Anterior Spinal Artery Syndrome Due to Fibrocartilaginous Embolism-Case Report and Treatment Options.

Acute occlusion of the anterior spinal artery and subsequent spinal ischemic infarction leads to anterior spinal artery syndrome characterized by back pain and bilateral flaccid paresis with loss of protopathic sensibility. As a rare cause fibrocartilaginous embolism has been described and is associated with sports or unusual strain.Following gymnastic exercise the day before symptom-onset, a 11 years old girl presented with neck pain, paresis of arms and legs, and impaired deep tendon reflexes. She was unable to lift her arms, grasp, stand, walk and had urinary incontinence. Magnetic resonance imaging revealed a longitudinal T2 hyperintense signal in the anterior spinal cord from C3 to C6 with accompanying bilateral diffusion restriction involving gray matter bilaterally at the level of C4 and C5 and unilaterally at the level of C3/4. The adjacent annulus fibrosus of the intervertebral disc showed a fissure without disc protrusion. Treatment with prednisolone and enoxaparin was started within 12 hours of symptom-onset and continued over 6 days and 8 weeks, respectively. After 2 months, her motor function gradually improved, spinal imaging showed persistent T2 signal hyperintense defects at the level of C4/5. After 5 months, there was only slight impairment affecting elevation and abduction of the right arm.Following physical exercise, the patient suffered from acute anterior spinal cord ischemia with imaging findings in line with a presumed fibrocartilaginous embolism. Unlike most cases, our patient showed almost complete recovery following treatment with prednisolone and enoxaparin. We speculate that the positive outcome is related to rapid treatment initiation.

Dietary habits and metabolic control in adolescents and young adults with phenylketonuria: self-imposed protein restriction may be harmful.

BACKGROUND: In untreated patients, phenylketonuria (PKU) results in severe encephalopathy with mental retardation. A protein-restricted diet is recommended which can be relaxed in adolescence/adulthood. METHODS: We contacted all 72 adult/adolescent PKU patients who had been treated in our center during early childhood. Some still regularly attended our outpatient clinics, while others were lost for follow-up, giving 51 patients in our study. We asked all patients to complete a dietary protocol as well as a questionnaire on quality of life. Blood and urine were analyzed and body impedance plethysmography and cerebral MRI were performed. RESULTS: 42 % of the patients followed protein restriction supplemented with amino acid mixtures (AAM), others had a vegan diet with (8 %) or without (14 %) AAM; 36 % said they were eating normally and did not need any AAM. However, based on dietary protocols and blood urea levels, protein intake was restricted in this patient group. None of the patients examined had serious nutritional deficits. Phenylalanine levels were higher in patients not taking AAM. MRI of the brain was not different from those following protein restriction and taking AAM. The lesions score and mood correlated best with the cumulative phenylalanine values during the first 10 years of life. CONCLUSION: In summary, 50 % of adult/adolescent patients from our center did not take AAM at the start of our survey although they unknowingly followed self-imposed protein restriction. They had no overt nutritional deficits; however, long-term brain function may be compromised. Our study emphasizes the need for specialized metabolic care in PKU during adulthood.

3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy.

OBJECTIVE: 3-Methylglutaconic aciduria type I is a rare inborn error of leucine catabolism. It is thought to present in childhood with nonspecific symptoms; it was even speculated to be a nondisease. The natural course of disease is unknown. METHODS: This is a study on 10 patients with 3-methylglutaconic aciduria type I. We present the clinical, neuroradiologic, biochemical, and genetic details on 2 new adult-onset patients and follow-up data on 2 patients from the literature. RESULTS: Two unrelated patients with the characteristic biochemical findings of 3- methylglutaconic aciduria type I presented in adulthood with progressive ataxia. One patient additionally had optic atrophy, the other spasticity and dementia. Three novel mutations were found in conserved regions of the AUH gene. In both patients, MRI revealed extensive white matter disease. Follow-up MRI in a 10-year-old boy, who presented earlier with isolated febrile seizures, showed mild abnormalities in deep white matter. CONCLUSION: We define 3-methylglutaconic aciduria type I as an inborn error of metabolism with slowly progressive leukoencephalopathy clinically presenting in adulthood. In contrast to the nonspecific findings in pediatric cases, the clinical and neuroradiologic pattern in adult patients is highly characteristic. White matter abnormalities may already develop in the first decades of life. The variable features found in affected children may be coincidental. Long-term follow-up in children is essential to learn more about the natural course of this presumably slowly progressive disease. Dietary treatment with leucine restriction may be considered.

Scheie syndrome: enzyme replacement therapy does not prevent progression of cervical myelopathy due to spinal cord compression.

