ABSTRACT
The mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is characterized by the association of gastrointestinal and neurological symptoms. It is a rare autosomal recessive mitochondrial disorder with multiple mitochondrial DNA deletions and/or depletion. It is caused by thymidine phosphorylase (TP) gene mutations resulting in a complete abolition of TP activity. We tested 31 unrelated patients presenting either with a complete MNGIE syndrome (8 patients), a severe intestinal pseudo-obstruction (10 patients), and multiple deletions and/or depletion of mitochondrial DNA (13 patients). All the tested patients presenting with a complete MNGIE had increased thymidine levels in plasma and urine, and no TP activity. The group with pseudo-obstruction syndrome had normal or partial reduction of TP activity. We found pathogenic mutations on TP gene only in the MNGIE syndrome group: all the MNGIE patients were compound heterozygous or homozygous for mutations in the TP gene. Eight of these mutations are yet unreported, confirming the lack of genotype/phenotype correlation in this syndrome. Enzymatic activity and thymidine level are thus rapid diagnosis tests to detect MNGIE affected patients prior to genetic testing for patients with gastrointestinal symptoms.
Subject(s)
Mitochondrial Encephalomyopathies/genetics , Mutation , Thymidine Phosphorylase/genetics , Adult , Child , DNA, Mitochondrial/genetics , Humans , Intestinal Pseudo-Obstruction/genetics , Sequence Deletion , Syndrome , Thymidine/blood , Thymidine/urine , Thymidine Phosphorylase/metabolismABSTRACT
Factor XIII (FXIII) deficiency is a rare autosomal recessive congenital disorder of haemostasis, associated with a high risk of intracranial haemorrhage. Intracranial haemorrhage can result in neurological sequelae including seizure disorders. In some cases, medically intractable epilepsy led to epilepsy surgery. Little has been reported on the management of FXIII deficiency during surgery, and there is only a few data on the management, safety and efficacy of epilepsy surgery in the patients with haemostatic disorder. We report here an epilepsy neurosurgery in a case of severe FXIII deficiency.
Subject(s)
Epilepsy, Temporal Lobe/surgery , Factor XIII Deficiency/complications , Factor XIII/therapeutic use , Hemostasis, Surgical/methods , Child, Preschool , Epilepsy, Temporal Lobe/diagnosis , Epilepsy, Temporal Lobe/etiology , Factor XIII Deficiency/drug therapy , Humans , Magnetic Resonance Imaging , Male , Neurosurgical ProceduresABSTRACT
We report the case of a female suffering from resistant partial seizures, which were related to 'cryptogenic' epilepsy, as the cerebral cortex was considered normal on the initial MRI images. As her son is mentally retarded and has a pachygyria, the doublecortin gene, usually involved in band heterotopia or lissencephaly, was screened for mutations. A missense mutation was identified, shared by both the son and his mother, and a subtle discontinuous subcortical heterotopia was subsequently detected on the mother's MRI. The pathophysiology of epilepsy in this woman is discussed in the light of the role of doublecortin, not only in neuronal migration, but also in axonal growth and dendritic connectivity.
Subject(s)
Cerebral Cortex/abnormalities , Epilepsy, Complex Partial/etiology , Neuropeptides/genetics , Point Mutation/genetics , 1-Alkyl-2-acetylglycerophosphocholine Esterase , Adult , Cerebral Cortex/physiopathology , Child, Preschool , Doublecortin Domain Proteins , Epilepsy, Complex Partial/genetics , Epilepsy, Complex Partial/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Microtubule-Associated Proteins/geneticsABSTRACT
Angelman's syndrome is an association of severe mental retardation with absence of language, ataxia, convulsions and hyperactive, joyful behaviour with frequent bouts of laughing. Genetic diagnosis is possible in about 80% of cases. No cardiovascular abnormalities have been described in this syndrome to date. The authors report the cases of three children with Angelman's syndrome who presented with severe malaise due to increased vagal tone. The age of onset of symptoms was between 20 months and 8 years. One of the children had malaises triggered by bouts of laughing. The diagnosis was confirmed in all three cases by the results of Holter 24 hour ECG recording and oculo-cardiac reflex. The treatment chosen was Diphemanil (Prantal) in the two patients under 2 years of age (after failure of a trial of betablockers in one case) and Disopyramide for the oldest child with excellent results in all cases. However, one child died suddenly at the age of 6, two years after stopping diphemanil. Based on these observations, the authors suggest that all malaises in patients with Angelman's syndrome should be investigated by Holter ECG and oculo-cardiac reflex (or tilt test). In view of the potential gravity of the syncopal attacks, long-term medical treatment seems to be justified.
