Psychiatric burden in a cohort of adults with Niemann Pick type C disease: from psychotic symptoms to frontal lobe behavioral disorders.

OBJECTIVES: To describe Niemann-Pick type C (NP-C) behavioral symptoms (focusing on psychotic symptoms) and its relation to frontal lobe functioning. METHODS: We retrospectively reviewed medical charts of NP-C-patients followed in the Lysosomal Diseases reference center in Paris Pitié-Salpêtrière. We collected demographic data, psychiatric clinical manifestations, psychometric scales, and extended neuropsychological data including executive and behavioral frontal lobe functions evaluations. RESULTS: Nineteen patients were included in the study with ten of them having experienced at least one acute psychotic episode, being inaugural for six of them. Most of the patients suffered from behavioral (15/17) and cognitive disorders (18/19) (including executive dysfunction (11/12), apathy (13/17), impaired social cognition (11/13) and stereotyped behaviors (5/10). For five patients, quality of life was significantly impaired by these abnormal behaviors. Concerning frontal neuropsychological evaluation, Facial emotion recognition was by far the most performed neuropsychological test (n = 8) and the score was always abnormal. It is noteworthy that psychotic symptoms were often drug resistant (8/9) and that Miglustat was associated with a better control of psychotic symptoms. CONCLUSIONS: We report a high frequency of psychiatric symptoms in NP-C encompassing acute psychotic manifestations, often presenting early in the course of the disease with atypical features. We also report disabling behavioral manifestations related to frontal dysfunction.

Sensory neuronopathy as a major clinical feature of mitochondrial trifunctional protein deficiency in adults.

INTRODUCTION: Mitochondrial trifunctional protein deficiency (MTPD) is a long-chain fatty acid oxidation disorder characterized by co-existence of rhabdomyolysis episodes and peripheral neuropathy. Two phenotypes are described: generalized mitochondrial trifunctional protein deficiency (gMTPD) and isolated long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency (iLCHADD) that is always associated with the c.1528G>C mutation. Peripheral neuropathy of MTPD is commonly described in children as axonal, length-dependent and sensorimotor. OBJECTIVES: To report clinical and electrophysiological features of four independent adult MTPD patients with peripheral neuropathy. RESULTS: Onset of the disease was characterized in all patients by rhabdomyolysis episodes occurring during childhood preceded by severe hypoglycemic episodes in three patients. Peripheral nerve involvement manifesting as sensory ataxia appeared later, during adolescence or adulthood. In all cases, electroneuromyogram showed no length-dependent sensory potentials decrease characteristic of sensory neuronopathy ("ganglionopathy"). All patients harbored at least one c.1528G>C mutation. DISCUSSION: We describe MTPD as a newly hereditary etiology of sensory neuronopathy in adults, specifically in patients with c.1528G>C mutation. MTPD should be screened for by performing plasma acylcarnitines in patients with chronic sensory neuronopathy and additional suggestive features such as exercise intolerance or retinopathy.

Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: An MRI Study of 16 French Cases.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is an autosomal dominant leukoencephalopathy related to CSF1R gene mutations. A growing number of clinicoradiologic phenotypes have been described. In this study, we analyzed brain imaging findings in 16 patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia to refine radiologic diagnostic clues. T2/FLAIR white matter hyperintensities were present in all patients with frontal or frontoparietal predilection, with asymmetric distribution in more than one-third. Brain atrophy and callosal involvement were almost constant, and corticospinal tract involvement was frequent. Moreover, deep white matter hyperintense dots on DWI and deep punctate calcifications on CT were often found. Conversely, deep gray matter nuclei, external capsules, and brain stem were rarely involved. Our series emphasized the great variability of MR imaging findings seen in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. A complete imaging screening including DWI, T2*, and CT is mandatory to accurately assess patients with suspected inherited adult-onset leukoencephalopathy.