Maria Valeria Merlino

Cadmium concentration in maternal and cord blood and infant birth weight: a study on healthy non-smoking women.

Abstract The aim of our study was to measure, at delivery, maternal and cord blood cadmium levels (by means of atomic absorption spectrometry) in 45 healthy non-smoking pregnant women exposed to a low cadmium challenge, and to evaluate the relationship between these cadmium levels and the birth weight of the infants. Our results showed fairly low cadmium levels in maternal blood, in accordance with the fact that all women enrolled in this study lived in areas with low toxic metal contamination and that they did not smoke during their pregnancy. Furthermore, a highly significant direct correlation was found between maternal and cord blood cadmium concentrations. Since cadmium concentration appeared of the same order of magnitudine both in cord and maternal serum, one could speculate that cadmium is transferred easily from the mother to the fetus through the placenta. Finally, we found that birth weight is inversely correlated with maternal and cord blood cadmium concentrations; thus birth weight might be negatively influenced by cadmium levels as a result of the toxic effects of the metal on the placenta. Although preliminary, our data show that (also not-predictable) prenatal exposure to even low cadmium levels might be a risk factor for developmental impairment in infants.

Disomy of distal Xq in males: case report and overview.

A 46,XYq 8‐year‐old male was referred for microcephaly, growth, and mental retardation, hypotonia, genital hypoplasia, and dysmorphisms. FISH analysis showed that the rearranged Y chromosome originated from an unbalanced translocation of Xq27.3‐qter onto the deleted Yq11.22. Analysis of reported patients with disomy of region distal to Xq26 suggests that this rare anomaly, associated with failure to dosage compensate X‐linked genes that are normally inactivated, when present in two copies, is causing a quite distinct phenotype. This imbalance is the aberrant by product of the recombinogenic pairing of the distal pseudoautosomal Xq–Yq region at male meiosis.

Familial chronic nail candidiasis with ICAM-1 deficiency: a new form of chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis (CMC) includes a group of rare disorders with altered immune responses, selective against Candida, characterised by persistent and/or recurrent infections of the skin, nails, and mucous membranes, caused by organisms of the genus Candida, mainly Candida albicans . Familial occurrence of CMC was originally reported by Wells et al ,1 who described both males and females affected and consanguinity in a number of their pedigrees. The classification of CMCs is based on clinical features and pattern of inheritance, which can be either autosomal dominant or recessive (table 1). Most CMC types have an early age of onset, affect skin, nails, and mucous membranes, and are associated with altered phagocytosis and chemotaxis. The classical form of CMC does not include endocrinological diseases, which represent a major component of the immune polyendocrinopathy syndrome (APECED, MIM *240300), caused by mutations of the autoimmune regulator gene ( AIRE ) on chromosome 21q22.3.2,3 View this table: Table 1 Classification of CMCs We describe a distinct form of familial chronic candidiasis (FCNC), characterised by early onset infections caused by different species of Candida, restricted to the nails of the hands and feet, associated with low serum concentration of intercellular adhesion molecule I (ICAM-1). The family originates from a rural village in Sicily and includes 11 affected subjects in five generations (fig 1). Based on clinical and anamnestic records, III.8 was the first affected member of this family. She developed nail dystrophy, presenting with hyperkeratosis and dark and thick nails, similar to those found in other family members. IV.5, a 71 year old female, was unaffected. V.4, a 48 year old female, was a blood relative of her husband. From the age of 6 months, she was affected by onycomycosis caused by Candida involving all the nails of her hands and feet (figs 2 and 3). Caustication was …