Subject(s)
Angelman Syndrome/physiopathology , Dipyridamole/therapeutic use , Parasympatholytics/therapeutic use , Piperidines/therapeutic use , Vagus Nerve/physiopathology , Vasodilator Agents/therapeutic use , Age of Onset , Angelman Syndrome/therapy , Child , Electrocardiography, Ambulatory , Female , Humans , Infant , Male , Reflex, OculocardiacABSTRACT
The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by major abnormalities of eyes, nervous system, and kidneys. Mutations in the OCRL1 gene have been associated with the disease. OCRL1 encodes a phosphatidylinositol 4, 5-biphosphate (PtdIns[4,5]P2) 5-phosphatase. We have examined the OCRL1 gene in eight unrelated patients with OCRL and have found seven new mutations and one recurrent in-frame deletion. Among the new mutations, two nonsense mutations (R317X and E558X) and three other frameshift mutations caused premature termination of the protein. A missense mutation, R483G, was located in the highly conserved PtdIns(4,5)P2 5-phosphatase domain. Finally, one frameshift mutation, 2799delC, modifies the C-terminal part of OCRL1, with an extension of six amino acids. Altogether, 70% of missense mutations are located in exon 15, and 52% of all mutations cluster in exons 11-15. We also identified two new microsatellite markers for the OCRL1 locus, and we detected a germline mosaicism in one family. This observation has direct implications for genetic counseling of Lowe syndrome families.
Subject(s)
Mosaicism , Oculocerebrorenal Syndrome/genetics , Phosphoric Monoester Hydrolases , Proteins/genetics , Amino Acid Sequence , Female , Genetic Testing , Haplotypes , Heterozygote , Humans , Male , Microsatellite Repeats , Models, Genetic , Molecular Sequence Data , Mutation , Pedigree , Sequence Homology, Amino AcidABSTRACT
Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (approximately 70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counseling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.
Subject(s)
Connexins/genetics , Deafness/genetics , Sequence Deletion , Australia/epidemiology , Connexin 26 , Consanguinity , Deafness/epidemiology , France/epidemiology , Genetic Linkage , Humans , Lebanon/epidemiology , New Zealand/epidemiology , Prevalence , Tunisia/epidemiology , United Kingdom/epidemiologySubject(s)
Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/surgery , Cerebral Palsy/etiology , Echoencephalography , Electroencephalography , Epilepsy, Generalized/etiology , Female , Follow-Up Studies , Humans , Hydrocephalus/etiology , Hydrocephalus/surgery , Infant, Newborn , Male , Ventriculoperitoneal ShuntABSTRACT
The main goal of the M4 protocol was to evaluate the efficacy of treatment excluding supratentorial radiation in patients with newly diagnosed medulloblastoma. All patients underwent surgical resection and received postoperative chemotherapy. Chemotherapy was adapted to the initial staging and prognostic factors (Group A: good-risk; Group B: poor-risk). Chemotherapy was started early after surgery, and consisted of two courses of the "eight drug in one day" regimen and two courses of high dose methotrexate. Radiotherapy was delayed until 5 (Group B) to 7 (Group A) weeks after the first course of chemotherapy. Radiotherapy was administered only to the posterior fossa and the spinal axis. Only 3/16 patients (18%) are alive and disease-free with a mean follow up of 6 years. The site of progression was supratentorial in 9 out of 13 patients and three patients had spinal and/or cerebrospinal fluid relapses. Only one patient had isolated posterior fossa relapse. The mean time to relapse was 484 days. We conclude that the chemotherapy regimens used in the M4 protocol do not allow the reduction of irradiation fields in patients with cerebellar medulloblastoma. In spite of long-term side effects on neurocognitive functions, supratentorial radiotherapy should remain a major component of medulloblastoma treatment.
Subject(s)
Cerebellar Neoplasms/therapy , Medulloblastoma/therapy , Methotrexate/therapeutic use , Adolescent , Cerebellar Neoplasms/mortality , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Male , Medulloblastoma/mortality , Methotrexate/adverse effects , Neoplasm Recurrence, Local , Radiotherapy/adverse effects , Radiotherapy Dosage , Survival RateABSTRACT
Iron salt poisoning has been reported in a 7-year-old child. Desferioxamine was used for 6 days; systemic toxicity remained moderate. The clinical course was marked by gastro-intestinal symptoms and gastric stricture. The treatment principles for iron salt poisoning are reviewed.
