Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
Orphanet J Rare Dis ; 15(1): 252, 2020 09 21.
Article in English | MEDLINE | ID: mdl-32958024

ABSTRACT

BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare condition characterized by an alveolar hypoventilation due to a deficient autonomic central control of ventilation and a global autonomic dysfunction. Paired-like homeobox 2B (PHOX2B) mutations are found in most of the patients with CCHS. In recent years, the condition has evolved from a life-threatening neonatal onset disorder to include broader and milder clinical presentations, affecting children, adults and families. Genes other than PHOX2B have been found responsible for CCHS in rare cases and there are as yet other unknown genes that may account for the disease. At present, management relies on lifelong ventilatory support and close follow up of dysautonomic progression. BODY: This paper provides a state-of-the-art comprehensive description of CCHS and of the components of diagnostic evaluation and multi-disciplinary management, as well as considerations for future research. CONCLUSION: Awareness and knowledge of the diagnosis and management of this rare disease should be brought to a large health community including adult physicians and health carers.


Subject(s)
Hypoventilation/congenital , Sleep Apnea, Central , Adult , Child , Homeodomain Proteins/genetics , Humans , Hypoventilation/diagnosis , Hypoventilation/genetics , Hypoventilation/therapy , Mutation , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/genetics , Sleep Apnea, Central/therapy , Transcription Factors/genetics
2.
Sleep Sci ; 7(1): 53-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-26483902

ABSTRACT

Narcolepsy, a chronic disorder of the sleep-wake cycle of multifactorial etiology, is characterized by excessive daytime sleepiness, often associated with cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis. Both early clinical suspicion and therapeutic approach are essential for promotion of cognitive development and social integration of these children. The authors present a descriptive retrospective study of a series of eight children in whom symptoms first started between 6.8 and 10.5 years of age. Diagnostic delay ranged from 4 months to 2 years. One child had H1N1 flu vaccination eight months before the clinical onset. The first multiple sleep latency test was positive in 6 of 8 cases. All cases were treated with methylphenidate, and venlafaxine was associated in 4 of them. In one case the initial therapy was exclusively behavioral. In all cases, symptomatic improvement, better school performance and social integration were achieved after therapeutic adjustment.

3.
Acta Med Port ; 26(4): 361-70, 2013.
Article in Portuguese | MEDLINE | ID: mdl-24016645

ABSTRACT

INTRODUCTION: Pompe disease or glycogen storage disease type II is an autosomal recessive disorder due to acid maltase deficiency. It is a rare disease with a prevalence of 1/40.000 in the dutch and african-american populations and 1/46000 in the australian population. There are three forms of clinical presentation (infantile-onset, childhood-onset and adult-onset), although the disease presents as a continuum of clinical phenotypes. Enzyme replacement therapy is available in Portugal since 2006. MATERIALS AND METHODS: The clinical files of four patients (two sisters) were analyzed retrospectively. RESULTS: In all, disease presented in the second year of life and the time to diagnosis ranged from two to eleven years. At diagnosis, all presented myopathic features with a delay in motor skills achievement and two had myocardium hypertrophy. Clinical suspicion arose as the result of respiratory failure during infection in two patients. Plasma creatine kinase and aminotransferases levels were increased in all. All patients progressed to pulmonary restrictive syndrome with chronic respiratory failure. The diagnosis was based on reduced activity of acid maltase in fibroblasts: 0 to 1.5% of the lower normal value. Muscle biopsy, performed in three patients, showed lysosomal glycogen accumulation. A c.1064T > C mutation in exon 6 of GAA (glucosidase-alpha-acid) gene was found in all patients, in homozygosity in one. In the sisters, it was associated to c.1666A > G and c.2065G > A mutations in exons 12 and 15, respectively and in the youngest patient, to c.380G > T mutation in exon 2. All patients started enzyme replacement therapy as soon as it became available, with good tolerance. The youngest patient died. The surviving patients maintain ventilatory support measures and physiotherapy. The oldest patient is wheelchair ridden and her sister keeps independent walking. The youngest uses a walking aid. CONCLUSIONS: Our cases are clinically included in the juvenile form of Pompe Disease. Pompe disease should be suspected in progressive myopathies at any age, especially those involving limb-girdle and respiratory muscles and in small infants with cardiomyopathy. High creatine kinase is a sensitive, although nonspecific, marker. Given the great variability of the genetic findings, demonstration of reduced activity of acid maltase (in leukocytes or other tissues) remains the diagnosis cornerstone of this rare disorder.


