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Background: Autism Spectrum Disorders (ASDs) are a group of prevalent neuropsychiatric disorders. They present a complex and unknown etiology, which in most cases includes significant peripheral alterations outside the brain such as in the composition of gut microbiota. Because the gut microbiota is involved in modulating the gut-brain axis, several studies have suggested that the microbiome in the gut can modify metabolites which are able to cross the blood-brain barrier and modulate brain function., Methods: We reviewed the current evidence regarding microbiota alterations in patients with ASD and the effects of the administration of probiotics and prebiotics in these patients, both in terms of gastrointestinal and behavioural symptoms., Results: Administration of a probiotic formulation containing different strains of Lactobacillus (L. acidophilus, L. rhamnosus, and others) and Bifidobacteria had beneficial effects upon these aforementioned symptoms and their use is recommended in a subgroup of ASD patients that present gastrointestinal disturbances. Nonetheless, the types of gastrointestinal disturbances that most benefit from such interventions remain to be elucidated in order to personalize the medical approaches., Conclusion: Recent clinical studies have shown that probiotic treatments can regulate the gut microbiota and may result in improvements in some behavioral abnormalities associated with ASD. Trials using prebiotic fibers or synbiotics preparations are still lacking and necessary in order to deep in such therapeutic strategies in ASD with comorbid gastrointestinal disrturbances., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase. In addition to the severe infantile form with cardiac involvement, late-onset variants can affect older children, adolescents (aged >1 year old) or adults. Patients with juvenile (a subgroup of late-onset type) Pompe disease typically do not have cardiac alterations e.g. hypertrophic cardiomyopathy, and the diagnosis is often difficult because it can clinically resemble myriad other neuromuscular disorders. A high level of clinical suspicion is necessary for a timely and accurate diagnosis. We describe 3 interesting cases of patients with juvenile-onset Pompe disease who presented some uncommon clinical features e.g. skeletal alterations and developmental delay, and describe a new genetic variant. Juvenile-onset Pompe disease may be accompanied by uncommon clinical signs that could delay the diagnosis of Pompe disease due to the global pictures resembling other metabolic disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000-3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons-Leu844, Cys845, Ala846, Leu847, and Gly848-located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844-848 exists and will be valuable in the management and genetic counseling of a significant number of individuals., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) with intellectual disability (ID) is a life-long debilitating condition, which is characterized by cognitive function impairment and other neurological signs. Children with ASD-ID typically attain motor skills with a significant delay. A sub-group of ASD-IDs has been linked to hyperlactacidemia and alterations in mitochondrial respiratory chain activity. The objective of this report is to describe the clinical features of patients with these comorbidities in order to shed light on difficult diagnostic and therapeutic approaches in such patients. We reported the different clinical features of children with ID associated with hyperlactacidemia and deficiencies in mitochondrial respiratory chain complex II-IV activity whose clinical presentations are commonly associated with the classic spectrum of mitochondrial diseases. We concluded that patients with ASD and ID presenting with persistent hyperlactacidemia should be evaluated for mitochondrial disorders. Administration of carnitine, coenzyme Q10, and folic acid is partially beneficial, although more studies are needed to assess the efficacy of this vitamin/cofactor treatment combination.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by a combination of reciprocal social deficits, communication impairment, and rigid ritualistic interest and stereotypies. The etiology is generally multifactorial, including genetic, immunological and/or environmental factors. A group of ASD has been linked to mitochondrial dysfunction with subsequent deficiency in energy production. Patients with ASD and mitochondrial disease often show signs and symptoms uncommon to idiopathic ASD such as cardiac, pancreatic or liver dysfunction, cardiac, growth retardation, fatigability, but in some cases semiology is different. We show two clinical cases of ASD associated to a deficiency of the mitochondrial respiratory chain (complex I+III and IV) with different clinical presentations. In one case, signs and symptoms of mitochondrial disorder were mild and the second diagnosis was attained many years after that of ASD. These findings support the recent growing body of evidence that ASD can be associated with mitochondrial disorder. Children with ASD and abnormal neurologic or systemic findings should be evaluated for mitochondrial disorder.

INTRODUCTION. Glycogen storage disease type II, or Pompe disease, is a lysosomal disease with an autosomal recessive pattern of inheritance. Late-onset Pompe disease is a progressive metabolic myopathy caused by decreased activity of the enzyme acid alpha-glucosidase (GAA), which gives rise to reduced degradation and later accumulation of glycogen in the lysosomes and cell cytoplasm. CASE REPORT. A 16-year-old Venezuelan male, diagnosed with late-onset glycogen storage disease type II, or Pompe disease, based on the patient's clinical picture and the biochemical findings. The patient presented unmistakable signs of muscular atrophy in the upper and lower limbs, as well as positive Gowers' sign. Levels of creatinkinase in serum were high. His functional respiratory capacity was diminished. The quantification of the enzymatic activity of acid alpha-glucosidase on filter paper did not show any significant decrease in activity. A molecular genetic analysis revealed the existence of two homozygotic mutations in the gene GAA, c.547-67C>G and c.547-39T>G, both on exon 2 of chromosome 17. According to the human genome database and the review that was undertaken, the changes detected in this patient represent new mutations in the acid alpha-glucosidase gene, GAA. This claim is in agreement with the clinical features and biochemical changes found in the patient. CONCLUSION. A molecular genetic study is mandatory in patients suspected of having this disease.

