11/130. EEG in assessing hydroxycobalamin therapy in neonatal methylmalonic aciduria with homocystinuria. We performed serial electroencephalograms (EEG) in a newborn with methylmalonic aciduria and homocystinuria to assess the effects of hydroxycobalamin (OHcbl) therapy on the CNS. Diagnosis was made at 22 days of age: she had torpor, failure to thrive and hypotonia of the limbs, and intermittent opisthotonus. The first EEG, performed on the first day of therapy, showed abnormal and immature transients, low voltage and very long flat periods in the discontinuous part of the tracing. These features quickly improved during therapy. After 13 days of OHcbl therapy, the EEG tracing became normal for conceptional age and showed normal sleep phases with only minor anomalies; only mild hypotonia still remained and biochemical parameters normalized. The decrease in blood homocysteine (index of blood detoxification) was statistically correlated to the reduction of the length of flat periods in EEG (p < 0.01). In conclusion, changes in neonatal EEG, particularly the length of interburst periods in the intermittent part of the tracing, appeared to be a reliable index for evaluating drug effectiveness in methylmalonic aciduria and homocystinuria. ( info) |
| Venous and arterial thromboembolism can occur in patients with homocystinuria. Resistance to activated protein c, which is caused by a single point mutation in the gene for factor v, renders an individual at risk for thrombosis. It has been suggested that coexistence of hereditary homocystinuria and factor v Leiden mutation might jointly play a role in the development of thrombosis. We analysed six patients with homocystinuria due to cystathionine beta-synthase deficiency for factor v Leiden and prothrombin G20210A mutations. Only one patient was found to have the factor v Leiden mutation in homozygous form and this patient had suffered from severe thrombosis. One patient was found to be heterozygous with no documented thrombosis. None of the patients had prothrombin G20210A mutation. We stress the necessity for screening for known thrombophilic risk factors in patients with cystathonine beta-synthase deficiency. The coexistence of the factor v Leiden mutation can cause severe thrombotic events in patients with homocystinuria. ( info) |
13/130. homocystinuria with transverse sinus thrombosis. A case of cerebral venous thrombosis caused by undiagnosed homocystinuria is reported. The pitfalls regarding the diagnosis of a potentially medically treatable condition are discussed. Cerebral venous thrombosis in children has a variable type of onset and a multiplicity of causes. This type of pathology, although not frequent, is more common than previously thought. Among the different etiologies, undiagnosed homocystinuria is not routinely considered. We report a case of venous thrombosis of the left transverse cerebral sinus in a girl with drug-resistant partial epilepsy and homocystinuria. This diagnosis was considered and confirmed after the appearance of acute cerebral symptoms caused by venous thrombosis. ( info) |
14/130. CblC/D defect combined with haemodynamically highly relevant VSD. An infant with combined methylmalonic aciduria and homocystinuria (cblC/D defect) presented with significant VSD. She underwent successful cardiac surgery at 53 days. ( info) |
15/130. Ventricular septal defect closure in a neonate with combined methylmalonic aciduria/homocystinuria. Methylmalonic acidemia with associated homocystinuria is a rare inborn error of amino acid metabolism affecting energy supply on the cellular level. Its effects on recovery from surgically induced organ ischemia are largely unknown. We report the successful closure of a nonrestrictive ventricular septal defect by following a normothermic strategy combined with ample metabolic substrate supply. ( info) |
16/130. Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient with cystathionine beta-synthase (CBS) deficiency. cystathionine beta-synthase (CBS) deficiency, the most common form of homocystinuria, is an autosomal recessive inborn error of homocysteine metabolism. Treatment of B6-nonresponsive patients centers on lowering homocysteine and its disulfide derivatives (tHcy) by adherence to a methionine-restricted diet. However, lifelong dietary control is difficult. betaine supplementation is used extensively in CBS-deficient patients to lower plasma tHcy. With betaine therapy, methionine levels increase over baseline, but usually remain below 1,500 micromol/L, and these levels have not been associated with adverse affects. We report a child with B6-nonresponsive CBS deficiency and dietary noncompliance whose methionine levels reached 3,000 micromol/L on betaine, and who subsequently developed massive cerebral edema without evidence of thrombosis. We investigated the etiology by determining methionine and betaine metabolites in our patient, and several possible mechanisms for her unusual response to betaine are discussed. We conclude that the cerebral edema was most likely precipitated by the betaine therapy, although the exact mechanism is uncertain. This case cautions physicians to monitor methionine levels in CBS-deficient patients on betaine and to consider betaine as an adjunct, not an alternative, to dietary control. ( info) |