Introdução: A doença de Pompe ou glicogenose tipo II é uma doença autossómica recessiva por deficiência de maltase ácida. É uma entidade rara, com prevalência de 1/40.000 nas populações holandesa e afro-americana e 1/46000 na população australiana. Embora se distingam três formas de apresentação (infantil, juvenil e do adulto), observa-se um amplo espectro clínico. Em Portugal está disponível terapêutica enzimática de substituição desde 2006.Material e Métodos: Fez-se o estudo retrospetivo de quatro doentes (duas das quais irmãs), baseado na revisão dos processos clínicos.Resultados: Em todas, a doença manifestou-se no segundo ano de vida. O tempo até ao diagnóstico variou entre dois e onze anos. Aquando do diagnóstico, todas apresentavam miopatia com atraso de aquisições motoras e em duas havia hipertrofia miocárdica. A suspeita clínica surgiu por insuficiência respiratória em contexto infeccioso em duas doentes. Em todas havia elevação da creatina quinase e das aminotransferases. Todas evoluíram com insuficiência respiratória crónica por síndrome restritiva. O diagnóstico foi baseado na diminuição da atividade da maltase ácida em fibroblastos (0 a 1,5% do limite inferior do normal). Na biópsia muscular, realizada em três doentes, demonstrou-se acumulação lisossómica de glicogénio. Todas apresentavam a mutação c.1064T > C no exão 6 do gene GAA (glucosidase-alpha-acid), em homozigotia numa delas, associada às mutações c.1666A > G no exão 12 e c.2065G > A no exão 15 nas duas irmãs e à mutação c.380G > T no exão 2 na doente mais nova. Todas iniciaram terapia enzimática de substituiçãologo que disponível, com boa tolerância. A doente mais jovem faleceu pouco depois. As outras mantêm medidas de suporteventilatório e fisioterapia, deslocando-se a mais velha, em cadeira de rodas, mantendo a irmã marcha independente e necessitando a mais nova de andarilho.Conclusão: Os nossos casos incluem-se clinicamente na forma juvenil da doença de Pompe. A hipótese de doença de Pompe deve ser considerada em lactentes com miocardiopatia e nas miopatias progressivas, especialmente as das cinturas e dos músculos respiratórios em qualquer idade. A elevação da creatina quinase é um dado sensível, embora inespecífico. Dada a grande variabilidade dos achados genéticos, a demonstração da redução da atividade da maltase ácida continua a ser o pilar do diagnóstico.


Subject(s)
Glycogen Storage Disease Type II/therapy , Adolescent , Child, Preschool , Female , Glycogen Storage Disease Type II/diagnosis , Humans , Retrospective Studies , Young Adult
4.
Acta Med Port ; 24(3): 399-404, 2011.
Article in Portuguese | MEDLINE | ID: mdl-22015026

ABSTRACT

INTRODUCTION: Visceral Leishmaniasis (VL) is a systemic infection, endemic in many parts of the world, including Portugal. The aim is to review all cases of VL admitted to our hospital. PATIENTS AND METHODS: Retrospective analysis of all cases of VL admitted to a Level III Paediatric Hospital, between January 1990 and December 2009 (20 years). Demographic, epidemiological, clinical, laboratorial, therapeutic and follow-up data were analysed. RESULTS: During the study period, 54 children were admitted with VL, three of which were excluded from the study due to incomplete clinical records. The mean age was 27 months (seven months - twelve years) and 53% were female. Two thirds of the cases were diagnosed during Spring and Summer. The mean time for diagnosis was 31 days (2-188 days). The most common clinical findings were splenomegaly (100%), fever (96%), pallor (90%) and hepatomegaly (82%). Bone marrow aspiration was performed in all children, with amastigotes identified in 73% of the cases. Indirect immunofluorescence was performed in 30 cases, being positive in 29 (97%). All were treated with meglumine antimoniate. Three children relapsed during the first year after the initial episode. A 17 months-old child died due to cardiac failure. CONCLUSIONS: The early diagnosis of VL is essential to carry out prompt management and prevent potential fatal complications. In our analysis, the management with meglumine antimoniate resulted in an overall favourable outcome.