A mitochondrial DNA mutation (A3243G mtDNA) in a family with cyclic vomiting

We report the incidence of mitochondrial DNA (mtDNA) mutations and/or deletions in a family from Southern Italy in which four members were affected by a cyclic vomiting syndrome (CVS). The A3243G mtDNA mutation was detected in a boy, his mother, maternal grandmother, and aunt but not in other relatives of the family. Patients with a CVS experience a minimum of three distinct episodes of vomiting and nausea, usually involving more than four emeses in one hour at the peak. They feel quite well between episodes. There is no apparent underlying cause for the vomiting [4]. In the differential diagnosis of CVS, mtDNA mutations should be considered when there is a maternal history of CVS and migraine, clinical findings of seizures, neuromuscular and gastrointestinal symptoms and laboratory evidence of lactate increase [5]. A family was recruited with four members suffering from CVS: a 5-year-old boy, his mother, the maternal grandmother and aunt. The three adults were affected by CVS during childhood, whilst they suffered from migraine at an adult age (Fig. 1). Metabolic investigations revealed permanent hyperlactataemia (5–8 mM) with elevated lactate/pyruvate ratios (L/P) (25–30) in the boy’s mother. In the maternal grandmother and aunt, lactate levels (2.6 and 3.0 mM respectively) were slightly elevated and L/P molar ratios remained in the normal range. The young patient suffered from vomiting fits which lasted for many hours until spontaneous resolution and recurrence with the same characteristics after an interval of 15–20 days. Metabolic acidosis (pH 7.3, bicarbonate 16 mM) with hyperlactataemia (2.5–5.35 mM) and elevated L/P (19–32; normal <16) and ketone body molar ratios were found (2–4.6, normal <2). Hyperalaninaemia, lactic aciduria, and an abnormal excretion of suberic, adipic, and 3-hydroxybutyric acids was observed. Laboratory, clinical and instrumental findings of all four patients excluded organic diseases. To check for point mutations and for a previously described 8.1 kb deletion [3], the region between nucleotides 6687 and 15123 was amplified by the polymerase chain reaction (PCR) in ten overlapping segments and completely sequenced. Screening for the 3243 np mutation in mtDNA was carried out by PCR-RFLP. The relevant region of mtDNA was amplified using the following primers according to the Cambridge sequence [1]: 5’CCCACAGGTCCTAAACTACC-3’ (np 2770–2789) and 5’AGCGAAGGGTTGTAGTAGCC-3’ (np 3456– 3437). The PCR products (10 ll) were then purified and digested with 15 U of the restriction endonuclease ApaI for 1 h at 32 C. The A-to-G mutation at 3243 np created an ApaI restriction site (GAGCCC to GGGCCC) and was easily detected by ethidium bromide staining in a 2.5% agarose gel. In order to detect small amounts of mutated mtDNA in the presence of an excess of wildFig. 1 Pedigree of the family with CVS; the arrow indicates the index case. The percentage of mutated mtDNA in blood and muscle of the patients is I:2=25% and 30%; II:2=35% and 38%; II:3=30% and 32%; III:1=70% and 75% respectively. Affected individuals are indicated by solid symbols Eur J Pediatr (2003) 162: 727–728 DOI 10.1007/s00431-003-1280-1

Hallerman-Streiff syndrome: patient with decreased GH and insulin-like growth factor-1.

We observed a 10-year-old boy with Hallerman– Streiff syndrome (HSS). The proband was the second child of healthy non-consanguineous parents. Family history was unremarkable. Pregnancy was uncomplicated and delivery at term with normal birth weight and length. There was mild psychomotor retardation. On physical examination, the child showed short stature (123 cm, 2.4 SD) with a distinctive triangular bird face. The head was brachycephalic with frontal bossing sparse curly and thin scalp hair. The eyebrows were hypoplastic. The palpebral fissures were short and downslanted with telecanthus and sparse eyelashes. The nasal bridge was narrow, the nose small with a rather beaked appearance and hypoplastic alae nasi. The philtrum was long and mouth small with thin lips. Palate was high arched. There was a distinct maxillary and mandibular hypoplasia. Malocclusion, prominent upper incisors, and dental crowding were quite remarkable. The ears were slightly low set with prominent ear lobes. Hands and feet were small with clinodactylous of 5th fingers. Distal interphalangeal joints of fingers and toes were enlarged. Laboratory tests, including extensive metabolic studies and karyotype yielded normal results. X-ray of left hand and wrist documented retarded bone age (8.5 years vs. 9.6 of chronologic age). Repeated insulin-like growth factor-1 (IGF-1) blood determinations disclosed constantly decreased levels in the range of 39–66.8 ng/ml (normal levels 128–458 ng/ml). The GH response to pharmacological stimuli yielded abnormal results with maximal levels of 5.8 ng/ ml after insulin stimulus and 8.5 ng/ml after clonidine stimulus (the maximal response must exceed 10 ng/ml). An ophthalmologic examination documented myopia and disclosed normal fundus oculi (Figs. 1–3). Short stature is a common feature in this syndrome, but to our knowledge, a deficiency of GH and IGF-1 has

Confirmation of Nablus mask-like facial syndrome.

