[Late onset 3-HMG-CoA lyase deficiency: a rare but treatable disorder]. / Déficit en 3-HMG-CoA lyase à révélation tardive : savoir reconnaître une maladie rare mais traitable.

3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder due to a deficiency of the 3-hydroxy-3-methylglutarylCoA lyase (HMG-CoA lyase), a mitochondrial enzyme involved in ketogenesis and in the final step of l-leucine catabolism. HMG-CoA lyase deficiency can lead, in particular circumstances, such as fever, prolonged fasting or digestive disorders, to brutal and severe hypoglycemia with metabolic acidosis and sometimes fatal coma. We report on a new case of 3-hydroxy-3-methylglutaric aciduria particular by its late onset in a 3-year-old patient. Molecular investigation identified two new sequence modifications in the HMGCL gene: c.494G>A (p.Arg165Gln) and c.820G>A (p.Gly274Arg). We remind about this case report that the therapeutical is mainly preventive and allows a very good prognosis for this disease. Long-term treatment consists in limited fasting time, continuous low protein diet and l-carnitine supplementation. Preventive measures are essential: prevention of fasting and emergency treatment during intercurrent infections.

[A cause of intracerebral calcifications that should be known: pseudohypoparathyroidism Ib]. / Une cause de calcifications intracérébrales à connaître: la pseudohypoparathyroïdie de type Ib.

In children, pseudohypoparathyroidism (PHP) is a rare but classical cause of basal ganglia calcifications. It is caused by resistance to parathormone (PTH). Hypocalcemia, which may be symptomatic, is its main feature. We report the case of a 13-year-old boy, affected by type Ib PHP revealed by hypocalcemia and seizures, with basal ganglia calcifications on the CT scan. We describe the characteristics of the 2 main types of PHP and emphasize the search for this disease when basal ganglia calcifications are discovered, even fortuitously, on a cerebral CT scan.

Absence of congenital prethrombotic disorders in children with Legg-Perthes disease.

Resistance to activated protein C (RPCA) and other congenital prethrombotic disorders have been recently reported to be strongly associated with Legg-Perthes disease. RPCA and deficiencies of protein C, protein S, and antithrombin III were sought in 22 children with Legg-Perthes disease. Detection of the factor V Leiden mutation was found in children with RPCA. Twenty-two healthy children paired by age and sex served as controls. The prevalence of congenital prethrombotic disorders was not found to differ significantly among patients with Legg-Perthes disease and among control subjects. Only one patient had RPCA; this patient was heterozygous for the factor V Leiden mutation. Twenty patients and all the control subjects had entirely normal coagulation results. The authors conclude that unless more data become available, RPCA and deficiencies of protein C, protein S, and antithrombin III should not be considered associated with Legg-Perthes disease.

Stüve-Wiedemann syndrome and defects of the mitochondrial respiratory chain.

The Stüve-Wiedemann syndrome (SWS) comprises short stature, congenital bowing of the long bones, respiratory distress, and recurrent episodes of unexplained hyperthermia. The skeletal radiographic changes include short and broad long bones, large metaphyses, internal cortical thickening, and angulation primarily of tibiae and femora, but also of humeri and forearm bones. We report 3 cases of SWS from 2 different unrelated consanguineous gypsy families. All 3 cases fulfilled the clinical and radiological criteria of SWS. Two patients died shortly after birth, whereas the third one was alive at the age of one year. Besides hyperthermic episodes, one patient had hyperaminoaciduria, hepatic failure, and megaloblastic anemia which prompted us to investigate mitochondrial respiratory chain in 2 cases. Abnormal results consisting of decreased activities of complex I and IV were found in both. The simultaneous occurrence of both SWS phenotype and abnormal mitochondrial metabolism in two unrelated cases strongly supports the hypothesis of a pathogenetic relationship between the two events. These cases may also be related to recent reports on the effects of the mitochondrial respiratory chain defects on embryogenesis.

Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionine beta-synthase mutations.

Fasting and post-methionine load plasma total homocysteine concentrations were investigated in the parents of two homocystinuric patients. Three genetic mutations in the cystathionine beta-synthase gene were found. In the patient of family 1, a frequent Caucasian mutation. T833C, was found on one allele, while the mutation on the other allele has not yet been defined. In the patient of family 2, a mutation C569T, recently described by Sperandeo and colleagues, was found on one allele, while a novel mutation, G346A, was characterized on the other allele. The frequent gene mutation T833C was detected in a heterozygous mother who, surprisingly, exhibited strictly normal fasting and post-methionine load homocysteinaemia. In contrast, in the other family, we found a novel mutation (G346A) in the mother located near Lys 119, the putative binding site of phosphopyridoxal phosphate. This mother exhibited increased fasting and post-methionine load homocysteinaemia. These observations could explain the conflicting results reported for vascular pathologies in parents of homocystinuric patients and direct the search for genetic mutations in these vascular pathologies.

Early-onset fatal encephalomyopathy associated with severe mtDNA depletion.

UNLABELLED: We studied a 3-month-old girl who was admitted to hospital because of respiratory distress. The clinical course was characterized by a rapidly progressive generalized hypotonia with lactic acidosis and she died at 4 months of age. A muscle biopsy showed few ragged-red fibres and lack of histochemical cytochrome c oxidase reaction in all fibres. Enzyme activities of the respiratory chain complexes containing subunits encoded by the mitochondrial DNA (mtDNA) were markedly decreased. A quantitative Southern blot analysis revealed 99% depletion of mtDNA in muscle and normal amounts in blood. There was no family history and the dizygotic twin sister of the patient was no symptomatic. CONCLUSION: This new case confirms the rapidly fatal evolution associated with severe depletion of muscle mtDNA.

[Salmonella aortitis complicated by rupture. Diagnostic and therapeutic problems]. / Aortite à salmonelles, compliquée de rupture. Problèmes diagnostiques et thérapeutiques.

We observed a case of aortitis due to Salmonella in a patient with spondylodiscitis. Outcome was fatal despite resection and grafting, extensive drainage and adapted but unsuccessful antibiotic treatment. Based on the literature, suggested treatment for patients with spondylodiscitis includes extra-anatomic bypass combined with resection of the infected tissue and adapted antibiotherapy. In these emergency cases, computed tomography is the most useful exploration and also gives the diagnosis of spondylodiscitis. It is also necessary to identify the infectious agent to adapt the antibiotics.

[Disseminated osseous angiomatosis in children]. / Les angiomatoses osseuses disséminées de l'enfant.

The authors review 54 cases of diffuse bone angiomatosis (one new case and 53 from the literature) and describe the major clinical, radiological and anatomical features. The difficulties of distinguishing between haemagiomata and lymphangiomata are emphasised. The diagnosis is often helped by the presence of visceral or cutaneous lesions and when such lesions are found, a skeletal survey should always be done. These conditions, which may be classified under the general heading of angiodysplasias of bone, are hamartomata and must be distinguished from other bone lesions of vascular origin.

Effects of glycerol on human adipose tissue triglyceride lipase activity.

Glycerol fully protects the human adipose tissue triglyceride lipase against the denaturing effects of high and low temperatures. Under such protection, storage of crude preparations at -10 degrees C or incubation at 50 degrees C resulted in a 1.5-3-fold increase of the measured lipase activity. This increase was shown to be related to enzyme newly released from tissular microparticles present in the samples. Advantage may be taken of these observations to improve greatly the conditions of extraction and storage of this lipase activity.