Spastic gait, intellectual disability and seizures due to a rare mutation causing hyperargininemia.

Hyperargininemia is an autosomal recessive disorder caused by a defect in the arginase I enzyme. We present a case of a 20-year-old male with severe spastic gait, intellectual disability and seizures. Metabolic tests revealed high levels of arginine in blood serum. Hyperargininemia was attributed to a likely pathogenic rare mutation of ARG1 gene [Chr6: g131905002_131905002 G>A (p.Arg308Gln) homozygous] detected in Whole Exome Sequencing resulting in deficiency in arginase I enzyme. Following the diagnosis, the patient has been treated with low protein diet, aminoacid and vitamin supplements. The accumulation of arginine, may contribute to the pathogenesis of severe neurological manifestations, however, low protein intake diet may lead to a favorable outcome. Therefore, clinicians should screen for hyperargininemia in early childhood in case of strong clinical suspicion.

[Peripheral neuropathy with hypervitaminosis B6 caused by self-medication]. / Neuropathie périphérique avec hypervitaminose B6 provoquée par l'automédication.

INTRODUCTION: Vitamin B6 is contained in a number of over-the-counter drugs and vitamin supplements. It may cause severe neurological troubles in case of overdosage. CASE REPORT: We report the case of a 92-year-old women with gait disorders. A diagnosis of peripheral neuropathy with both motor and sensitive deficits was established and investigated. Blood level of vitamin B6 was measured to investigate a potential deficiency. Unexpectedly, the results showed hypervitaminosis B6, which appears to be due to self-administration of an over-the-counter drug containing vitamin B6. Discontinuation of this drug was associated with decrease in vitamin B6 level as well as gait improvement. We also discuss the toxicity of vitamin B6. CONCLUSION: Hypervitaminosis B6 remains a possible cause of peripheral neuropathy and it may be caused by self-administration of over-the-counter vitamin-containing drugs.

Gait instability in valproate-treated patients: Call to measure ammonia levels.

OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 µmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three. CONCLUSIONS: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Effects of manganese from a commercial multi-trace element supplement in a population sample of Canadian patients on long-term parenteral nutrition.

BACKGROUND: Long-term parenteral nutrition (PN) can be associated with micronutrient deficiency or toxicity depending on supplementation. Recently, hypermanganesemia and potential neurological toxicity were reported. The aim of this study was to assess the effect of manganese supplementation in a sample of patients on long-term PN receiving manganese (Mn) as part of a multi-trace element (TE) supplement. METHODS: A convenience sample of 16 patients underwent clinical and blood biochemical measurements as well as magnetic resonance imaging (MRI) of the brain. Descriptive statistics were performed. RESULTS: The mean daily Mn supplementation was 7.28 ± 0.97 µmol/d (400 ± 53 µg/d), which was within the American Medical Association Nutrition Advisory Group guidelines of 2.73-14.56 µmol/d (150-800 µg/d) but exceeded the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) 2002 recommendations of 1.09-1.82 µmol/d (60-100 µg/d). The mean whole blood Mn level was 1.38 ± 0.29 times the upper limit of normal (ULN), and 8 of 14 patients with blood measurements had Mn levels above ULN. On MRI, 81% of patients had high signals on T1-weighted images assumed to be Mn deposits in their basal ganglia. Two patients with positive MRI (15%) had a clinical diagnosis of Parkinson disease. Multiple neuropsychiatric complaints were reported, including depression (66%), lack of concentration (42%), memory disturbances (17%), and gait instability (8%). CONCLUSION: These results suggest that Mn status is elevated in these patients. Manganese supplementation should be used with caution in patients receiving long-term PN, and attention should be paid to the Mn content of multi-TE supplements.