A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia.

INTRODUCTION: distal renal tubular acidosis (dRTA) presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. CASE REPORT: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. CONCLUSIONS: blood and urine investigations and genetic tests are fundamental to formulate dRTA diagnosis and to plan follow-up, according to possible phenotypic expressions of recessive and dominant autosomal forms in patients with dRTA.

Molecular characterization of wilson disease in the Sardinian population--evidence of a founder effect.

Wilson disease (WD) in the Sardinian population has an approximate incidence of 1:7,000 live births. Mutation analysis of the WD gene in this population reported in our previous articles led us to the characterization of two common mutations and a group of 13 rare mutations accounting for the molecular defect of 8.5, 7.9, and 15.1% of the WD chromosomes. However, molecular analysis of the WD chromosomes containing the most common haplotype, which accounts for 60.5% of the WD chromosomes, failed to define the disease-causing mutation. In this study, we characterized the promoter and the 5' UTR of the WD gene sequence and carried out a mutation analysis in this DNA region from patients with the most common haplotype. The promoter is contained in a GC-rich island and shows a TATA and a CAAT consensus sequence as well as potential binding sites for transcription factors and metal response elements. In all the analyzed 92 chromosomes with this haplotype, we detected a single mutation consisting of a 15-nt deletion from position -441 to position -427 relative to the translation start site. Expression assays demonstrated a 75% reduction in the transcriptional activity of the mutated sequence compared to the normal control. By adding this mutation to those that have been already characterized, we have now defined the molecular defect in 92% of the WD chromosomes in Sardinians. The high frequency, the expected prevention by preclinical diagnosis and early treatment of the devastating effect of WD on the nervous system and liver tissue, and the feasibility to detect most of molecular defects by DNA analysis indicate that WD in the Sardinian population should be added to the list of diseases currently detected by newborn screening.

Value of histochemical stains for copper in the diagnosis of Wilson's disease.

AIMS: The histochemical demonstration of hepatic copper is important in the diagnosis of Wilson's disease (WD). Conflicting results have been published with regard to the ability of different histochemical methods to demonstrate copper storage in the liver. Therefore, we evaluated the diagnostic value of three available histochemical methods in a large series of patients affected by WD. METHODS AND RESULTS: Seventy-nine consecutive liver needle biopsies, from 74 patients, 39 males and 35 females, aged 4-60 years (mean age 28.5 years) were stained with orcein, rhodanine and using Timm's method. On the basis of the histological picture, liver biopsies were subdivided into three groups: group A, steatosis; group B, interface hepatitis; group C, chronic hepatitis with bridging fibrosis and/or cirrhosis. In group A, 30.4% of the cases were positive using Timm's method, vs 13.2% using the rhodanine and 17.5% using the orcein method. In group B, Timm's method was positive in 40.1% while rhodanine and orcein showed positivity in 26.7%. In group C, the Timm's method stained 58.6%, rhodanine 36.6% and orcein 29.3% positively. CONCLUSIONS: Our data show that: (1) Timm's silver stain is the most sensitive method for the demonstration of copper in all cases of WD; (2) rhodanine and orcein have minor value in the diagnosis of WD, especially in the early stages of the disease; (3) to increase the diagnostic value of histochemistry for copper multiple histochemical stains in serial sections are required; and (4) although hepatic copper concentration is highest in the early stages of WD, the histochemical demonstration fails in a large number of cases.

Congenital hepatic dysplasia from cytomegalovirus.

The Authors report on a case of liver dysplasia in a four-month-old infant affected by prenatal cytomegalovirus infection. Immunologic, histologic and ultrastructural studies suggest an embryopathic origin of the lesions.

[Acute disseminated histiocytosis X. Presentation of a case]. / Istiocitosi x acuta disseminata. Presentazione di un caso.

The AA. report a case of acute, diffuse histiocytosis X with an unfavourable course observed in a child of 33 months. The histological diagnosis, formulated on the basis of specimen taken from a skin nodule, was confirmed by ultrastructural observation of Birbeck bodies in the cytoplasm of proliferating Langerhans cells.

Carrier detection and early diagnosis of Wilson's disease by restriction fragment length polymorphism analysis.

Wilson's disease, a rare autosomal recessive disorder, has been recently mapped to the long arm of chromosome 13 (q14.1). In this study, we carried out linkage analysis between three chromosome 13 DNA markers, D13S1, D13S10, D13S2, the locus for the red cell enzyme esterase D (ESD), and the Wilson's disease locus (WND) in 17 Wilson's disease families of Italian descent, mostly from Sardinia. We confirmed a tight linkage [theta = 0.00, Z (theta) = 4.07] between the WND and ESD loci, and provided suggestive evidence for linkage [theta = 0.00, Z(theta) = 1.85] of the WND locus with D13S10. Multipoint linkage analysis indicated the following order: centromere-D13S1-D13S10-WND-ESD-D13S2. RFLP analysis at these two loci in our families allowed us either to define the carrier status (50%) or to exclude the homozygous state (25%) in the great majority of unaffected sibs.

[Osteomatosis of the skin. Presentation of 2 cases]. / Osteomatosi della cute. Presentazione di due casi.

