Systemic lupus erythematosus-like disease in a 6-year-old boy with prolidase deficiency.

This report describes the case of a boy with prolidase deficiency who presented with splenomegaly and leg ulcers. Laboratory examination revealed hypergammaglobulinaemia, hyperimmunoglobulinaemia E, increased erythrocyte sedimentation rate, elevated transaminases, positive antinuclear and anti-double-stranded DNA antibodies, and complement consumption. No haematological, renal or articular problems were detected; neutrophil count was normal. The skin lesions were thought to be of vasculitic origin, and a diagnosis of systemic lupus erythematosus was made although the requirements for diagnosis of systemic lupus erythematosus based on American Rheumatism Association criteria were not satisfied. The child was treated with immunosuppressive drugs with worsening of skin lesions before the diagnosis of prolidase deficiency. Prolidase deficiency and systemic lupus erythematosus share a number of common immunological features and at least three patients with prolidase deficiency and immunological and clinical findings fulfilling the diagnostic criteria for systemic lupus erythematosus of the American Rheumatism Association are reported in the literature. Here we review pathogenetic hypothesis linking the metabolic defect to the disturbance in immune function. In particular we discuss the role of highly increased rates of apoptosis and/or abnormal processing of apoptotic keratinocytes in prolidase deficiency and the role of C1q deficiency, which is associated with the failure of normal clearance of apoptotic cells bearing on their surfaces many of the autoantigens involved in systemic lupus erythematosus.

Isolated sulphite oxidase deficiency: clinical and biochemical features in an Italian patient.

A patient with isolated sulphite oxidase deficiency presented with seizures at 12 h of life and followed a severe course, dying at 10 months of age. There was mild facial dysmorphism and the brain showed multiple cystic fibrosis.

Long-term follow-up of a patient with mild tetrahydrobiopterin-responsive phenylketonuria.

We report on the long-term follow-up of the first Italian patient with the tetrahydrobiopterin (BH4)-responsive type of phenylalanine hydroxylase deficiency (R243X/Y414C genotype). The patient was diagnosed by the newborn screening for phenylketonuria (PKU) and with a positive BH4 loading test. Introduction of BH4 (initially 10 and later 20 mg/kg/day) in addition to reduced low-phenylalanine diet resulted in therapeutic plasma phenylalanine concentrations (<340 micromol/L). Very good compliance and no side effects in this patient demonstrate the great potential of BH4 in the treatment of some patients with mild PKU.

Pregnancy and tyrosinaemia type II.

A female patient with tyrosinaemia type II is reported having undergone two untreated pregnancies. During pregnancies, plasma tyrosine was raised. The outcomes of both offspring show that maternal tyrosinaemia may have an adverse effect on the developing fetus.

Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved they do not have deficient activity of methionine adenosyltransferase I/III. A variety of studies provided evidence that the elevations of methionine and AdoMet are not caused by defects in the methionine transamination pathway, deficient activity of methionine adenosyltransferase II, a mutation in methylenetetrahydrofolate reductase rendering this activity resistant to inhibition by AdoMet, or deficient activity of guanidinoacetate methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with elevated plasma AdoMet in normal subjects following oral methionine loads and in association with increased plasma levels of both methionine and AdoMet in cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is not elevated in these siblings. The latter result provides evidence they are deficient in activity of glycine N-methyltransferase (GNMT). The only clinical abnormalities in these siblings are mild hepatomegaly and chronic elevation of serum transaminases not attributable to conventional causes of liver disease. A possible causative connection between GNMT deficiency and these hepatitis-like manifestations is discussed. Further studies are required to evaluate whether dietary methionine restriction will be useful in this situation.

3-Methylglutaconic aciduria and hypermethioninaemia in a child with clinical and neuroradiological findings of Leigh disease.

We report on a child with a clinical and neuroradiological picture consistent with Leigh disease and an unusual association of isolated hypermethioninaemia and 3-methylglutaconic aciduria. A low-methionine diet normalized both plasma methionine and urine 3-methylglutaconic acid; a methionine-loading test led to significant increase of both metabolites. In the skin fibroblasts the activity of 3-methylglutaconyl-CoA hydratase was essentially normal. No explanation of this uncommon association of hypermethioninaemia and glutaconic aciduria is available. The possibility of a common transporter for 3-methylglutaconic acid and methionine is an attractive hypothesis.

[Evaluation of a new amino acid mixture for the treatment of phenylketonuria]. / Valutazione di una nuova miscela di aminoacidi per il trattamento della fenilchetonuria.

BACKGROUND: To assess the acceptability and nutritional adequacy of a new phenylalanine-free amino acid mixture (Phenylade-Dietetic Metabolic Food). METHODS: Twenty PKU patients (aged 2.6-10 years) diagnosed and followed by our Department. The children were given this product for a minimum of 4 and a maximum of 12 months. The clinical control has been carried out before treatment and then every 3 months. The biochemical parameters included: quantitative plasma amino acids, hematologic measurements of nutritional adequacy folic acid and vitamin B12. RESULTS: All patients (except one) found this new product to be an acceptable alternatives as to taste and convenience to the previous low phenylalanine protein substitutes. CONCLUSIONS: Normal growth was maintained.