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Biomedical subjects

A B Burlina

Publications and source records attributed to A B Burlina.

At least 19 recordsLinked to original sources
PubMed2007

Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I).

Glutaryl-CoA dehydrogenase (GCDH) deficiency is an autosomal recessive disease with an estimated overall prevalence of 1 in 100 000 newborns. Biochemically, the disease is characterized by accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas chromatography-mass spectrometry of organic acids or tandem mass spectrometry of acylcarnitines. Clinically, the disease course is usually determined by acute encephalopathic crises precipitated by infectious diseases, immunizations, and surgery during infancy or childhood. The characteristic neurological sequel is acute striatal injury and, subsequently, dystonia. During the last three decades attempts have been made to establish and optimize therapy for GCDH deficiency. Maintenance treatment consisting of a diet combined with oral supplementation of L: -carnitine, and an intensified emergency treatment during acute episodes of intercurrent illness have been applied to the majority of patients. This treatment strategy has significantly reduced the frequency of acute encephalopathic crises in early-diagnosed patients. Therefore, GCDH deficiency is now considered to be a treatable condition. However, significant differences exist in the diagnostic procedure and management of affected patients so that there is a wide variation of the outcome, in particular of pre-symptomatically diagnosed patients. At this time of rapid expansion of neonatal screening for GCDH deficiency, the major aim of this guideline is to re-assess the common practice and to formulate recommendations for diagnosis and management of GCDH deficiency based on the best available evidence.

Child↗
PubMed2006

An unusual clinical and biochemical presentation of ornithine transcarbamylase deficiency in a male patient.

We report a male patient with a history of recurrent idiopathic vomiting, normal plasma ammonia and glutamine concentrations in acute phase, who died at 3 years of age. Ornithine transcarbamylase deficiency was diagnosed after detecting elevated urinary orotate concentrations in a sample collected just before death, and the diagnosis was confirmed by DNA analysis.

Amino Acid Metabolism, Inborn Errors↗
PubMed2005

Genetic analysis carried out on blood-spots of phenylalanine hydroxylase-deficient newborns detected by northeastern Italian neonatal screening.

The aim of this work was to perform genetic analysis on 18 different blood-spot samples collected from neonates detected as hyperphenylalaninemic by Northeastern Italian screening program. DNA was extracted from blood-spots. Exons/introns of PAH gene were amplified by polymerase chain reaction (PCR), and PCR products were purified and sequenced with both forward and reverse primers. The most frequent mutations were IVS12nt1g>a (16.7%) and R408W, P281L and L48S (all together 11.1%). As expected, compound heterozygosity was the usual finding; homozygosity was found only in two patients with R158Q and IVS2nt5g>c mutations. The V230I mutation was reported for the first time in Italy. We found six previously described polymorphisms (V245V, IVS4nt47c>t, IVS2nt19t>c, IVS3nt-22c>t, IVS5nt-54a>g, and E280>Q280). To our knowledge, four genotypes were not previously described: R158Q/V230I present in one patient with classical PKU; and L48S/R408Q, A403V/IVS2nt-13t>g, and G272X/V230I present in patients showing HPA phenotype. Most of the mutations were located in the exons 12 and 7 and in exon/intron 2 (83.3% detection of total mutations in PKU or HPA patients of Northeastern Italy). From a practical viewpoint, the genetic analysis of blood-spots collected on Guthrie cards for neonatal screening for PKU could be a simple method to establish the genotype of neonates. Consequently, the genotype/phenotype correlation could lead to a more accurate diagnosis and prognosis for families.

Amino Acid Substitution↗
PubMed2005

Efficacy of ACE-inhibitor therapy on renal disease in glycogen storage disease type 1: a multicentre retrospective study.