Hurler-Scheie syndrome is caused by alpha-l-iduronidase deficiency. Enzyme replacement therapy (ERT) can improve physical capacity and reduces organomegaly. However, the effect on bradytrophic connective tissue is limited. As intravenously administered enzyme cannot cross the blood-brain barrier, the therapy of choice for the more severe Hurler syndrome is haematopoietic stem cell transplantation (HCT). In the more attenuated Scheie syndrome, neurological impairment is less severe; therefore, ERT may be appropriate to treat these patients. Information on long-term outcome in Scheie patients undergoing ERT is scarce. We report a 38-year-old female Scheie patient who has been on ERT for 8 years. While non-neurological symptoms improved, she developed paresthesias in her hands and feet and progressive pain in her legs. Somatosensory evoked potentials were abnormal, suggesting dysfunction of the dorsal funiculus and lemniscus medialis. After 6 years of ERT, a spinal MRI showed dural thickening at the upper cervical spine. These soft-tissue deposits are presumably due to the accumulation of mucopolysaccharides. Intramedullary hyperintensities at the level of C1/2 revealed cervical myelopathy. An MRI before the start of ERT had shown milder spinal lesions. Cystic lesions in the white matter of the centrum semiovale due to dilated Virchow-Robin spaces were essentially unchanged compared with the MRI scan before ERT. Decompression of the spinal cord resulted in clinical improvement. In an adult patient with Scheie syndrome, ERT failed to prevent progression of cervical myelopathy. Clinical significance of cerebral changes is unclear. Whether early HCT or intrathecal ERT could have prevented these lesions remains speculative.

Prenatal benzoate treatment in urea cycle defects.

OBJECTIVE: In patients with severe urea cycle defects (UCD) metabolic decompensation with hyperammonaemia typically occurs during the first days of life resulting in severe neurological damage or death. Benzoate can eliminate nitrogen independent of the urea cycle. Usually, benzoate is started soon after birth, but prenatal administration might improve metabolic stability. DESIGN: Two fetuses with a prenatal diagnosis of UCD (female: citrullinaemia; male: ornithine transcarbamylase deficiency) were loaded with benzoate prenatally via the placenta by infusing their mothers with benzoate. Benzoate concentrations were measured in umbilical cord blood and the blood of the mothers and their newborns. RESULTS: Therapeutic concentrations of benzoate were found in umbilical cord blood and in the children's blood. Thus, benzoate transfer across the placenta was demonstrated. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. CONCLUSIONS: Benzoate infusion of the mother shortly before birth is safe and results in therapeutic levels of benzoate in umbilical cord blood.

Developmental changes of oxalate excretion in enterally fed preterm infants.

To further substantiate gestational age-related changes in oxalate excretion, we studied urinary oxalate excretion in 66 preterm infants born at 23.4-34.7 weeks of gestation. Spot urine of 66 preterm infants was analysed by ion chromatography as soon as they were completely orally fed with enriched breast milk and/or special preterm milk formula (days 7 to 57 of postnatal life). Infants with evidence of renal, gastrointestinal, muscular or metabolic disease were not included. Newborns on parenteral nutrition were excluded. Oxalate/creatinine ratios (Ox/Cr) decreased with gestational age (three age groups: group 1, 23 0/7-28 0/7; group 2, 28 1/7-32 0/7; and group 3, 32 1/7-35 0/7 weeks of gestation). The mean Ox/Cr was highest in group 1 (398.2 mmol/mol +/- 116.8; n = 21). Differences between groups 1 + 3 were statistically significant; p = 0.001; those between groups 1 + 2 and between groups 2 + 3 were not. Ox/Cr correlated inversely with gestational and maturational age (r = -0.41, p = 0.001; r = -0.33, p = 0.007) and positively with postnatal age (r = 0.32, p = 0.008). It correlated inversely with birth weight as well as actual weight at sample collection (r = -0.46 and -0.44, p < 0.001). Ox/Cr was significantly linked to energy and carbohydrate intake (r = 0.3 and 0.4, p = 0.03 and 0.001). These results were independent of sex. In the present study we show that urinary oxalate excretion in preterm infants depends on gestational age.

Branched chain amino acids as a parameter for catabolism in treated phenylketonuria.

This study was performed to study an association between nutritional status on one hand and BCAA- and Phe-concentrations on the other hand in PKU patients free of infection. AA profiles from 70 PKU patients were measured. 9 patients (subgroup I) with elevated Phe- and BCAA-concentrations as well as 23 patients (subgroup II) with only elevated Phe-levels were included. Dietary records were obtained from both groups; low caloric intake in subgroup I was increased with Duocal or p-am ANAMIX without modifying total protein- and Phe-intake. AA profiles were controlled after 2 weeks. Additionally, we investigated AA profiles from 26 liver transplanted patients with increased carbohydrate and caloric intake as an example for anabolism. In subgroup I Phe- and Isoleu-concentrations decreased sign. After dietary intervention. Leu, Val and Tyr levels decreased not sign. Initial Phe-levels correlated negatively with protein and caloric intake. BCAA concentrations of liver transplanted patients receiving high amounts of carbohydrates were in the lower range of normal. Increased caloric intake lowered most of the elevated Phe- and BCAA- concentrations.