The theory of the 'mana personality' in Jung's works: a historic-hermeneutic perspective. Part II.

This is the second part of an article that tries to provide a framework of understanding of, and a seminal reflection on, a highly interesting yet little explored psychological construct of Jung's analytical psychology, namely the 'mana personality'. Here I take into consideration some issues around the 'saviour complex', discussed in Jung's seminar on Nietzsche's Zarathustra, concerning both the psychological analysis of the individual and the socio-political level related to the collective horizon of the 1930s. Moreover, I consider the continuity of Jung's analysis of such issues in other works such as 'Psychology and national problems' (1936), Symbols of Transformation (1952), and Aion (1950). I finally make some suggestions concerning Jung's apparent hermeneutic tendency to apply the construct of the mana personality to collective historical phenomena.

Ceci est la deuxième partie d'un article qui cherche à fournir une structure pour la compréhension d'un concept très intéressant et pourtant peu étudié de la psychologie analytique de Jung, à savoir la « personnalité mana ¼, et pour une réflexion fondamentale sur ce concept. Je me penche ici sur des questions concernant le « complexe du sauveur ¼, questions abordées dans le séminaire de Jung sur le Zarathoustra de Nietzsche, et qui concernent à la fois l'analyse psychologique de l'individu et le niveau socio-politique en lien avec l'horizon collectif des années 1930. De plus, je m'intéresse à la continuité de l'analyse de Jung sur ces questions avec d'autres travaux, tels que « Psychologie et problèmes nationaux ¼ (1936), Symboles de la Transformation (1952), et Aïon (1950). Je fais finalement quelques suggestions à propos de la tendance herméneutique manifeste de Jung à appliquer le concept de personnalité mana aux phénomènes historiques collectifs.

Esta es la segunda parte de un artículo que intenta ofrecer un marco de referencia para la compresión de, y una reflexión seminal sobre, un constructo de la psicología analítica de Jung, sumamente interesante y todavía poco explorado, denominado 'personalidad mana'. Aquí tomo en consideración algunos puntos con relación al 'complejo de sabio', desarrollados en el seminario sobre el Zarathustra de Nietzsche, que conciernen tanto al análisis del individuo y al nivel socio-político relativo al horizonte colectivo de 1930. A su vez, considero la continuidad del análisis de Jung sobre dichos temas en otros trabajos como 'Psicología y los problemas nacionales' (1936), Símbolos de Transformación (1952), y Aion (1950). Finalmente, expreso algunas sugerencias con respecto a la tendencia hermenéutica aparente en Jung para aplicar el constructo de la personalidad mana al fenómeno colectivo histórico.

The construct of the 'mana personality' in Jung's works: a historic-hermeneutic perspective. Part I.

According to Jung, the 'mana personality' represents an archetypal phase of the individuation process of remarkable interest in psychological, hermeneutic and theoretical terms. This figure is characterized by a high initiatic potential that fosters the approximation of the consciousness of the Self. At the same time, it entails a risk of psychic inflation or of 'similarity to God'. In this article, divided in two parts, I deal with those aspects through a reconstruction of the development of this notion within Jung's published works, adopting a primarily chronological and, secondarily, thematic approach moving from a textual analysis of relevant passages. In this first part, I consider some passages which deal mainly with the risks of the assimilation of the unconscious in 'La structure de l'inconscient' (1916) that preceded the successive proper treatment of the mana personality's notion presented, and here examined, in 'The relations between the ego and the unconscious' (1928). Successively, I take into consideration some further issues related to it discussed by Jung in 'The structure of the psyche' (1928/1931), 'Archaic man' (1931), and 'Nietzsche's Zarathustra'.