17/130. Bilateral corneal fibrosis in homocystinuria: case report and transmission electron microscopic findings. PURPOSE: To report the unusual occurrence of bilateral, superficial, corneal fibrosis with pannus formation in a young woman with homocystinuria, and to describe the light and transmission electron microscopic findings of these deposits. methods: Excision of the corneal lesion and amniotic membrane transplantation was performed in both eyes. The excised material was studied using light and transmission electron microscopy. RESULTS: Whitish, elevated, irregular masses with superficial vascularization in the peripheral cornea were noted in both eyes. Histopathologic evaluation of the excised corneal tissue revealed variable epithelial thickness with melanin pigment in the basal layer. A fibrovascular pannus, fibrosis and disruption of the Bowman's layer, and fibrosis of anterior stroma were evident. Transmission electron microscopy revealed numerous empty intracytoplasmic vacuoles in the corneal epithelial cells and intracytoplasmic inclusions containing fibrillogranular material in the cytoplasm of keratocytes. CONCLUSION: We report the unusual association of corneal fibrosis and scarring in a young woman with homocystinuria. The deposits revealed the presence of membrane-bound inclusions containing fibrillogranular material in the corneal epithelium and keratocytes. Although the etiology of these deposits is not clear, the condition improved following excision of these lesions and amniotic membrane transplantation. ( info) |
18/130. General anesthesia for patient with homocystinuria--a case report. homocystinuria is an autosomal recessive disease with multiple systemic disorders. Here we report a 15-year-old lad suffering from homocystinuria who required an ocular surgery including lentectomy and implant of plastic lens, OS and anterior retinal cryotherapy, OD under general anesthesia because of lens subluxation and lattice degeneration. It is the elective ocular procedure most commonly performed for homocystinuric children. Proper precautions should be taken during anesthetic management since this condition inspires some particular anesthetic complications that could be prevented by careful consideration and understanding of its pathophysiology. Providentially our patient stood the operation well and was discharged without subsequent thromboembolism or other complication as an aftermath. ( info) |
19/130. CblE type of homocystinuria due to methionine synthase reductase deficiency: clinical and molecular studies and prenatal diagnosis in two families. The cblE type of homocystinuria is a rare autosomal recessive disorder, which manifests with megaloblastic anaemia and developmental delay in early childhood. This disease is caused by a defect in reductive activation of methionine synthase (MTR). Our study was directed at clinical, biochemical, enzymatic and molecular characterization of two Czech patients with the cblE type of homocystinuria. Case 1 involves a 20-year-old mentally retarded patient who presented with megaloblastic anaemia at 10 weeks of age. She was treated with folates and vitamin B12, and subsequent attempts to cease administration of folates led to recurrence of megaloblastic anaemia. Biochemical features included severe hyperhomocysteinaemia and hypomethioninaemia and in fibroblasts defective formation of methionine from formate, and no complementation with cblE cells. Subsequent molecular analysis of the methionine synthase reductase (MTRR) gene revealed compound heterozygosity for a transition c.1459G>A (G487R) and a 2bp insertion (c.1623-1624insTA). Case 2 involves an 8-year-old girl with nystagmus and developmental delay in whom megaloblastic anaemia was detected at 11 weeks of age. Severe hyperhomocysteinaemia with normal methionine levels was found and enzymatic and complementation studies confirmed the cblE defect. This patient is homozygous for a 140 bp insertion (c.903-904ins140). The insertion is caused by a T>C transition within intron 6 of the MTRR gene, which presumably leads to activation of an exon splicing enhancer. In the families of both patients, enzymatic and mutation analyses were successfully used for prenatal diagnosis. Our study expands the knowledge of the phenotypic and genotypic variability of the cblE type of homocystinuria and supports the concept that this disorder is caused by mutations in the MTRR gene. ( info) |
| homocystinuria usually presents with ectopia lentis, mental retardation, thromboembolic complications, and skeletal abnormalities. Whereas neuropsychiatric abnormalities are often recognized in untreated homocystinuria, initial presentation with acute psychosis has only rarely been reported. We describe a previously well 17-year-old adolescent with an acute psychosis characterized by auditory and visual hallucinations and marked paranoia who was found to have pyridoxine-responsive homocystinuria. His mental state normalized within several weeks of inception of pyridoxine and antipsychotic therapy. pyridoxine-responsive homocystinuria is commonly missed on neonatal screens and should be recognized as a potentially treatable cause of acute psychosis in childhood and adolescence. ( info) |