BACKGROUND: The efficacy of ACE-inhibitors in decreasing microalbuminuria and proteinuria has been reported in a few patients with glycogen storage disease type 1 (GSD1); however, no case-control study has ever been published. AIM: The aim of the current study was to evaluate the efficacy of ACE-inhibitors in reducing glomerular hyperfiltration, microalbuminuria and proteinuria, and in delaying the progression of renal damage. PATIENTS AND METHODS: Ninety-five patients (median age at the time of the study: 14.5 years) were enrolled from nine Italian referral centres for metabolic diseases. A retrospective study of a 10-year follow-up was conducted in order to compare the evolution of these parameters in treated patients with those who were not treated with ACE-inhibitors. RESULTS: A significant and progressive decrease of glomerular filtration rate was observed in treated patients vs. those who were not treated with ACE-inhibitors (P < 0.05). No difference was observed for microalbuminuria and proteinuria between the two groups of patients. Moreover, the ACE-inhibitors significantly delayed the progression from glomerular hyperfiltration to microalbuminuria, but not that from microalbuminuria to proteinuria. CONCLUSIONS: The results of the present study underline the importance of a strict follow-up of renal function in GSD1 patients. The detection of glomerular hyperfiltration suggests precocious initiation of ACE-inhibitor treatment to delay the progression of renal damage. A randomized prospective study is needed to establish for certain the real effectiveness of this treatment in GSD1 patients.

Adolescent↗
PubMed2004

Hypertelorism, ptosis, and myopia associated with drug-resistant epilepsy, mental delay, growth deficiency, ectodermal defects, and osteopenia.

We report a 30-year-old woman with hypertelorism, ptosis, and myopia associated with drug-resistant epilepsy (DRE, Lennox-Gastaut syndrome), mental delay, growth deficiency, ectodermal defects, and osteopenia. To the best of our knowledge, this patient has an unusual combination of symptoms not previously described, associated with severe central nervous system dysfunction. The ectodermal defects were present in a very intriguing form, were difficult to diagnose, and did not conform to any classification or previous description.

Adult↗
PubMed2004

Hepatocyte transplantation for inborn errors of metabolism.

Liver transplantation for inborn errors of metabolism has proved effective in some (mostly liver-associated) inborn errors of metabolism. Significant morbidity and mortality rates have been extensively reported due to disease recurrence or to complications of the immunosuppressive regimen. On the basis of clinical trials in animals as well as in humans, the use of isolated hepatocytes offers a unique opportunity for treating inborn errors of metabolism. The state of art of the technique applied to this field is reviewed here and related practical problems are examined. No final conclusions can be drawn, but further insight into the use of alternative sources of cells, including stem/progenitor cells associated with cryobiology and immunological research, will offer new opportunities for cell therapy for inborn errors of metabolism in the near future.

Animals↗
PubMed2004

Management of movement disorders in glutaryl-CoA dehydrogenase deficiency: anticholinergic drugs and botulinum toxin as additional therapeutic options.

Glutaric aciduria type I is an inborn error of metabolism due to the deficiency of glutaryl-CoA dehydrogenase, an enzyme responsible for the catabolism of lysine, hydroxylysine and tryptophan. The most important neurological symptoms include dyskinesia and dystonia, which can be focal, segmental or generalized. Treatment of the extrapyramidal syndrome is often unsatisfactory. We report our experience in the treatment of generalized and focal dystonia with anticholinergic drugs and botulinum toxin type A, respectively. Both therapies proved beneficial.

Adolescent↗
PubMed2004

Follow-up of a child with hypoacetylaspartia.

We provide a 5-year follow-up of a patient previously reported to have no NAA signal on neurospectroscopy. At 8 years this boy was found to have profound neurological dysfunction: he had truncal ataxia, no expressive speech, behaviour abnormalities, secondary microcephaly and cognitive achievements corresponding to less than 12 months of age. He started to have generalized seizures at 5 years 9 months. Although not directly proven we assume an inborn error of NAA metabolism, possibly a defect of the anabolic enzyme L-aspartate N-acetyltransferase (EC 2.3.1.17).

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Diffusion-weighted imaging in the assessment of neurological damage in patients with methylmalonic aciduria.

Diffusion-weighted magnetic resonance imaging (DW-MRI) of the brain was performed in two patients with methylmalonic aciduria who presented signs and symptoms of neurological involvement without metabolic decompensation. Patient 1 presented acute metabolic stroke and patient 2 presented subacute encephalopathy. Brain DW-MRI confirmed very recent damage in patient 1, while the absence of brain lesions on brain DW-MRI indicates the development of more chronic damage in patient 2. Brain DW-MRI represents an additional and complementary tool in the assessment of brain damage in methylmalonic aciduria patients who develop neurological syndrome.

Adolescent↗
PubMed2002

Diffusion-weighted MRI of maple syrup urine disease encephalopathy.