We observed a little girl presenting with striking facial appearance. Since her diagnosis was not obvious, we discussed this patient at the Curbstone Consultations during the 52nd Annual Meeting of the American Society of Human Genetics in Baltimore. We came up with the conclusion that she was a second example of Nablus mask-like facial syndrome [Teebi, 2000, 2001]. A 21-month-old girl was the only daughter of healthy parents originating from a small village in northeast of Sicily. Careful pedigree analysis could not support parental consanguinity. Family history was unremarkable. Pregnancy was normal, while delivery at term was complicated by prolonged labor, which resulted in perinatal distress and right arm brachial plexus palsy. Birth weight was 3,650 g (75th–90th centile), length 48 cm (3rd centile), OFD 34 cm (10th centile). Apgar was 7 and 9 at 1 and 5 min. She had a distinct facial appearance with hypertelorism, blepharophimosis, and abnormal ears. At birth the baby underwent several investigations including ECG, echocardiogram, ultrasound of brain and abdomen, and standard karyotype, which were all unremarkable. Head control was reached at 3 months, first monosyllables at 14 months, walking unsupported at 16 months. Teeth eruption was normal, while abnormalities of size, position, and morphology were recorded. Ophthalmologic examination showed normal fundus oculi. On physical examination at the age of 21 months (Fig. 1a,b), height was 76 cm (25th centile), weight 10,850 g (25th centile), OFD 42.5 cm (<<3rd centile). The head was asymmetric with reduced antero-posterior diameter, upswept frontal hair, mild frontal bossing, and temporal constriction, flat supraorbital ridges, high-arched, sparse, and misaligned eyebrows. She had a distinct expressionless facial appearance, due to tight glistening facial skin, with impressive blepharophimosis, short and circumflexed opening of palpebral

A gene for familial isolated chronic nail candidiasis maps to chromosome 11p12-q12.1.

Chronic mucocutaneous candidiases (CMC) are a group of rare disorders where an altered immune response against Candida leads to persistent and/or recurrent infections of the skin, nails, and mucous membranes. We analysed a five-generation Italian family with an isolated form of CMC, affecting nails only, in the presence of low serum concentration of intercellular adhesion molecule I (ICAM-1). We excluded linkage to candidate regions on chromosomes 2p (CMC with thyroid disease), 21q22.3 (APECED), and 19q13 (ICAM-1). We then carried out a genome-wide scan and assigned the CMC locus to a 19 cM pericentromeric region on chromosome 11.

Serum levels of malondialdehyde and 4-hydroxy-2,3-nonenal in patients affected by familial chronic nail candidiasis.

Summary.Familial chronic nail candidiasis (FCNC.MIM 607644) is a rare disorder characterized by early onset infections caused by different species of Candida and restricted to the nails; this disorder is genetically associated with low serum concentration of intercellular adhesion molecule 1 (ICAM-1). Herein we report the evidence of high circulating levels of malondialdehyde (MDA) and 4-hydroxy-2,3-nonenal (HNE) in seven patients of a five-generation Italian family affected by FCNC.MIM 607644. The present data evidence, in these patients, an increase in circulating MDA and HNE levels. Only some merely speculative hypotheses may be suggested to explain the mechanisms subserving the oxidative stress condition observed in these genetically ICAM-1 deficient patients; however, one has to point out that a chronic oxidative stress condition could contribute to the development of concurrent pathological alterations in which an overproduction of free radicals may play a central role.

Protein carbonyl group content in patients affected by familiar chronic nail candidiasis.

Familiar chronic nail candidiasis (FCNC) is a rare disorder characterized by early-onset infections caused by different species of Candida, restricted to the nail of the hands and feet, and associated with a low serum concentration of intercellular adhesion molecule 1. Host defense mechanisms against candidiasis require the cooperation of many immune cells through several candidacidal mechanisms, including oxygen-dependent killing mechanisms, mediated by a superoxide anion radical myeloperoxidase--H2O2--halide system, and reactive nitrogen intermediates. We analyzed protein carbonyl groups (considered a useful marker of oxidative stress) in the serum of patients belonging to a five-generation Italian family with an isolated form of FCNC. Serum protein carbonyl groups in FCNC patients were significantly lower than those measured in healthy donors. Also, if this hypothesis is merely speculative, we could suggest that the decreased circulating level of protein carbonyl groups in these patients is not a marker of a lower oxidative stress condition, but might be linked to a lower protease activity.