Selon Jung, la « personnalité mana ¼ représente une phase archétypale du processus d'individuation, phase d'un intérêt psychologique, herméneutique et théorique remarquable. Cette figure est caractérisée par un haut potentiel initiatique qui nourrit l'approximation de la conscience du Soi. En même temps, elle comporte le risque d'une inflation psychique, d'une « parenté avec Dieu ¼. Dans cet article, qui est divisé en deux parties, je m'occupe de ces aspects au travers de la reconstruction du développement de cette notion dans les écrits publiés de Jung, adoptant principalement une approche chronologique mais aussi une approche thématique à partir d'une analyse textuelle de passages pertinents. Dans cette première partie, j'examine les passages qui s'occupent surtout des risques d'assimilation de l'inconscient dans « La structure de l'inconscient ¼ (1916) qui a précédé le véritable traitement de la notion de personnalité mana. Celle-ci est ici examinée dans « Dialectique du moi et de l'inconscient ¼ (1928). Je prends ensuite en compte des points qui s'y rapportent et qui sont explorés par Jung dans « La structure de l'âme ¼ (1928/1931), « L'homme archaïque ¼ (1931), et dans «Le Zarathoustra de Nietzsche ¼.

De acuerdo a Jung, la 'personalidad mana' representa una fase arquetipal del proceso de individuación, de un interés remarcable en términos psicológicos, hermenéuticos y teóricos. Esta figura es caracterizada por un alto potencial iniciático que promueve la aproximación de la conciencia del Sí Mismo. Al mismo tiempo, conlleva el riesgo de inflación psíquica o de 'similitud con Dios'. En el presente artículo, dividido en dos partes, trato con dichos aspectos a través de la reconstrucción del desarrollo de esta noción en las obras publicadas de Jung, adoptando un abordaje, inicialmente cronológico y en segunda instancia temático, a través del análisis textual de pasajes relevantes. En esta primera parte, considero algunos pasajes, los cuales dan cuenta de los riesgos de la asimilación del incosnciente en 'La estructura del inconsciente' (1916) que precede el tratamiento sucesivo y correcto de la noción de 'personalidad mana', presentada, y aquí examinada, en 'La relación entre el ego y el inconsciente' (1928). Sucesivamente, tomo en consideración otras cuestiones relacionadas con ésta expresadas por Jung en 'La estructura de la psique' (1928/1931), 'Hombre Arcaico' (1931), y el Zarathustra de Nietzsche.

Expanded Newborn Screening Using Tandem Mass Spectrometry: Seven Years of Experience in Eastern Sicily.

The expanded newborn screening for selected inborn errors of metabolism (IEM) in Sicily was introduced in 2007 by a Regional project entitled "Early detection of congenital metabolic diseases: expanded neonatal screening". It established two newborn screening laboratories, for Western and Eastern Sicily, which started their activity in 2011. Here we present the results of expanded screening (excluding phenylketonuria (PKU)) of the Eastern laboratory from January 2011 to December 2017. Our data highlight the importance of the expanded newborn screening as a basic health program to avoid the underestimation of rare diseases and the need of further investigations even when there are no textbook alterations of the metabolic profiles. We performed our analysis on dried blood spot by tandem mass spectrometry, according to Italian guidelines. A total of 196 samples from 60,408 newborns gave positive screening results (recall rate 0.32%) while 12 babies were true positive, including 2 newborns whose mothers resulted in being affected by a metabolic disease. The overall frequency of IEM found in the screening panel was 1:6041 (mothers excluded) or 1:5034 (mothers included). The introduction of MS/MS technology in Sicily has significantly increased the detection of inherited metabolic disorders, including those not previously covered, with a predictable improved outcome for several disorders.

Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome.

Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu261 , Leu262 , and Arg265 in 16 unrelated individuals with clinical diagnosis of NS or with features suggestive for this disorder, specifying a novel disease-causing mutation cluster. Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling. Structural data predicted a gain-of-function role of substitutions at residues Leu262 and Arg265 exerted by disruption of the N-SH2/PTP autoinhibitory interaction. Molecular dynamics simulations suggested a more complex behavior for changes affecting Leu261 , with possible impact on SHP2's catalytic activity/selectivity and proper interaction of the PTP domain with the regulatory SH2 domains. Consistent with that, biochemical data indicated that substitutions at codons 262 and 265 increased the catalytic activity of the phosphatase, while those affecting codon 261 were only moderately activating but impacted substrate specificity. Remarkably, these mutations underlie a relatively mild form of NS characterized by low prevalence of cardiac defects, short stature, and cognitive and behavioral issues, as well as less evident typical facial features.

Mutation spectrum of NF1 gene in Italian patients with neurofibromatosis type 1 using Ion Torrent PGM™ platform.

Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more café au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve sheath tumours and plexiform neurofibromas. Mutation detection is complex, due to the large gene size, the large variety of mutations and the presence of pseudogenes. Using Ion Torrent PGM™ Platform, 73 mutations were identified in 79 NF1 Italian patients, 51% of which turned out to be novel mutations. Pathogenic status of each variant was classified using "American College of Medical Genetics and Genomics" guidelines criteria, thus enabling the classification of 96% of the variants identified as being pathogenic. The use of Next Generation Sequencing has proven to be effective as for costs, and time for analysis, and it allowed us to identify a patient with NF1 mosaicism. Furthermore, we designed a new approach aimed to quantify the mosaicism percentage using electropherogram of capillary electrophoresis performed on Sanger method.

Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients.

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.

Hyperprolinemia Type IA: Benign Metabolic Anomaly or a Trigger for Brain Dysfunction?

Abstract Objective: Hyperprolinemia type I (HPI) is a rare and inherited autosomal recessive disorder caused by proline oxidase deficiency. Hyperprolinemia type 1 is biochemically defined as high plasma proline levels without urinary ?-1-pyrroline-5-carboxylate excretion. Hyperprolinemia type 1 has been considered a benign metabolic disorder, but a relationship with neurological disorders has recently been suggested. Study Design: We retrospectively analyzed plasma amino acid values obtained by amino acid analysis from 10 030 children admitted for neurological reasons during the years 1996 to 2010 at the Regional Sicilian Centre for Metabolic Diseases. Patients with proline levels above the normal range of 129 to 245 ?M were identified. Results: Only 2 children showed high levels of proline (450-480 ?M and 380-470 ?M, respectively), but their disorders (tubercular neuroencephalitis and progressive mitochondrial encephalopathy) did not seem to be related to hyperprolinemia as a causative factor. Conclusion: The question of HPI as benign metabolic anomaly or as a direct cause of brain damage is still open. Since HPI is rare, other observations on this regard are necessary.

Quantitative analysis of upright standing in adults with late-onset Pompe disease.

Pompe disease is a rare disorder producing muscle weakness and progressive impairments in performing daily motor activities, such as walking and standing. Most studies have focused on dysfunctions at cellular level, restricting the examination of gross motor functions to qualitative or subjective rating scales evaluations. With the aim of providing an instrumented quantification of upright standing in Pompe disease, we used a force platform to measure the center of pressure over three foot positions and with eyes open and closed. Amplitude and variability of body sway were measured to determine the level of postural stability, while power spectrum analysis and nonlinear computations were performed to explore the structure of the postural control. In comparison with healthy participants, patients with Pompe disease showed a reduced level of postural stability, but irrelevant variations in frequency content and spatio-temporal structure of the sway motion were detected. Changes in foot position did not increase the postural instability associated with Pompe disease, but prominent worsening occurred in the patients when they stand with eyes closed, particularly along the anterior-posterior direction. These results provide objective elements to monitor deficiencies of upright standing in Pompe disease, emphasizing the specific contributions of sway direction and sensory deficits.

A multi-method approach to the molecular diagnosis of overt and borderline 11p15.5 defects underlying Silver-Russell and Beckwith-Wiedemann syndromes.

