Zespół Joubert i schorzenia pokrewne

The cerebellum plays a role not only in motor control but also in motor learning and cognition. Joubert syndrome is a rare heterogeneous inherited genetic disorder characterized by ataxia, hypotonia, developmental delay, and at least one of the following features: neonatal respiratory disturbances or abnormal eye movement. The estimated frequency of Joubert syndrome in the United States is around 1 : 100 000. The term Joubert syndrome and related disorders (JSRD) has been recently coined to describe all disorders presenting with molar tooth sign on brain neuroimaging. Joubert syndrome is believed to be a representative of a new group of disorders named ciliopathies. The identification of seven causal genes (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67/MKS3, ARL13B, CC2D2A) has led to substantial progress in the understanding of the genetic basis of Joubert syndrome. The authors focus on clinical presentation of JSRD, differential diagnosis and molecular background.Móżdżek odgrywa istotną rolę w kontroli nie tylko funkcji ruchowych, ale także procesów poznawczych. Zespół Joubert jest rzadkim heterogennym schorzeniem uwarunkowanym genetycznie, charakteryzującym się występowaniem ataksji, hipotonii, opóźnienia rozwoju psychoruchowego, a także jednej z następujących cech: zaburzeń oddychania w okresie noworodkowym lub nieprawidłowych ruchów gałek ocznych. Szacowana częstość występowania zespołu Joubert i zespołów pokrewnych w USA wynosi ok. 1 : 100 000. Zespół Joubert i zespoły pokrewne obejmują schorzenia, w których występuje obraz „zęba trzonowego” w badaniu obrazowym układu nerwowego. Zespół Joubert stanowi przykład nowej grupy chorób nazywanych ciliopatiami. Identyfikacja 7 genów (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67/MKS3, ARL13B, CC2D2A) poczyniła znaczący postęp w zrozumieniu genetycznych podstaw zespołu Joubert. Autorzy prezentują objawy kliniczne zespołu Joubert i schorzeń pokrewnych, diagnostykę różnicową i podłoże genetyczne

Spektroskopia rezonansu magnetycznego i badania molekularne w nowej mutacji powodującej niedobór transkarbamylazy ornitynowej c.802AG w egzonie 8 (p.Met268Val)

Abstract Ornithine transcarbamylase (OTC) deficiency, an X-linked, semidominant disorder, is the most common inherited defect in ureagenesis, resulting in hyperammonaemia type II. The OTC gene, localised on chromosome X, has been mapped to band Xp21.1, proximate to the Duchenne muscular dystrophy (DMD) gene. More than 350 different mutations, including missense, nonsense, splice-site changes, small deletions or insertions and gross deletions, have been described so far. Almost all mutations in consensus splicing sites confer a neonatal phenotype. Most mutations in the OTC gene are ‘private’ and are distributed throughout the gene with a paucity of mutation in the sequence encoding the leader peptide (exon 1 and beginning of exon 2) and in exon 7. They have familial origin or occur de novo. Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remainder probably occur within the introns or in regulatory domains. The authors present a 4-year-old boy with the unreported missense mutation c.802A>G. The nucleotide transition leads to amino acid substitution Met to Val at codon 268 of the OTC protein.Streszczenie Niedobór transkarbamylazy ornitynowej (OTC), dziedziczony w sposób sprzężony z chromosomem X, to najczęstsza jednostka chorobowa ureagenezy stanowiąca hiperamonemię typu II. Gen OTC zlokalizowany jest w obrębie chromosomu X, zmapowany w rejonie Xp21.1, proksymalnie do genu dystrofii mięśniowej Duchenne'a (gen DMD). Do chwili obecnej opisano ponad 350 różnych mutacji typu zmiany sensu, braku sensu, zmiany ramki odczytu czy małych delecji lub insercji albo dużych delecji. Prawie wszystkie mutacje związane ze zmianą ramki odczytu wywołują fenotyp noworodkowy. Większość mutacji w genie OTC to mutacje prywatne z dystrybucją w obrębie całego genu oraz z brakiem mutacji w sekwencji kodującej główne białko (egzon 1 lub początek egzonu 2) i w egzonie 7. Mają one pochodzenie rodzinne lub pojawiają się de novo. Sekwencjonowanie całej ramki odczytu oraz granic egzon/intron pozwala na wykrycie 80% mutacji u pacjentów z rozpoznanym OTC. Pozostałe mutacje prawdopodobnie występują w obrębie intronów lub domen regulatorowych. Autorzy prezentują przypadek 4-letniego chłopca z nieopisaną mutacją typu zmiany sensu c.802A> G. Przemieszczenie nukleotydów prowadzi do zamiany metioniny na walinę w kodonie 268 białka OTC

