Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect.

Creatine transporter deficit (CT1) is an inherited metabolic disorder that causes mental retardation, epilepsy, speech, language and behavioral deficits. Until now, no treatment has been proven to be successful for this condition. We describe 1-year follow-up study of a child, aged 9.6 years, with CT1 defect, on oral supplementation with L-arginine, a precursor of creatine synthesis. Under supplementation, he showed a noticeable improvement of neurological, language and behavioral status and an increase of brain creatine and phosphocreatine documented with magnetic resonance spectroscopy. The results suggest that children with CT1 disorder show some residual adaptive plasticity for certain functions even at quite an advanced age. Further trials with higher L-arginine dosages and more protracted treatment are encouraged.

Mental retardation and verbal dyspraxia in a new patient with de novo creatine transporter (SLC6A8) mutation.

We report on a 9.5-year-old Italian boy affected by creatine transporter deficit (CT1), due to a de novo mutation in SLC6A8 gene. The patient was investigated by means of a comprehensive neuropsychological protocol and presented with an unusual alteration of speech and expressive-language function, associated with mental retardation, that differed from CT1 patients described to date. In particular, he exhibited a developmental apraxia of speech (DAS) with motor planning and execution deficit, while receptive language was consistent with his mental age.

Proton MR spectroscopy of mitochondrial diseases: analysis of brain metabolic abnormalities and their possible diagnostic relevance.

BACKGROUND AND PURPOSE: Proton (hydrogen-1 [(1)H]) MR spectroscopy is a useful diagnostic tool in many metabolic diseases, but only scattered and inconclusive data are available on mitochondrial diseases. We performed MR imaging and (1)H MR spectroscopy of the brain in patients with different types of primary mitochondrial diseases to investigate the role of (1)H MR spectroscopy in the clinical evaluation of these disorders. METHODS: In 15 patients (11 adults, four children) with mitochondrial diseases, localized MR spectra were obtained at short TEs in cerebellar white matter, paratrigonal white matter, and parieto-occipital cortex that appeared normal on MR images. Additional spectra of basal ganglia and cortical gray matter structural lesions were obtained in three patients. RESULTS: A significant choline reduction and N-acetylaspartate reduction were found in areas that appeared normal on MR images. Lactate was never found in areas that appeared normal on MR images, except in two children in whom MR studies were performed during episodes of symptom exacerbation and revealed elevated lactate both in areas that appeared damaged on MR images and in normal-appearing areas. An additional abnormal signal at 0.9 ppm was found in a consistent number of studies. CONCLUSION: (1)H MR spectroscopy proved to be a useful investigational tool for mitochondrial diseases, as it enabled detection of metabolic abnormalities even in areas of brain that appeared normal on MR images, especially when it was performed during episodes of clinical relapses or clinical exacerbation.

Unusual clinical and magnetic resonance imaging findings in a family with proteolipid protein gene mutation.

BACKGROUND: Pelizaeus-Merzbacher disease (PMD) and a complicated form of familial spastic paraparesis (spastic paraplegia 2 [SPG2]) are X-linked development disorders of myelin formation caused by a mutation in the proteolipid protein (PLP) gene. Spastic paraplegia 2 is allelic to PMD. The wide range of PLP mutations results in a corresponding large spectrum of clinical severity in PMD, with a continuum of signs and symptoms to SPG2. OBJECTIVE: To report the results of genetic, neurophysiologic, and neuroimaging investigations performed in a child affected by a mild ataxic and spastic form of PLP-related disorder and in his relatives. RESULTS: A missense mutation in exon 6 of the PLP gene (Q233P) was found in the proband and in the female obligate carriers. In the proband, evoked potentials were altered and remained unchanged during the 7 years of follow-up. Magnetic resonance imaging of the child demonstrated patchy hyperintensities of the paraventricular white matter, with microcystic components. These latter findings, along with pallidal calcium deposition, were also present in 2 females heterozygous for PLP mutation. CONCLUSION: The unusual genetic, magnetic resonance imaging, and clinical findings of this family confirm the wide variability of PLP-related disorders.

Leukoencephalopathy with bilateral anterior temporal lobe cysts: a further case of this new entity.

The introduction of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy into clinical practice has permitted advances in the definition and categorization of unknown leukodystrophies in children. We report a new type of leukodystrophy, defined by particular MRI and clinical findings, in a child with uneventful pre- and perinatal histories, spasticity, severe mental impairment with absence of language, and deafness. Brain MRI showed lobar white-matter signal abnormalities with extensive cysts in the anterior temporal lobe. The results of all metabolic screening tests, including the specific investigations for leukodystrophy, have been negative. Six years of clinical and MRI-magnetic resonance spectroscopy patient follow-up indicate a nonprogressive clinical and magnetic resonance picture. Owing to the striking similarities with the previous eight patients reported, this additional case supports the identification of a new leukodystrophy.