Subject(s)
Leishmaniasis, Visceral , Child , Child, Preschool , Female , Hospitals, Pediatric , Humans , Infant , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/epidemiology , Male , Referral and Consultation , Retrospective Studies
5.
Hum Mutat ; 29(5): 770, 2008 May.
Article in English | MEDLINE | ID: mdl-18407552

ABSTRACT

Homozygosity for a dominant allele is relatively rare and preferentially observed in communities with high inbreeding. According to the definition of true dominance, similar phenotypes should be observed in patients heterozygous and homozygous for a dominant mutation. However, the homozygous phenotype usually tends to be more severe than the heterozygous one. In these cases, the wild-type and mutant alleles are semi-dominant. Here we report a patient with a Congenital Central Hypoventilation Syndrome (CCHS) phenotype and homozygosity for a PHOX2B gene mutation leading to an alanine expansion shorter than the threshold hitherto observed in CCHS patients with a heterozygous mutation. This observation adds the concept of mutational threshold per se to the discussion about dominant and recessive alleles.


Subject(s)
Homeodomain Proteins/genetics , Homozygote , Mutation , Sleep Apnea, Central/genetics , Transcription Factors/genetics , Alanine/genetics , Alleles , Female , Genes, Dominant , Humans , Infant, Newborn , Male , Pedigree
6.
Rev Port Pneumol ; 13(5): 721-7, 2007.
Article in Portuguese | MEDLINE | ID: mdl-17962890

ABSTRACT

The incidence of the syndrome may be greater than is suspected. Patients present with recurrent respiratory infections and bronchiectasis. The symptoms are non-specific and indistinguishable from those of other chronic respiratory diseases. The diagnosis is often made several years after the first clinical complaints. The authors perform a brief review of the literature and report two cases of Mounier-Kuhn syndrome. One of the patients was diagnosed in childhood and the other in the fourth deca- de of life.


Subject(s)
Respiratory Tract Infections/etiology , Tracheobronchomegaly/complications , Adolescent , Adult , Female , Humans , Male , Recurrence
7.
Rev Port Pneumol ; 11(5): 443-55, 2005.
Article in English, Portuguese | MEDLINE | ID: mdl-16288344

ABSTRACT

The deterioration of the respiratory function in children suffering from degenerative neuromuscular disease is the main cause of the high mortality rate associated with these diseases. Noninvasive ventilation (NIV) has reduced the morbidity and mortality due to respiratory insufficiency in these children. However, the use of support ventilation in some cases of spinal muscular atrophy (SMA) is still controversial. A retrospective study of 22 patients suffering from SMA who were followed up in the Paediatric Hospital of Coimbra is presented: 7 of type I, 11 of type II, and 4 of type III. In 17 of these cases, non-invasive ventilation by mask was begun, and in 3 of them NIV was applied for prophylactic purposes. The 7 children with SMA type I began NIV when they were 13 months of age on average (3 months-3 years); 5 of them died, between 1 and 15 months after the beginning of the ventilation. Of the 11 children with SMA type II, 8 were submitted to NIV and one died 22 months later. Three of the children in this group began NIV in a prophylactic way, and in all of them a decrease in the thoracic deformity was observed. Of the 4 patients of type III, 2 of them were submitted to non-invasive ventilation. In all of the symptomatic cases, a decrease in the frequency and severity of respiratory infections was observed, after ventilation was started. The respiratory support with NIV may improve the quality of life of children suffering from SMA as well as prolong their life expectancies. In SMA type I, whose clinical manifestations are precocious and whose prognostic is very serious, the application of this support has been debated.


Subject(s)
Muscular Atrophy, Spinal/therapy , Respiration, Artificial , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Respiration, Artificial/methods , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...