Clinical and neuropathological picture of familial encephalopathy with bifunctional protein deficiency

Peroxisomal diseases are a heterogeneous group of genetic metabolic disorders which are caused by incorrect biogenesis of peroxisomes or a defect in activity of particular enzymes located in those organelles. D-bifunctional protein (D-BP) deficiency belongs to the second group of peroxisomal diseases characterised by dysfunction of a single peroxisomal enzyme. Bifunctional protein is a catalyst in the second and third stage of the \beta-oxidation of fatty acids. Gene locus of bifunctional protein deficiency comprises chromosomes 5q2 and 3p23-p22. The authors present two siblings with progressing family encephalopathy. In the younger brother the diagnosis of a bifunctional protein deficiency was made. The girl died before a diagnosis was made; however, due to the presence of a very similar clinical condition a suspicion arises that the girl had a peroxisomal disease. In the siblings were ascertained characteristic dysmorphic features, delayed psychomotor development, polymorphic epileptic seizures and generalized muscular hypotonia with areflexia. The neuropathological findings were consistent in general with MRI findings showing features of hypomyelination. Also neuron heterotopias that were found in autopsy are a form of pathology typical for D-BP

Clinical and neuropathological picture of ethylmalonic aciduria : diagnostic dilemma

Increased ethylmalonic acid (EMA) in urine is a non-specific finding, and is observed in a number of inborn errors of metabolism, as well as in individuals who carry one of two common polymorphisms identified in the SCAD coding region. The authors present an 8-month-old girl with a suspicion of neuroinfection, although the clinical presentation led to diagnosis of ethylmalonic aciduria. From the neuropathological point of view the most remarkable changes were observed in the brain cortex, which was diffusely damaged practically in all regions of the brain. Of note, the most severe destruction was observed in the deepest regions of the sulci. The cortex of the affected regions showed no normal stratification and its structure was almost totally replaced by a form of "granulation tissue" with a markedly increased number of capillaries. To the authors’ knowledge this is the first clinical report of ethylmalonic aciduria with brain autopsy findings

The content of serotonin cells in duodenal biopsies of autistic patients

AbstractIntroductionAutistic spectrum disorders (ASD) don’t have the same etiology. Platelet hyperserotonemia remain the most common neurochemical abnormality in these patients. The main producer and storage of peripheral serotonin are enteric enterochromaffin cells – serotonin cells. Platelet hyperserotonemia may result from disorders in the synthesis and/or release of enteric serotonin. An increased number of people with ASD have gastrointestinal disorders. Some of them have a serotonergic background.AimThe aim was to assess the serotonin cells in the duodenal mucosa of patients with ASD.Material and methodsStudy group: 30 children with ASD, including 73% with duodenitis chronica. Control group (patients without ASD): 45 patients, 56% with duodenitis chronica. Immunohistochemical assessment of the number of serotonin cells was performed.’ResultsChildren with ASD and duodenitis have fewer serotonin cells than autistic children with a normal picture of the duodenum. Children with ASD and chronic duodenitis have fewer serotonin cells than patients from the control group. Patients from the control group, suffering from chronic duodenitis have an increased number of serotonin cells in relation to children without inflammatory lesions in the duodenum.ConclusionsThe serotonergic profiles of the GI tract of autistic patients and their peers without autistic symptoms are different. In the course of chronic duodenitis in patients with ASD the number of serotonin cells falls while in persons without autistic features it increases significantly. Chronic duodenitis contributes to an increase in the number of serotonin cells in persons without autistic features while decreasing it in patients with ASD