Autism is the prototype of generalized developmental disorders or what today are called autism spectrum disorders. In most cases it is impossible to detect a specific etiology. It is estimated that a causative diagnosis may be shown in approximately 10-37% of the cases, including, congenital rubella, tuberous sclerosis, chromosome abnormalities such as fragile X syndrome and 22q13.3 deletion syndrome, Angelman, Williams, Smith-Magenis, Sotos, Cornelia de Lange, Möbius, Joubert and Goldenhar syndromes, Ito's hypomelanosis, as well as certain cerebral malformations and several inherited metabolic disorders. The case of a 3-year old girl is described, who was considered as autistic according to the criteria established by the DSM-IV manual for psychiatric disorders. She showed a delay in psychomotor development since she was 18 months old; she pronounces very few words (10), points to some objects, does not look up and it is hard to establish eye contact with her. She has paradoxical deafness and therefore, does not respond when called or when she is given orders, she is beginning to walk. She has not convulsions. Laboratory tests showed an anion gap of 31.6 mEq/L, lactate: 2.55: mmol/L, pyruvate: 0.06 mmol/L, and elevated lactate to/pyruvate ratio: 42.5. Under optical microscopy a muscular biopsy showed a reduction of the diameter of muscular fibers. The study of energy metabolism showed a partial deficiency of complexes III and IV of the respiratory chain, which allowed us to conclude that this was a mitochondrial dysfunction with an autistic clinical spectrum.

Cryptococcus neoformans meningoencephalitis is the most common fungal central nervous system infection, in people affected by the human immunodeficiency virus. It is rare in inmunocompetent children and it is often fatal. It predominates in males at a ratio of 3 to 1. We describe the cases of two school children, one male and one female, with history of contact with pigeons (Columba livea), whose clinical symptoms were fever, headache, photophobia, diplopia, ataxia and meningeal signs, with unilateral involvement of cranial nerve VI. The diagnosis was established by the isolation of Cryptococcus neoformans in culture, staining with India ink and evidence of latex antigen agglutination in the cerebrospinal fluid. The determination of antibodies to human immunodeficiency virus and quantification of CD4, CD8 and T lymphocyte cells, were normal. In the first case, a chest X-ray showed a round mass, circumscribed in the bottom half of the left lung. A brain MRI revealed an image compatible with a nodular cryptococcoma in the parietal region. A pattern of intracranial hypertension was established, with papilledema and bilateral amaurosis, that evolved unsatisfactorily, with the subsequent death of the patient. Both were treated with amphotericin B (1 mg/Kg/day) or fluconazole (6 mg/Kg/day). The second case had a favorable evolution. The Crypotococcus neoformans is not a common fungus in inmunocompetent children. Early detection of the disease and appropriate treatment is essential to achieve a better prognosis ot the disease.

Primary hyperoxaluria is a congenital innate error of the metabolism of the amino acids, that is transmitted like an autosomal recessive character. Two types of hyperoxaluria exist: the primary type I, that corresponds to the peroxisomal enzymatic deficit of the alanine glyoxylate aminotransferase in the liver (AGT) and type II, due to the deficit of the glyoxylate reductase/hydroxypyruvate reductase deficiency (GRHPR). The primary type I (AGT) is the most frequenty. We report the case of a female infant of one month of age, that on her first day post birth, presented myoclonic convulsions and tonic spasms, both during wakefullness and sleep periods, that became more frequent and did not respond to the use of anticonvulsants. The ictal Electroencephalogram presented an intermittent activity of spikes and spike-waves of high voltage in the right hemisphere. Eight minutes after the intravenous administration of 150 mg of pyridoxine, it was observed a diminution of the epileptic activity, as well as the clinical manifestations. The determination of organic acids in urine revealed an increase in the concentration levels of oxalic acid (3064 mmol/mol of creatinine). The molecular genetic study of the AGXT gene, showed the existence of a R197Q mutation in exón 5 of the patient and her father. She received treatment with pyridoxine at a dose of 50 mg/day. When she reached the age of three months both a normal electroencephalogram and biochemistry were obtained. Although it is a rare cause of neonatal convulsions, hyperoxaluria, due to new mutations is an underdiagnosed disease by neonatologists and paediatricias.

