Intellectual Disability, Falls and Gait Disturbances: A Misd
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This report describes the case of a 27-year-old man presenting with slowly progressive extrapyramidal dysfunction and learning disability considered to have a syndromic intellectual disability. The re-evaluation of the clinical features and the investigations performed led to the diagnosis of atypical pantothenate kinase-associated neurodegeneration (PKAN).

The patient was a 27-year-old man presenting with gait disturbance and falls. Some episodes of unmotivated laughing, and problems keeping up in school and needing support, were also referred to. There was no tremor, bradykinesia or other symptoms. Past medical history was relevant for an episode of moderate hypoglycemia 2 hours after birth and normal psychomotor development until he was 5 years of age when his mother remarked that the patient sometimes had difficulties in terms of remaining straight in a chair, handling objects and falls. Difficulty with self-help and self-care skills was also noted. In addition, gait problems started at age 8 when he was seen by an orthopedic specialist without any diagnosis. He was evaluated by a psychiatrist who considered the patient to present a syndromic intellectual disability. The family history was irrelevant.

The physical examination revealed an intellectual coefficiency border-line. Cranial nerves, muscle strength, muscle tone, and osteotendinous reflexes were normal. The finger-to-nose test was normal. No bradykinesia or tremor was noted. However, a slight troncular stiffness and dystonic posture of the left foot were found. The cardiorespiratory and abdominal examinations were unremarkable.

Laboratory investigations showed a normal complete blood count, normal electrolytes and normal renal function. The liver, coagulation, and thyroid function test results were within the normal range. The chemistry panel was completed by the determination of ferritin, copper, ceruloplasmin, serum phenylalanine and long-chain fatty acids, without any abnormal results. In this setting, a karyotype study was performed which excluded fragile X syndrome. Magnetic resonance imaging (MRI) showed bilateral, symmetric foci of T2 hyperintensity in the globus pallidus (GP) surrounded by pallidal T2 hypointensity, the so-called “Eye-of-the-tiger” sign. A genetic panel for NBIA, specifically PKAN, was ordered for this patient, including pantothenate kinase 2 (PANK2) testing – the genetic marker for pantothenate kinase 2 (PanK2) enzyme. This showed a PANK2 gene mutation.

Learning points:
1. Patients with an intellectual disability should be carefully evaluated.

2. In the evaluation of a patient with extrapyramidal dysfunction for several years, with gradual progression, spasticity, and psychiatric disturbances, PKAN should be considered.