Maria Cristina Bianchi

Arginine:Glycine Amidinotransferase Deficiency: The Third Inborn Error of Creatine Metabolism in Humans

Arginine:glycine amidinotransferase (AGAT) catalyzes the first step of creatine synthesis, resulting in the formation of guanidinoacetate, which is a substrate for creatine formation. In two female siblings with mental retardation who had brain creatine deficiency that was reversible by means of oral creatine supplementation and had low urinary guanidinoacetate concentrations, AGAT deficiency was identified as a new genetic defect in creatine metabolism. A homozygous G-A transition at nucleotide position 9297, converting a tryptophan codon (TGG) to a stop codon (TAG) at residue 149 (T149X), resulted in undetectable cDNA, as investigated by reverse-transcription PCR, as well as in undetectable AGAT activity, as investigated radiochemically in cultivated skin fibroblasts and in virus-transformed lymphoblasts of the patients. The parents were heterozygous for the mutant allele, with intermediate residual AGAT activities. Recognition and treatment with oral creatine supplements may prevent neurological sequelae in affected patients.

Age dependence of cerebral perfusion assessed by magnetic resonance continuous arterial spin labeling.

To study the normal dependence of cerebral perfusion changes on age, to measure values of perfusion early in life, and to create a reference dataset.

Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree

Arginine:glycine amidinotransferase (AGAT, EC 2.1.4.1) deficiency is a recently recognized autosomal recessive inborn error of creatine biosynthesis, characterized by mental retardation and severe language impairment. We extensively investigated a third 5-year-old patient with AGAT deficiency, discovered in the pedigree of the same Italian family as the two index cases. At the age of 2 years he presented with psychomotor and language delay, and autistic-like behavior. Brain MRI was normal, but brain 1H-MRS disclosed brain creatine depletion, which almost completely normalized following creatine monohydrate supplementation. A remarkable clinical improvement paralleled the restoration of brain creatine concentration. AGAT and GAMT (guanidinoacetate:methyltransferase) genes were analyzed in the proband and in 26 relatives, including the two cousins with AGAT deficiency. Sequencing of the probands AGAT gene disclosed the same homozygous mutation at nt position 9093 converting a tryptophan (TGG) to a stop codon (TAG) at residue 149 (W149X), as already described in the two previously reported cases. The probands parents and 10 additional subjects of the pedigree were carriers for this mutation. AGAT deficiency was further confirmed by undetectable AGAT activity in the patients lymphoblasts. Mutation analysis of the GAMT gene revealed a sequence variation in exon 6 (T209M), not in the proband, but in 15 additional subjects from the pedigree. The silent nature of this sequence variation is supported by its homozygosity in one AGAT deficient cousin and in one asymptomatic adult, both with normal GAMT activity.

Comorbidity with axis I anxiety disorders in remitted psychotic patients 1 year after hospitalization

INTRODUCTION Comorbid anxiety disorders are frequently encountered in psychoses and mainly assessed during the hospitalization. METHODS Comorbidity was investigated in 98 patients with schizophrenia, schizoaffective, or bipolar disorder, previously hospitalized for psychotic symptoms. Assessments, including Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Brief Psychiatric Rating Scale, and Clinical Global Impressions Scale, were performed during hospitalization (t0) and subsequently in a phase of remission (t1). Comorbidity was assessed at t1 only. RESULTS One or more comorbid anxiety diagnoses were made in 46 (46.9%) patients. Of these, 15 (32.6%) received multiple anxiety diagnoses, while 31 (67.4%) single anxiety diagnoses. Schizophrenic patients had a rate of social anxiety disorder (SAD) higher (P<.05) than the others. Patients assessed with panic disorder or with obsessive-compulsive disorder at t1 showed significantly greater severity of illness at t0; patients with SAD demonstrated greater severity at t1. No significant differences in the rates of individual anxiety disorders were found in patients treated with typical or atypical antipsychotics or with both. CONCLUSION Anxiety disorders, particularly obsessive-compulsive disorder, panic disorder and SAD, seem to be frequently comorbid in remitted psychotic patients; SAD would be more prevalent in schizophrenia and might negatively impact the course of the illness.

Influences of Dopaminergic Treatment on Motor Cortex in Parkinson Disease : A MRI/MRS Study

The objective of this study was to investigate neurochemical and metabolic changes in the motor cortex in a group of de novo Parkinsons disease (PD) patients before and after 6 mo treatment with the dopamine agonist pergolide. Proton magnetic resonance spectroscopy (1H‐MRS) has been used to study striatal and cortical metabolism in PD and other parkinsonisms. So far, no studies evaluating possible brain metabolic changes in PD patients before and after dopaminergic therapy have been reported. De novo PD patients (11) and controls (11) underwent clinical evaluation (UPDRS‐III motor evaluation) and a first single‐voxel 1H‐MRS of the motor cortex. 1H‐MRS studies were performed using the PROBE‐SV System implemented on a 1.5 Tesla Scanner (GE Medical System, Milwaukee, WI). Pergolide was administered up to a dose of 1 mg t.i.d. After 6 mo follow‐up, all patients were clinically evaluated and a second single‐voxel 1H‐MRS was performed. Lower values of Cho/Cr and NAA/Cr ratios were observed in the motor cortex of PD patients compared with controls (P < 0.02 and P < 0.01, respectively). After 6 mo therapy with pergolide (1 mg t.i.d), PD patients showed an improvement in motor performances (P < 0.05) and an increase in Cho/Cr ratios in the motor cortex at the second 1H‐MRS evaluation (P < 0.05) was reported. In conclusion, cortical NAA/Cr and Cho/Cr ratios may be impaired in de novo PD. Dopaminergic therapy capable of improving motor function may restore the Cho/Cr ratio in the motor cortex.

Primary intra-diploic meningioma in a child

BackgroundPrimary intra-diploic meningiomas are uncommon in childhood and, at the clinical onset, may be confused with other and more frequent bone tumours because they lack specific clinical and radiological characteristics. Surgery is indicated not only to remove the lesion but also to obtain an accurate histological diagnosis.Case reportWe report the case of a young girl who presented with a recently developed subcutaneous hard mass in the left pterional region. Neuroradiological investigations revealed an intra-osseous lytic mass with a sclerotic reaction. Diagnosis was possible only after the total removal of the tumour and its histological examination.