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ABSTRACT: We report on a favourable pregnancy in a woman affected by mut- methylmalonic acidaemia. Under vitamin B12 and carnitine therapy she remained symptom-free throughout pregnancy, labour, delivery and the postpartum period and gave birth to a term, healthy female newborn. At follow-up, the child shows normal somatic and neurocognitive development.
Journal of Inherited Metabolic Disease 06/2002; 25(2):133-4. · 3.58 Impact Factor
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ABSTRACT: We investigated the prognostic indicators in ten hyperammonemic neonates: four treated by continuous arteriovenous hemodialysis (CAVHD), four with continuous venovenous hemodialysis (CVVHD), and two with hemodialysis (HD). Plasma ammonium levels decreased significantly within the first 24 h irrespective of dialysis modality (from 1419 to 114 micromol/l, median values; P<0.0001). CVVHD achieved the highest ammonium clearance. HD provided highest ammonium extraction but clearance was hampered by severe hemodynamic instability. Five patients had a good outcome (normal at follow-up of 9-59 months), five had poor outcome (four died and one has severe neurological damage). Total coma duration was shorter in patients who had a good outcome (47+/-11 vs 78+/-13 h; P=0.02). Remarkably, only coma duration before dialysis determined this difference (22.2+/-10.1 vs 48.8+/-11.2 h; P=0.02). In cases with good outcome, coma duration was <33 h, whereas the others exceeded this limit. The prognosis was not related to dialysis modality, rapidity in reducing ammonium levels or to the underlying metabolic defect. In conclusion, results showed CVVHD to be the optimal modality for extracorporeal ammonium detoxification. However, the most relevant indicator for prognosis was coma duration before the start of dialysis. Therefore, major efforts should be made to refer patients quickly to highly specialized centers.
Pediatric Nephrology 11/2001; 16(11):862-7. · 2.52 Impact Factor
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Journal of Inherited Metabolic Disease 07/2000; 23(4):349-51. · 3.58 Impact Factor
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Clinica Chimica Acta 01/2000; 291(1):97-102. · 2.54 Impact Factor
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ABSTRACT: In addition to systemic manifestations with skeletal, pulmonary, renal, and haematological signs, lysinuric protein intolerance (LPI), a membrane transport defect of cationic amino acids, is often complicated by severe life-threatening immunological manifestations. A 10-year-old boy with LPI who exhibited a severe systemic immunohaematological disease is described here. This patient showed cutaneous lesions similar to the subacute form of systemic lupus erythematosus, severe anaemia and dysproteinaemia, and a marked reduction of circulating T lymphocytes, mainly the CD4+ cells. In vitro bone marrow cell culture studies showed that addition of patient's serum induced macrophage proliferation and inhibited erythroid progenitor cell growth. Treatment with high-dose intravenous immune globulin resolved most of the clinical and laboratory abnormalities.
Journal of Inherited Metabolic Disease 05/1998; 21(2):95-102. · 3.58 Impact Factor
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ABSTRACT: Two siblings presented with a new phenotype consisting of fatal progressive macrocephaly and hypertrophic cardiomyopathy. Onset of symptoms started in both patients at the end of the first month of life with massive brain swelling causing macrocephaly and evolving to extensive brain destruction. Light microscopy of the lesions showed extensive small-vessel proliferation and gliosis. A distinct deficiency of complex I of mitochondrial respiratory chain was established in cultured fibroblasts, skeletal muscle, and heart muscle. Specific lack of complex I protein was demonstrated by two-dimensional gel electrophoresis.
Annals of Neurology 11/1997; 42(4):661-5. · 11.09 Impact Factor
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ABSTRACT: Mitochondrial trifunctional protein deficiency, a recently identified disorder of fatty-acid oxidation, may show characteristic features such as peripheral neuropathy, pigmentary retinopathy, and acute fatty liver degeneration in pregnant women with an affected fetus. We describe a patient with trifunctional protein deficiency whose clinical picture consisted of severe calcium and phosphate abnormalities caused by hypoparathyroidism.
Journal of Pediatrics 08/1996; 129(1):159-62. · 4.11 Impact Factor
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ABSTRACT: We performed serial cranial ultrasonography in four newborns affected by maple syrup urine disease. Symmetric increase of echogenicity of periventricular white matter, basal ganglia (mainly pallidi), and thalami was detected in the acute stage. The degree of ultrasonography abnormalities paralleled the clinical course of the disease.