BACKGROUND: Multiple (epi)genetic defects affecting the expression of the imprinted genes within the 11p15.5 chromosomal region underlie Silver-Russell (SRS) and Beckwith-Wiedemann (BWS) syndromes. The molecular diagnosis of these opposite growth disorders requires a multi-approach flowchart to disclose known primary and secondary (epi)genetic alterations; however, up to 20 and 30 % of clinically diagnosed BWS and SRS cases remain without molecular diagnosis. The complex structure of the 11p15 region with variable CpG methylation and low-rate mosaicism may account for missed diagnoses. Here, we demonstrate the relevance of complementary techniques for the assessment of different CpGs and the importance of testing multiple tissues to increase the SRS and BWS detection rate. RESULTS: Molecular testing of 147 and 450 clinically diagnosed SRS and BWS cases provided diagnosis in 34 SRS and 185 BWS patients, with 9 SRS and 21 BWS cases remaining undiagnosed and herein referred to as "borderline." A flowchart including complementary techniques and, when applicable, the analysis of buccal swabs, allowed confirmation of the molecular diagnosis in all borderline cases. Comparison of methylation levels by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in borderline and control cases defined an interval of H19/IGF2:IG-DMR loss of methylation that was distinct between "easy to diagnose" and "borderline" cases, which were characterized by values ≤mean -3 standard deviations (SDs) compared to controls. Values ≥mean +1 SD at H19/IGF2: IG-DMR were assigned to borderline hypermethylated BWS cases and those ≤mean -2 SD at KCNQ1OT1: TSS-DMR to hypomethylated BWS cases; these were supported by quantitative pyrosequencing or Southern blot analysis. Six BWS cases suspected to carry mosaic paternal uniparental disomy of chromosome 11 were confirmed by SNP array, which detected mosaicism till 10 %. Regarding the clinical presentation, borderline SRS were representative of the syndromic phenotype, with exception of one patient, whereas BWS cases showed low frequency of the most common features except hemihyperplasia. CONCLUSIONS: A conclusive molecular diagnosis was reached in borderline methylation cases, increasing the detection rate by 6 % for SRS and 5 % for BWS cases. The introduction of complementary techniques and additional tissue analyses into routine diagnostic work-up should facilitate the identification of cases undiagnosed because of mosaicism, a distinctive feature of epigenetic disorders.

Prevalence of anti-adeno-associated virus serotype 8 neutralizing antibodies and arylsulfatase B cross-reactive immunologic material in mucopolysaccharidosis VI patient candidates for a gene therapy trial.

Recombinant vectors based on adeno-associated virus serotype 8 (AAV8) have been successfully used in the clinic and hold great promise for liver-directed gene therapy. Preexisting immunity against AAV8 or the development of antibodies against the therapeutic transgene product might negatively affect the outcomes of gene therapy. In the prospect of an AAV8-mediated, liver-directed gene therapy clinical trial for mucopolysaccharidosis VI (MPS VI), a lysosomal storage disorder caused by arylsulfatase B (ARSB) deficiency, we investigated in a multiethnic cohort of MPS VI patients the prevalence of neutralizing antibodies (Nab) to AAV8 and the presence of ARSB cross-reactive immunologic material (CRIM), which will either affect the efficacy of gene transfer or the duration of phenotypic correction. Thirty-six MPS VI subjects included in the study harbored 45 (62.5%) missense, 13 (18%) nonsense, 9 (12.5%) frameshift (2 insertions and 7 deletions), and 5 (7%) splicing ARSB mutations. The detection of ARSB protein in 24 patients out of 34 (71%) was predicted by the type of mutations. Preexisting Nab to AAV8 were undetectable in 19/33 (58%) analyzed patients. Twelve out of 31 patients (39%) tested were both negative for Nab to AAV8 and CRIM-positive. In conclusion, this study allows estimating the number of MPS VI patients eligible for a gene therapy trial by intravenous injections of AAV8.

Erythema Nodosum and Mycoplasma pneumoniae Infections in Childhood: Further Observations in Two Patients and a Literature Review.

Erythema nodosum (EN) is the most frequent panniculitis in childhood and has been associated with various conditions, such as infectious and autoimmune disorders, medications, and malignancies. The author reports on two children affected with EN associated with Mycoplasma pneumoniae infection, which occurred in one patient without pulmonary detection. The available literature on EN and M. pneumoniae infection in childhood is also reviewed.

Familial 1q22 microduplication associated with psychiatric disorders, intellectual disability and late-onset autoimmune inflammatory response.

BACKGROUND: Despite the extensive use of chromosomal microarray technologies in patients with neurodevelopmental disorders has permitted the identification of an increasing number of causative submicroscopic rearrangements throughout the genome, constitutional duplications involving chromosome 1q22 have seldom been described in those patients. RESULTS: We report on a pedigree with seven affected members showing varying degrees of behavioural and emotional disturbances including general anxiety disorder, mood disorders, and intellectual disability. Two adult female patients also showed late onset autoimmune inflammatory responses characterized by alopecia, skin ulcers secondary to inflammatory vasculitis, interstitial lung disease, and Raynaud's phenomenon. Array-CGH analysis identified in the affected individuals a 290 Kb microduplication in the chromosome 1q22. The rearrangement involves eleven known genes and is not present in the databases of polymorphic copy number variants. CONCLUSIONS: The rearrangement segregates with the neurological clinical features observed in our patients, suggesting that dosage imbalance of one or more genes in this genomic region may lead to the observed phenotype. The association between the microduplication and the inflammatory disease is much less evident. Additional reported patients carrying similar microduplications are needed to clarify this aspect.

CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases.

Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously-unreported mutations in ZEB2. Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present.

Nonconvulsive status epilepticus complicating epstein-barr virus encephalitis in a child.

Children with acute encephalopathy show prolonged electrographic seizure activity consistent with nonconvulsive status epilepticus (NCSE). Pediatric NCSE is a heterogeneous clinical entity with poor outcome and different etiologies, including central nervous system infection, stroke, toxic-metabolic syndrome, and epileptic syndrome. We report a 4-year-old girl with seizure and behavioral changes in whom the analysis of cerebrospinal fluid by polymerase chain reaction was positive for Epstein-Barr virus. We emphasize the importance of electroencephalography (EEG), and particularly, of continuous EEG monitoring for early recognition and appropriate treatment of this condition.

Imaging findings of mucopolysaccharidoses: a pictorial review.

INTRODUCTION: Mucopolysaccharidosis (MPS) represent a heterogeneous group of inheritable lysosomal storage diseases in which the accumulation of undegraded glycosaminoglycans (GAGs) leads to progressive damage of affected tissues. The typical symptoms include organomegaly, dysostosis multiplex, mental retardation and developmental delay. Definitive diagnosis is usually possible through enzymatic assays of the defective enzyme in cultured fibroblasts or leukocytes. IMAGING FINDINGS: Radiological and neuroradiological findings are reported. The most important neuroradiological features include abnormal signal intensity in the white matter, dilatation of periventricular spaces, widening of cortical sulci, brain atrophy, enlargement of extraventricular spaces and spinal cord compression. With reference to the skeletal system, most important radiological findings include multiplex dysostosis, which is represented by several bone malformations found in the skull, hands, legs, arms and column. The abnormal storage of GAGs leads to liver and spleen enlargement; it also damages cartilage layers and synovial recesses in the joints. CONCLUSION: The aim of this pictorial essay is to describe the imaging findings of MPS, represented by skeletal and neurological features; skeletal X-ray and MR allow an assessment of the severity of disease, to plan medical and surgical therapy and to evaluate response to treatment. TEACHING POINTS: • To describe the imaging findings common to different types of MPS. • To describe multiplex dysostosis encountered in the axial and appendicular skeleton. • To evaluate neuroradiological features of MPS, including brain abnormal signal intensity and atrophy. • To evaluate important otorhinolaryngological problems, such as otitis media and airways obstruction.

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.

Auditory system involvement in late onset Pompe disease: a study of 20 Italian patients.

Glycogen storage disease type II (GSD II), also known as Pompe disease, is an autosomal recessive inherited disorder caused by a reduced activity of acid alpha glucosidase (GAA). Two different clinical entities have been described: rapidly fatal infantile and late onset forms. Hearing loss has been described in classic infantile Pompe patients but rarely in late onset cases. The main purpose of this study was to investigate the involvement of the auditory system in a cohort of Italian patients with late onset GSD II. We have enrolled 20 patients, 12 males and 8 females. The auditory system assessment included speech and pure tone audiometry, impedance audiometry and auditory brainstem responses (ABR). A combined interpretation of those tests allowed us to define the origin of the hearing impairment (sensorineural, conductive or mixed). Clinically, all patients but one denied subjective hearing disturbances. On the other hand, audiological evaluation revealed that 21/40 patient ears (52.5%) had a hearing impairment: 57% had a sensorineural deficit, 33% showed a conductive hearing loss whereas 10% presented with a mixed pattern. Our study revealed that, in this group of GSDII late onset patients, the auditory system impairment was more frequently present than thought with a prominent cochlear involvement. Our results emphasize the importance of a routinely auditory function evaluation in all forms of Pompe disease.