Guanidinoactetate methyltransferase deficiency should be considered in patients with unexplained intellectual disability, and urinary guanidinoacetate should be determined as an initial diagnostic approach.

Background: Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by accumulation of lipoproteinaceous material within alveoli, occurring in three clinically distinct forms: congenital, acquired and secondary. Among the latter, lysinuric protein intolerance (LPI) is a rare genetic disorder caused by defective transport of cationic amino acids. Whole Lung Lavage (WLL) is currently the gold standard therapy for severe cases of PAP.

The investigation of a sample of 99 women on maintenance hemodialysis has shown the presence of sexual disturbances to a great extent: the rate of sexual intercourse and the ability to reach orgasm were significantly lower than in age-matched control women. 80% declared a reduction in their sexual desire and the frequency of intercourse was also lower as compared to the period prior to dialysis. Ageing decreased the sexual activity in both the ill and healthy population, but in uremic patients the sexual activity ended at an earlier age. The patients with hyperprolactinemia reported lower frequencies of intercourse and lower percentages of orgasm than normoprolactinemic ones. The incidence of sexual dysfunction and the role of hyperprolactinemia in this respect were similar to those which are found among male patients on hemodialysis.

aObjectives Hereditary fructose intolerance is caused by a deficiency of the aldolase B enzyme, which is expressed in the liver, small intestine and kidneys. Patients usually show a marked aversion to fruits and sweets; if, however, it is not diagnosed, persistent or incidental ingestion of fructose might be lethal. Our paper aims at improving the clinical and molecular characterizations of these patients, to avoid dangerous misdiagnoses.Methods Here we report the molecular results in an Italian cohort: on the occurrence of aldolase B mutations and, in particular, on the clinical and molecular characterization of a large family with recurrent hereditary fructose intolerance.Results Patients included in our cohort showed the three most common mutations (p.A150P, p.A175D and p.N335K). Such molecular tests were enough to cover all the mutated alleles of hereditary fructose intolerance found in our patients. The allele frequencies of hereditary fructose intolerance mutations detected were 69.2% for p.A150P, 23.1% for p.A175D and 7.7% for p.N335K. The proband of the family with recurrence of the disease was heterozygous for the known p.A150P and p.A175D mutated alleles of the aldolase B gene. Molecular characterization of at-risk family members also identified the p.N335K mutation. In addition, the oldest affected patients exhibited mild clinical impairment.Conclusions Our results indicate that the diagnosis of hereditary fructose intolerance can be complicated by clinical and genetic intrafamilial variability. A knowledge of the clinical and geographical history of each family member is thus essential, to reduce potentially lethal misdiagnoses and to facilitate such patients to receive appropriate genetic counselling.

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Among the inherited metabolic diseases presenting with lactic acidosis, pyruvate metabolism and respiratory-chain defects are the major clinical syndromes. To verify the Italian experience on this group of diseases, a survey was conducted throughout the Italian centres involved in study of inborn errors of metabolism. A questionnaire, established by a small group of promoters, was mailed to all Italian SSIEM members. This work presents the results of the collaborative study based on completed questionnaires.Seventy-two patients were identified, all with proven diagnosis either by enzyme or by molecular studies. Table 1 presents, for each centre, the number of the reported patients and the final diagnosis. DIAGNOSTIC APPROACHThe diagnostic procedures differed between centres, being linked to the local facilities and personal experiences. As well as the first-level investigations (including plasma and CSF lactate, pyruvate and ketone bodies, liver and kidney function, and muscular enzymes) amino acid and organic acid profiles were evaluated in most cases. In three centres the evaluation of oxidoreduction (redox) status (based on lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios in fasting and fed condition) was used for diagnostic purpose.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport (CAA), relatively common in Finland and Italy. After weaning, LPI patients present poor feeding, vomiting and failure to thrive. A severe pulmonary complication and episodes of metabolic imbalance may lead to death. Prenatal diagnosis has not been available due to lack of either biochemical or molecular markers to be used in the fetal period. The LPI locus has recently been assigned to chromosome 14q12, very close to the T-cell receptor alpha-chain (TCRA) locus. We carried out a prenatal diagnosis for LPI by linkage analysis in one LPI Italian family after CVS. For the haplotype analysis 11 DNA markers from the LPI critical region were used (D14S742, D14S50, D14S283, five TCRA intragenic polymorphic sites, D14S990, MYH7 and D14S80). It was concluded that the haplotype analysis indicated that the fetus was healthy as he had inherited the two wild alleles of the LPI locus. After birth, the clearances of CAA were measured and found to be in the normal range, thus confirming the result of the prenatal diagnosis. The prenatal diagnosis of LPI can now be offered to families affected by LPI.

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