diagnosis of epilepsy, but it was quite improbable given the alternating location of the dystonic attacks and the failure to respond to antiepileptic therapy. Brain MRI pointed to a symptomatic cause (metabolic, toxic, or anoxic). The abnormal levels of branched-chain amino acids in the interictal periods with persistently high alloisoleucine levels have helped us diagnose chronic intermediate MSDU. Nonspecific developmental delay, progressive psychomotor retardation, dementia, and seizures can be observed during the course of this disease. Although age at onset, delayed psychomotor development, and typical brain imaging make this case similar to others, our patient atypically presented with paroxysmal dystonia. MSUD should be considered in the differential diagnosis of secondary causes of childhoodonset paroxysmal dyskinesia.