Mitochondrial encephalopathies are a group of diseases that have as their pathogenic basis an alteration of the mitochondrial DNA (mtDNA). The MELAS phenotype (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) has been related to mutation A3243G in approximately 80% of the cases reported. MERRF (epilepsy myoclonus with ragged red fibers) has been related to mutation A8344G and A8566G of tRNA Lys. We report the case of a 7 months-old female with early clinical signs of encephalopathy associated to the A3243G mutation. Laboratory tests showed lactic acidosis and the EEG pattern was compatible with an encephalopathic process. The infant was treated with ACTH during one month, with clinical and electroencephalographic improvements. Currently, she is receiving treatment with B-vitamins, L-Carnitine and urinary alkalizing agents. It is concluded that an analysis of mtDNA must be made in infants who present convulsions, delay in their psychomotor development, lactic acidosis and an EEG pattern compatible with an encephalopathy, to rule out a mitochondrial disease.

Introduction: Landau-Kleffner syndrome is characterised by acquired aphasia and encephalographic alterations that may or may not be accompanied by epileptic seizures. AIM. To analyse the clinical and encephalographic features and response to treatment of 10 patients with Landau-Kleffner syndrome., Patients and Methods: We reviewed the patient records, encephalograms and treatment administered to patients catalogued as having Landau-Kleffner syndrome., Results: The mean age of the patients was 44 months. Of these cases, 60% presented epilepsy when the diagnosis was established and 70% were found to have epileptic status during slow-wave sleep in the encephalographic study. Results showed that 40% corresponded to variants of Landau-Kleffner syndrome. No cause of the disease could be established in any of the patients. In the neuroimaging study, only one patient displayed abnormalities in the magnetic resonance imaging of the brain. All the patients received adrenocorticotropic hormone (ACTH)-based treatment, at a dose of 1 IU/kg/day for one month, administered together with antiepileptic drugs such as valproic acid and clobazam. Convulsive seizures and epileptic status during slow-wave sleep disappeared in all the patients. In the patients without epileptic status, epileptic activity became less frequent, although it did not completely disappear. Aphasia improved considerably, which meant that all the patients were able to enroll in normal schools., Conclusions: We believe that early diagnosis, together with suitable and timely management of aphasic patients with encephalographic alterations that allow ACTH to be used at low doses, make it possible to offer an early education so as to provide maximum recovery from the disease.

Introduction: Alternating hemiplegia (AH) of childhood is a rare disease that gives rise to transient attacks of hemiplegia that may affect either side of the body indistinctly, or even both sides at the same time. Onset occurs before the age of 18 months and in some cases there are neonatal symptoms such as abnormal eye movements, especially nystagmus, and dystonic or tonic seizures. Attacks of hemiplegia, which disappear during sleep, begin before the age of one year. These symptoms can initially be taken for an epileptic disorder., Case Reports: We describe the study of two male patients whose clinical symptoms appeared at the age of 6 months, with tonic seizures, upward deviation of gaze, without loss of consciousness, which occurred with a recurrence rate of between one and two attacks a week or several times a day. They were initially treated with antiepileptic drugs (AED), although the complementary tests, including electroencephalogram (EEG), computerised axial tomography (TAC), magnetic resonance (MR) scans and metabolic tests, were all normal., Conclusions: Since, to date, no specific test has been confirmed for the disease, diagnosis is essentially clinical and by exclusion. Treatment is symptomatic using flunarizine. In one of our cases, administration of a single 10 mg/day dose this drug at night lowered the frequency of the attacks of hemiplegia. The possibility of treating a patient who is a carrier of an AH with AED makes early knowledge and identification of this disease necessary in order to be able to improve the patient's prognosis.

Introduction: Organic acidurias have long been known to cause neurological problems, such as convulsions, stupor, coma, and psychomotor and mental retardation. The organic acidurias include propionic aciduria, methylmalonic aciduria (MMA), isovaleric acidemia, lactic acidemia and glutaric acidemia type I. However, the association of MMA with electrical activity of the brain characterised by a hypsarrhythmic pattern, refractory convulsions and psychomotor retardation is very rare., Case Reports: Two patients, one male and one female, were seen to have psychomotor retardation, erratic attacks of myoclonic convulsions, hypsarrhythmic encephalographic pattern and an increase in the urinary excretion of methylmalonic acid, as shown by gas chromatography and mass spectrometry, all of which supported a diagnosis of MMA in both cases. In one patient, the brain MRI with gadolinium showed lesions compatible with brain atrophy. Protein restrictions, the administration of vitamin B12 and l carnitine re established the normal neurological state and reduced the urinary excretion of methylmalonic acid in one of them., Conclusions: To the best of our knowledge these are the first cases of MMA that have been seen accompanied by hypsarrhythmia. The rareness of this clinical presentation with the characteristics described above make us suspect that we are dealing with a new clinical syndrome.