Subject(s)
Ferric Compounds/poisoning , Gastric Outlet Obstruction/chemically induced , Anti-Bacterial Agents/therapeutic use , Chelation Therapy , Child , Chlorides , Deferoxamine/administration & dosage , Deferoxamine/therapeutic use , Gastrectomy , Gastric Lavage , Gastric Outlet Obstruction/complications , Gastric Outlet Obstruction/drug therapy , Humans , Intestinal Perforation/etiology , Intestinal Perforation/surgery , Male , Pneumonia, Aspiration/drug therapy , Pneumonia, Aspiration/etiologyABSTRACT
Prenatal diagnosis of cystic fibrosis established by study of RFLPs flanking the gene and, since 1989, by direct detection of the major mutation delta F508 is now widely used. However, there are still some indications of prenatal diagnosis by microvillar intestinal enzymes analysis. We propose a prenatal diagnosis strategy which combines both methods. This diagnosis strategy is applied to families with a 1/4 to 1/200 risk. Screening of delta F508 in the general population is discussed.
Subject(s)
Cystic Fibrosis/diagnosis , Prenatal Diagnosis/methods , Clinical Enzyme Tests , Cystic Fibrosis/genetics , Female , Humans , Mutation/genetics , Polymorphism, Restriction Fragment Length , PregnancyABSTRACT
Primary intra-cranial germ-cell tumors are a rare and heterogeneous group of neoplasms, identical to germ-cell tumors of gonads and other organs. These tumors arise along the midline, from the supra-sellar cistern to the pineal gland, and have neurological, ophthalmological, and endocrinological expression. The diagnosis is established by detection of increased levels of tumoral markers and/or by histological examination. The treatment includes chemotherapy, radiotherapy and surgery.
Subject(s)
Brain Neoplasms/diagnosis , Central Nervous System Diseases/pathology , Neoplasms, Germ Cell and Embryonal/pathology , Nervous System Neoplasms/pathology , Brain Neoplasms/pathology , Central Nervous System Diseases/diagnosis , Central Nervous System Diseases/therapy , Child , Humans , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/therapy , Nervous System Neoplasms/diagnosis , Nervous System Neoplasms/therapyABSTRACT
Gliomas involving the brain stem represent 10% of pediatric central nervous system neoplasms. They result in multiple cranial nerve involvement, long tracts signs, cerebellar signs, usually with no evidence of raising in intracranial pressure. The diagnosis is established by computed tomographic scan and magnetic resonance imaging. Classic management consists in conventional radiation therapy but the prognosis is very dismal with a five year survival rate about 30%.
Subject(s)
Brain Neoplasms/diagnosis , Brain Stem , Glioma/diagnosis , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/therapy , Child , Glioma/diagnostic imaging , Glioma/therapy , Humans , Magnetic Resonance Imaging , RadiographyABSTRACT
Three female patients with Menkes syndrome are described. Clinically, they have typical Menkes syndrome. Biochemically, they have significantly increased 64Cu-uptake in cultured fibroblasts. The chromosomal analysis was normal for two of the patients and abnormal for one patient (45X/46XX mosaicism).
Subject(s)
Gene Expression Regulation/physiology , Menkes Kinky Hair Syndrome/genetics , Phenotype , Sex Chromosome Aberrations/genetics , X Chromosome , Child, Preschool , Female , Genetic Carrier Screening , Humans , Infant , Karyotyping , Menkes Kinky Hair Syndrome/diagnosis , Prenatal DiagnosisABSTRACT
The authors report on a boy and his mother showing signs of hypoglycemia due to hypersensitivity to leucine that is related to a that dominant autosomal. The cyclic inheritance glycemia test shows hyperinsulism; oral as well as intravenous loading dose of leucine tests showed that this hyperinsulism is due to hypersensitivity to leucine. The clinical picture, outcome of the disease dietary and medical treatment with diazoxide, and the role of GIP in insulin secretion is discussed.
Subject(s)
Drug Hypersensitivity/complications , Hypoglycemia/etiology , Leucine , Adult , Female , Humans , Hypoglycemia/blood , Hypoglycemia/genetics , Infant , Insulin/blood , MaleABSTRACT
The authors report 13 cases of osteoarticular infection observed during the first month of life. The origin was iatrogenic in 7 cases. The diagnosis was based on local inflammatory signs and standard X-ray. The joints most often affected were the hip (8 out of 19 localizations) and the ankle (5/19). The causative bacteria was mostly isolated from blood culture (10/13 cases) and was staphylococcus aureus in 11 cases. Treatment included prolonged antibiotic-therapy for 1-4 months, plus evacuation by joint punctures and immobilization of the affected limb with a plaster or traction. Functional sequellae were observed in 3 children and essentially concerned the hip.
