Biomedical subjects

Thierry Billette de Villemeur

Publications and source records attributed to Thierry Billette de Villemeur.

8 recordsLinked to original sources

PubMed2006

Herpes simplex virus encephalitis in human UNC-93B deficiency.

Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-alpha/beta and -lambda antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity.

Child, Preschool↗

PubMed2006

Long-term follow-up and adult outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency.

Little information is available on the long-term course and adult outcome of patients with 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. We describe the course of a 32-year-old woman with hypotonia, dystonia, choreoathetosis, mental retardation, behavioral disturbances, and incomplete puberty due to PTPS deficiency. From the age of 6 months she developed progressive hypotonia and choreoathtetoid movements despite good control of hyperphenylalaninemia. Tetrahydrobiopterin deficiency was diagnosed at age 3 years. She had a dramatic response to L-dopa, which persisted at a stable dose for 29 years. Reducing the L-dopa dose led to severe axial hypotonia and limb dystonia, and increasing it led to florid abnormal movements and behavioral disorders. This report illustrates the role of dopamine modulation in motor, psychiatric, and endocrine functions.

Adolescent↗

PubMed2005

Dystonia and parkinsonism in GM1 type 3 gangliosidosis.

GM1 gangliosidosis is due to beta-galactosidase deficiency. Only patients with type 3 disease survive into adulthood and develop movement disorders. Clinical descriptions of this form are rare, particularly in non-Japanese patients. We describe four new patients and systematically analyze all previous reports found by a literature search and contacts with the authors for additional information. Generalized dystonia remained the predominant feature throughout the disease course and was often associated with akinetic-rigid parkinsonism. GM1 gangliosidosis must be considered as a cause of early-onset generalized dystonia, particularly in patients with short stature and skeletal dysplasia.

Adolescent↗

PubMed2004

Myoclonus and generalized digestive dysmotility in triple A syndrome with AAAS gene mutation.

We report on the case of a 25-year-old woman with triple A syndrome and gene mutation, who, during the long follow-up period of 23 years, developed myoclonus of the face and the upper limbs (with normal brain magnetic resonance spectroscopy) and widespread digestive dysmotility, involving small bowels and gall bladder. These features, not previously described, illustrate an extension of the cerebral and digestive neurological involvement in this syndrome.

Adrenal Gland Diseases↗

PubMed2004

The deleterious G15498A mutation in mitochondrial DNA-encoded cytochrome b may remain clinically silent in homoplasmic carriers.

We report on a patient with severe growth retardation and IgF1 deficiency, in which a mitochondrial abnormality was suspected. An isolated mitochondrial respiratory chain complex III deficiency was found in blood lymphocytes and skin fibroblasts. Sequence analysis of the cytochrome b, which is the only mitochondrial DNA-encoded subunit of complex III, revealed a homoplasmic G15498A mutation, resulting in the substitution of a highly conserved amino acid (glycine 251 into an aspartic acid). The mutation was found to be homoplasmic in all tissues examined from the mother and her brother (lymphocytes, fibroblasts, hair roots and buccal cells). Complex III deficiency was also demonstrated in these cells. Nevertheless, the mother and the brother were asymptomatic. This mutation had been considered as a cardiomyopathy-generating mutation in a previously reported case, and its pathogenicity has been demonstrated recently in yeast. However, it seems not to fulfil the classical criteria for pathogenicity of a mitochondrial DNA mutation, especially the heteroplasmic status, and to be clinically silent, albeit present, in nonaffected relatives. We suggest that other factors are contributing to the clinical variability expression of the G15498A mtDNA mutation.

Amino Acid Sequence↗

PubMed2002

Simple fluorescent PCR assay for discriminating FRAXA fully mutated females from normal homozygotes.

Fragile X syndrome linked to the FRAXA locus is the most common inherited genetic disease accounting for mental retardation and is usually caused by the expansion of an unstable CGG repeat in the first exon of the FMR1 gene on the X chromosome. Despite its robustness, Southern blot is not suitable for large-scale routine screening as part of neuropediatric practice. PCR appears as an interesting alternative, and various protocols have been successfully applied to molecular screening in mentally retarded boys and girls. Unfortunately, as of this date these protocols are unable to detect the expanded allele in FRAXA females reliably, thereby failing to discriminate between fully mutated females from normal homozygotes. Therefore, we opted for an alternative approach in designing a semiquantitative PCR assay, based on the amplification of the sole wild-type allele. This method allowed us to detect the presence of one or two normal alleles with the same sizes, thereby discriminating between a FRAXA fully mutated female or a normal homozygote, respectively. A trial on 95 DNA samples from normal and mutated females demonstrated the reliability of the procedure. We believe this simple PCR assay is a powerful approach that would reduce the recourse to Southern blotting in females with mental retardation of unknown etiology.

Base Sequence↗

PubMed2002

[Gaucher's disease ].

Gaucher disease is an uncommon autosomic recessive disorder. The disease is caused by a deficiency in the activity of the lysosomal enzyme glucocerebrosidase which is responsible for the degradation of glucosylceramide, résulting from the breakdown of red and white cell-membranes. In the absence of enzyme glucosylceramide accumulates in the lysosomes of macrophages. This accumulation leads to hepatomegaly, splenomegaly with subsequent haematologic abnormalities (leucopenia, anemia, thrombopenia) and bone manifestations. Three types of Gaucher disease are described: type 1 is the most common, type 2 and 3 are associated with neurologic symptoms. Macrophages are the likely cellular source of biochemical abnormalities: elevated blood level of ferritin, angiotensin converting enzyme, immunoglobulins and haemostasis abnormalities. Lysosomal perturbations lead to increased blood level of tartrate resistant acid phosphatase and chitotriosidase. Enzyme replacement therapy is available in France since 1991. In 2002, 136 patients are treated. The efficacy is overt on the asthenia, organomegaly and haematological manifestations. Bone pains disappear or decrease in intensity, however bone complications may be irreversible justifying treatment initiations before the appearance of lesions that may lead to serious functional impairment.

Biomarkers↗

PubMed2002

[French results of enzyme replacement therapy in Gaucher's disease].

Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia. Patients with Gaucher disease have been classified in three types: type I is the more common, neurological manifestations occur in types II and III. Enzyme replacement therapy (ERT) with modified placental human glucocerebrosidase (ceredase) or recombinant glucocerebrosidase (cerezyme) is effective in most type I Gaucher disease and has become the current standard care administered to thousand of patients worldwide. ERT has obviated the need for bone marrow transplantation and virtually eliminated the need for splenectomy. We report here the French study including adults and children. ERT of 30 to 60 U/K every two weeks as starting dose was administrated to 108 patients with severe type I Gaucher disease. ERT fully reverse many of the manifestations of the disease. ERT regimen alleviated fatigue, and hematological and visceral signs and symptoms in nearly all severely-ill patients. Skeletal responses to treatment develop much more slowly than hematological or visceral responses. Studies in pediatrics show that the disease is more severe in children. These children should be treated early in the course of their disease to avoid irreparable damage. Hematological manifestation in type II cannot be reversed with enzyme replacement. In type III treatment can rarely reverse neurological deficit. Gaucher disease is also an excellent candidate for gene therapy.

Adult↗