American Journal of Neuroradiology 03/1996; 17(2):311-5. · 2.93 Impact Factor
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Journal of Inherited Metabolic Disease 02/1995; 18(2):169-72. · 3.58 Impact Factor
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ABSTRACT: We describe four Italian male infants with a novel clinical phenotype characterized by orthostatic acrocyanosis, relapsing petechiae, chronic diarrhea, progressive pyramidal signs, mental retardation, and brain magnetic resonance imaging abnormalities. The first symptoms appeared after the termination of breast-feeding and introduction of formula feeding. Marked persistent 2-ethylmalonic aciduria was associated with abnormal excretion of C4-C5(n-butyryl-, isobutyryl-, isovaleryl-, and 2-methylbutyryl-)acylglycines and acylcarnitines and with intermittent lactic acidosis. Short- and branched-chain plasma acylcarnitine levels were also elevated. 2-Ethylmalonic aciduria is generally regarded as being indicative of a defect in fatty acid oxidation. Extensive studies of cultured fibroblasts failed to reveal such a defect. The observation of intermittent urinary excretion of 2-ethylhydracrylic acid pointed to involvement of the isoleucine R pathway in ethylmalonate biosynthesis. This hypothesis was tentatively corroborated by the biochemical responses to an oral isoleucine challenge in two patients. However, fibroblast studies showed normal oxidation rates of (14C)isoleucine (ul), indicating that this is not a defect of isoleucine oxidation expressed in skin fibroblasts. In one of two patients tested, cytochrome c oxidase activity was partially reduced (45%) in cultured fibroblasts. This unique clinical and biochemical phenotype identifies a new metabolic encephalopathy of yet undetermined cause.
Journal of Pediatrics 02/1994; 124(1):79-86. · 4.11 Impact Factor
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ABSTRACT: We report on a boy with several findings of the Meckel syndrome, such as hepatic fibrosis, polycystic kidneys, post-axial hexadactyly, and genital abnormalities, but a Dandy-Walker malformation rather an occipital meningocele. Progressive deterioration of renal function beginning at 37 months led to death at 43 months. Both Dandy-Walker malformation and survival to the fourth year are unusual findings in Meckel syndrome. This uncommon combination represents a further demonstration of the pleiotropy/heterogeneity of the cerebro-reno-digital syndromes.
American Journal of Medical Genetics 09/1993; 47(1):50-3.
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ABSTRACT: A 3-month-old girl was admitted to the hospital because of hypotonia and frequent vomiting. She had severe metabolic acidosis and her liver function was abnormal. Hepatomegaly and rapidly progressive liver failure developed, and she died at 4 months of age. Two half-siblings from a different mother had died in infancy of an undiagnosed myopathy. The liver was fatty and hepatocytes were filled with large and small lipid droplets. Other tissues were morphologically normal. The respiratory chain enzymes containing subunits encoded by mitochondrial DNA were markedly decreased in liver, partially decreased in muscle, but normal in other tissues. Southern blot analysis showed 90% depletion of mitochondrial DNA in liver, 53% depletion in muscle, and normal amounts in other tissues. This is the second case of fatal infantile liver failure associated with mitochondrial DNA depletion. This pathogenetic mechanism should be considered in infants with multiple respiratory chain defects and variable tissue expression.
Journal of Pediatrics 01/1993; 121(6):896-901. · 4.11 Impact Factor
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ABSTRACT: An 11-month-old girl presented acute episodes of hypoglycaemia and hepatic encephalopathy reminiscent of Reye syndrome and 3-hydroxydicarboxylic aciduria. The patient showed peculiar clinical manifestations of severe sensory-motor neuropathy, pigmentary retinopathy, and cardiomyopathy. She died of cardiac failure. Pathological studies of peripheral nerve showed signs of axonal neuropathy and demyelination. Enzymatic studies in cultured fibroblasts showed a deficiency of mitochondrial long-chain 3-hydroxyacyl-CoA-dehydrogenase. Peripheral nerve involvement and retinal pigmentary degeneration have as yet not been described in patients with proven defects of mitochondrial beta-oxidation.
European Journal of Pediatrics 03/1992; 151(2):121-6. · 1.88 Impact Factor
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The Lancet 01/1992; 338(8781):1522-3. · 38.28 Impact Factor
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Journal of Pediatrics 06/1991; 118(5):744-6. · 4.11 Impact Factor
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ABSTRACT: Hereditary fructose intolerance (HFI) is an inborn error of metabolism caused by aldolase B deficiency. The aldolase B gene has been cloned and the following mutations causing HFI have been identified: A149P (a G----C transversion in exon 5), A174D (a C----A transversion in exon 5), L288 delta C (a base pair deletion in exon 8), and N334K (a G----C transversion in exon 9). We have investigated the occurrence of these mutations in 11 Italian patients affected by HFI using PCR and hybridisation to specific oligomers. We found that four patients were homozygous for the A149P mutation, two patients were homozygous for the A174D mutation, three patients were compound heterozygotes for both the A149P and A174D mutations, one patient was homozygous for the N334K mutation, and one patient did not show any of the reported mutations (HFI diagnosis carried out by aldolase B assay). The L288 delta C mutation has not been found in this survey.
Journal of Medical Genetics 05/1991; 28(4):241-3. · 6.36 Impact Factor
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Acta paediatrica 11/1990; 79(10):978-9. · 1.77 Impact Factor
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Journal of Inherited Metabolic Disease 02/1990; 13(6):888-90. · 3.58 Impact Factor
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Journal of Pediatrics 05/1988; 112(4):678. · 4.11 Impact Factor
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Journal of Inherited Metabolic Disease 02/1988; 11(3):312-3. · 3.58 Impact Factor