Subject(s)
Bone Diseases/diagnosis , Joint Diseases/diagnosis , Staphylococcal Infections/diagnosis , Anti-Bacterial Agents , Bone Diseases/epidemiology , Drug Therapy, Combination/therapeutic use , Female , Humans , Infant, Newborn , Joint Diseases/epidemiology , Male , Retrospective Studies , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Streptococcal Infections/cerebrospinal fluid , Streptococcal Infections/diagnosis , Streptococcus agalactiaeABSTRACT
A case of isolated central nervous system involvement in Lyme disease is described. A 13 year-old boy developed progressive spastic quadraparesis, chronic lymphocytic meningitis with a low CSF glucose concentration and demyelinating lesions of the white matter on MRI. The diagnosis was proved serologically by high antibody titers against Borrelia burgdorferi (BB) in the serum (1:5, 120) and CSF (1:1,280). There was evidence of specific intrathecal immune response against the BB antigen. The patient was treated with penicillin G and then ceftriaxone. The CSF abnormalities quickly improved but improvement of the neurologic symptoms was gradual and to date still incomplete.
Subject(s)
Encephalomyelitis/complications , Lyme Disease/complications , Meningitis/complications , Adolescent , Ceftriaxone/therapeutic use , Child , Encephalomyelitis/drug therapy , Humans , Lyme Disease/diagnosis , Lyme Disease/drug therapy , Male , Meningitis/drug therapy , Penicillin G/therapeutic useABSTRACT
The diagnostic interest of the search for soluble bacterial antigens, using counter-current immunoelectrophoresis (CIE) has been evaluated in 109 children hospitalized with acute infection. In meningitis, CIE was well correlated with cerebrospinal fluid (CSF) culture and allowed a rapid diagnostic orientation in 82% of meningitis which were confirmed by classical bacteriology (CIE has to be performed using CSF and concentrated urine). False positive results were observed with type B meningococcus, especially on urine samples. In respiratory infections, the search for soluble antigens was of no interest except for focal pneumonitis; in that case, CIE was more frequently positive (35%) than blood culture (28%) and led to a 31% increase of correct diagnosis (CIE must be performed using concentrated urine). Serum and pleural fluid investigations were less sensitive. CIE was not useful in case of upper respiratory or nonfocal broncho-pulmonary infection, due to its very low efficiency.
Subject(s)
Antigens, Bacterial/analysis , Bacterial Infections/immunology , Counterimmunoelectrophoresis , Immunoelectrophoresis , Bacterial Infections/cerebrospinal fluid , Bacterial Infections/urine , Child , Child, Preschool , Humans , Meningitis/immunology , Respiratory Tract Infections/immunologyABSTRACT
One case of Cutis marmorata telangiectatica congenita (CMTC) is reported with cutaneous signs, corporal asymmetry, macrocephaly and cerebral vascular malformation. This syndrome allows to recognize a particular type of CMTC and its relationship with other angiomatosis.
Subject(s)
Arm/abnormalities , Head/abnormalities , Intracranial Arteriovenous Malformations/complications , Leg Length Inequality/congenital , Pigmentation Disorders/congenital , Telangiectasis/congenital , Humans , Hypertrophy/congenital , Infant, Newborn , Leg Length Inequality/pathology , MaleABSTRACT
Four cases of congenital toxoplasmosis with hydranencephaly are reported. The anatomic lesions are the consequence of ischemic necrosis and foetal hydrocephalus. The risk of such lesions is highest during the second trimester of pregnancy. The preventive steps against congenital toxoplasmosis are recalled.
Subject(s)
Anencephaly/etiology , Hydranencephaly/etiology , Toxoplasmosis, Congenital/complications , Female , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Complications, Infectious , Prenatal Diagnosis , Risk Factors , Toxoplasmosis/complications , Toxoplasmosis, Congenital/prevention & controlABSTRACT
Encephalitic illnesses with Epstein-Barr virus (EBV) only represent a small percentage of the causes of viral encephalitis. Clinical symptoms are not specific. Biological standards tests carry few elements of direction, only serologic test of infectious mononucleosis confirms the diagnostic of recent EBV infection. Previous observation shows that the initial study can present similarities with herpes simplex encephalitis, which forces the immediate start of treatment by Acyclovir.