We report the case of a newborn child with maple syrup urine disease (MSUD), diagnosed at 10 days of life. Diffusion-weighted echoplanar MRI showed marked hyperintensity of the cerebellar white matter, the brainstem, the cerebral peduncles, the thalami, the dorsal limb of the internal capsule and the centrum semiovale, while conventional dual-echo sequence evidenced only a weak diffuse T2 hyperintensity in the cerebellar white matter and in the dorsal brainstem. The apparent diffusion coefficient (ADC) of these regions was markedly (>80%) decreased. Therefore, in agreement with current hypotheses on MSUD pathogenesis, MSUD oedema proves to be a cytotoxic oedema. Diffusion-weighted MRI may be a valuable tool, more sensitive than conventional spin-echo techniques, to assess the extent and progression of cytotoxicity in MSUD, as well as the effectiveness of the therapeutic interventions.

Diffusion↗
PubMed2001

Treatable neurotransmitter deficiency in mild phenylketonuria.

The authors describe a case of neurologic involvement in mild hyperphenylalaninemia (HPA), not due to tetrahydrobiopterin (BH(4)) deficiency, with low levels of monoamine neurotransmitter metabolites in CSF. The combined BH(4)-Phe loading test suggested a BH(4) response, confirmed by clinical improvement after BH(4) therapy. Molecular study revealed a compound heterozygosity of the phenylalanine hydroxylase alleles: a mild HPA-associated mutation (T380M) and the new mutation D151E. This case demonstrates that even mild HPA, generally considered a benign disorder, may present neurologic impairment.

Adolescent↗
PubMed2001

Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

The authors report the clinical and molecular findings in eight patients with hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome. The most consistent neurologic finding was spastic paraparesis, seen in five of the eight patients. However, all showed signs of pyramidal tract involvement. A broad spectrum of pathogenetic mutations (including missense, nonsense, splice site, insertion, and deletions) were identified in the ORNT1 gene.

Adolescent↗
PubMed2001

Long-term treatment with sodium phenylbutyrate in ornithine transcarbamylase-deficient patients.

Ornithine transcarbamylase deficiency is a very heterogeneous urea cycle disorder resulting in hyperammonemia with various presentations from the neonatal period through adulthood. We performed a retrospective study in nine patients (four male/five female, age at diagnosis ranging from 6 days to 14 years) to evaluate the safety and efficacy of sodium phenylbutyrate (Ammonaps) in long-term treatment. All patients were diagnosed by DNA mutational analysis and/or liver enzyme measurement. They had previously been treated with sodium benzoate (median dose 248 mg/kg/day; range 106-275) and low protein diet (median 0.84 g/kg/day) and were switched to sodium phenylbutyrate (median dose of 352 mg/kg/day) at 8.9 and 4.9 years of age (median) in males and females, respectively. We analyzed clinical and biochemical data and the median follow-up duration was 26 months. During that time, there were no hyperammonemic episodes requiring hospitalization. Median plasma ammonia and glutamine levels were 30 and 902 micromol/L, respectively. Total protein intake could be increased to 0.95 g/kg/day after 18 months. No side effects related to therapy were observed. Further prospective studies should be performed to define the optimal dosage of sodium phenylbutyrate and the requirements for protein diet at different ages.

Adolescent↗
PubMed2000

Evaluation of urinary acylglycines by electrospray tandem mass spectrometry in mitochondrial energy metabolism defects and organic acidurias.

We analyzed the urinary acylglycine excretion in 26 patients with mitochondrial energy metabolism disorders and in 55 patients with organic acidurias by electrospray tandem mass spectrometry (ESI-MS/MS), monitoring precursor ions of m/z 90. Urinary concentrations of the different acylglycines were quantified using deuterated internal standards. Normal values for the most important acylglycines were established. In MCAD and MAD (neonatal form) deficiencies, typical excretion patterns of urinary acylglycines were found in all the samples. In isovaleric aciduria, propionic aciduria, and 3-methylcrotonylglycinuria typical glycine conjugates were always found. Methylmalonic aciduria (mutase deficiency), multiple carboxylase deficiency, and 3-hydroxy-3-methylglutaric aciduria revealed pathological acylglycine profiles, even if not specific for the disease. In all these diseases acylglycine excretion seems to be less influenced by the clinical status than organic acid excretion. This method is a useful diagnostic tool for these metabolic disorders, complementary to organic acids and acylcarnitine profiles.

Acyl-CoA Dehydrogenase↗