Sodium Channel Myotonia and a Novel Gly701Asp Mutation in the SCN4A Gene: From an Ophthalmological Symptom to a Familial Disease.

A six-month-old female child came to an ophthalmology consultation because of a convergent strabismus, myotonia of the orbicularis muscles and difficulty walking in cold environments. Further investigation identified a family history of muscular myotonia in the father, grandmother and uncle. The father also presented with ocular myotonia. The child and family members underwent genetic testing, which was negative for CLCN1 mutations but was positive for a novel heterozygotic Gly701Asp mutation in the SCN4A gene, compatible with sodium channel myotonia. The non-dystrophic myotonias are caused by dysfunction of key skeletal muscle ion channels. Before the advent of DNA sequencing, non-dystrophic myotonias were differentiated based on clinical phenotypes. Sodium channel myotonia disorders are classically of dominant inheritance, in which eye closure myotonia is the most frequent manifestation. Over 40 different mutations have been reported in the SCN4A gene. The Gly701Asp mutation in exon 13 identified in this family has not been described before.

A Challenging Case: Botulism in a Toddler.

Botulism is a life-threatening, rapidly progressive neuroparalytic disease caused by one of the most potent toxins known, botulinum toxin. It manifests as flaccid and symmetrical descending paralysis that can affect both cranial and peripheral nerves. The only specific treatment available is the administration of botulinum antitoxin. We present the case of a three-year-old boy who had gastrointestinal symptoms and had ingested garden soil/dust at a construction site before the onset of cranial nerve palsy, which manifested as dysphagia in swallowing liquid and solid food and bilateral progressive ptosis. Early suspicion of botulism and treatment with botulinum antitoxin resulted in complete neurologic recovery. This case highlights the importance of a careful history and neurologic examination to avoid misdiagnosis. Administration of botulinum antitoxin should not be delayed until the diagnosis is confirmed and clinicians should be aware that this approach can be life-saving.

Cerebral venous thrombosis in adolescence: Looking beyond the obvious.

Behçet's disease (BD) is a rare systemic vasculitis with multisystemic involvement. Neurological involvement, called neuro-Behçet's disease (NBD), mostly involves the central nervous system and cerebral venous thrombosis (CVT) is the predominant neurological manifestation in the pediatric age. A 12-year-old female with a past medical history of a CVT, without an identifiable etiology, was admitted with a five-day right fronto-orbital headache. Neuroimage showed a subacute thrombosis of a right superficial sylvian vein, with indirect signs of intracranial hypertension and no imaging signs of vasculitis. Prothrombotic screening and immunologic study were normal. She was started on acetazolamide and hypocoagulation with progressively improving. She had a history of frequent oral aphthae and an episode of a genital ulcer three months before admission. Pathergy test was negative. HLA-B51 was positive. She was diagnosed with NBD and started therapy with colchicine and infliximab. After discharge, the patient remains without symptoms, hypocoagulated, and on infliximab regimen, without complications to report. This case, only diagnosed in the second episode of CVT, is paradigmatic of the difficulty in establishing the diagnosis of BD.

Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients.

BACKGROUND: The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype-phenotype correlations. RESULTS: The mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants. CONCLUSION: The identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.

Pertussis with severe pulmonary hypertension in a newborn with good outcome - case report.

In spite of the availability and widespread use of vaccines, pertussis is far from controlled. Newborns and infants too young to be fully vaccinated, born from mothers with low antibody titers to Bordetella pertussis, are highly susceptible to infection and at risk of severe disease and death. Pertussis associated with pulmonary hypertension in the newborn is often fatal. The authors report a clinical case of severe pertussis -induced respiratory failure associated to severe pulmonary hypertension in a neonate successfully treated with sildenafil and inhaled nitric oxide.

Rib osteomyelitis in a pediatric patient case report and literature review.

Rib osteomyelitis is a very rare form of childhood osteomyelitis. We describe a case of a 9-year-old child with an osteomyelitis of the rib due to Staphylococcus aureus and review 57 cases reported in the literature. This case demonstrates that the diagnosis of this uncommon disease requires a high index of suspicion due to its rarity and nonspecific signs.

[Neurofibromatosis type 1 - a malignant evolution in pediatric age]. / Neurofibromatose tipo 1 - uma evolução maligna em idade pediátrica.

Neurofibromatosis type 1 is an autosomal dominant disease affecting one in 3000 to one in 4000 people, with a great variability of clinical expression. Individuals affected with neurofibromatosis type 1 have an increased risk of developing both benign and malignant tumors, supporting the classification of tumor predisposition syndrome. The most common tumor is the neurofibroma, a heterogeneous benign nerve sheath tumor, which represents the primary clinical characteristic of neurofibromatosis. The case reported refers to a adolescent boy with neurofibromatosis type 1 diagnosed at 20 months, who presented progressive growth of dorsal and lumbar intraspinal tumors since six years of age and diagnosis of malignant nerve sheath tumors at 17 years of age. In addition to describing a rare presentation of neurofibromatosis, because of location and early onset of complications, the authors discuss the difficulties of the therapeutic approach of this case.