Osteomatosis cutis. Report of two cases. The AA. reported two cases of osteomatosis cutis in a child three years old and in a girl sixteen years old. In both cases there was no history of previous trauma and acne. Microscopic study revealed islands of true bone, having lamellar configuration, periosteum, marrow cavities with endosteum, lacunae and canaliculae. No other calcified tissue and cartilage were seen.

[Syndactylia associated with multiple malformation syndromes. Observation of a new symptomatologic complex in 3 brothers]. / In tema di sindattilia associata a sindromi plurimalformative. Osservazione di un nuovo complesso sintomatologico in tre fratelli.

Hand and feet malformations are often part of complex malformation associations. The present paper reports on a family whose three sibs (two males and one female) are affected with symmetric soft tissue syndactyly involving both fingers and toes, fifth finger clinodactyly, a pattern of dysmorphism including down slanting palpebral fissures, long flat nasal saddle, out turned nostril openings ("Greek warrior helmet"-like profile), dysplastic teeth, and, in addition, severe growth retardation, microcephaly, severe mental deficiency with immaturity of cerebral activity of EEG, hypergonadotropic hypogonadism and some skeletal anomalies. All cases show large secondary constriction in one of the chromosome 1 pair (1qh+).

[Cytogenetic and clinical aspects of Prader-Willi syndrome]. / Contributo alla conoscenza degli aspetti citogenetici e clinici della sindrome di Prader-Willi.

Two male nonconsanguineous cases (aged 4 years) of Prader-Willi syndrome are clinically and cytologically studied. Both had obesity, marked hypogonadism, reduced head circumference, psychomotor impairment, hypotonia, tooth decay, small hands and feet, immature EEG. Case 1 showed a "de novo" translocation 7;15 and case 2 showed a normal karyotype. According to various authors, many cases of Prader-Willi syndrome show the presence of a translocation of chromosome 15 onto an autosome or X chromosome. This is the first observation of chromosome 7 involvement in this translocation.

[Wiedemann-Beckwith syndrome in childhood]. / Contributo alla conoscenza della sindrome di Wiedemann-Beckwith in età evolutiva.

A follow up examination was carried out in a 10 year old child who had been diagnosed as having Wiedemann-Beckwith syndrome soon after birth. Macrosomy was seen to persist and body asymmetry and some dysmorphic aspects had become more pronounced over the years. The presence of moderate mental deficiency had led to difficulty in social relationships. In the prepuberty phase, the reappearance of hypoglycemia crises, which were also noted in the neonatal age, was of particular interest.

[Aspects and behavior of x-ray computed tomographic studies in subacute sclerosing panencephalitis]. / Aspetti e comportamento dell'indagine tomodensitometrica nella panencefalite sclerosante subacuta.

The authors reports cerebral Computerized Axial Tomography findings examined, in association with other diagnostic tests, in 5 cases of Subacute Sclerosing Panencephalitis in the acute phase and repeated in 2 of these patients later, during the state and terminal phases of the disease. Hypodensity of the white matter was the main sign of initial cerebral parenchymal involvement and an atrophic aspect was most indicative of the terminal phase. Moreover, it has been shown that associated with clinical symptomatology, immunologic data and EEG signs, cerebral Computerized Axial Tomography may offer the possibility for evaluating the nature and the evolutive stage of the disease and facilitate differential diagnosis from other degenerative encephalopathies.

Epidemiologic study of hepatolenticular degeneration (Wilson's disease) in Sardinia (1902-1983).

From 1902 to 1983, 68 cases of hepatolenticular degeneration (HLD) were discovered in Sardinia, with a mean frequency, in reference to number of live births, of 27.7 and a sex ratio of 1.83. The prevalence of the disease was seen to be higher over the last few decades. With regard to the geographic distribution of the disease, 3 high-frequency areas were evident, in Barbagia, in Campidano, and in the area surrounding the city of Sassari. In 38.23% of cases, the clinical picture was of hepatoneurologic type; hepatic forms have become more frequent over the last decades. The first symptoms were observed at mean age of 15 years 8 months. The number of asymptomatic cases was fairly consistent (22.05%). The median survival rate in subjects who received inadequate therapy was 6 years 4 months. Only 3 patients of the 45 treated with adequate therapy died. The gene frequency, calculated by the application of Dahlberg's formula, was extremely high.

[Opsoclonic encephalopathy in childhood (Kinsbourne syndrome)]. / L'encefalopatia opsoclonica nell'infanzia (sindrome di Kinsbourne).

Kinsbourne's syndrome (ataxia--opsoclonus--myoclonus) is described. The characteristics of this syndrome are: infections of the upper respiratory tract and enteric system and behavioural disturbances leading to the typical symptomatological triad. Various tests were carried out to determine the presence of neuroblastoma which is often associated (46%) to this syndrome. These tests resulted negative. Differential diagnosis was considered in relation to other conditions which present a characteristic symptomatology similar to Kinsbourne's syndrome. Synthetic ACTH (Synacthen) treatment produced a regression of the clinical symptoms. Based on the examinations carried out, which always resulted negative even after 36 months, and on the drug dependence, the present case was diagnosed as primitive opsoclonus.

Adrenal androgens in obese boys before and after weight loss.

The adrenal steroid secretion was studied in 6 prepubertal obese boys and 6 obese boys at the first stage of sexual maturation according to Tanner. Twelve normal boys, closely matched for age and stage of sexual maturation, were also studied as controls. Pregnenolone and dehydroepiandrosterone plasma levels were found to be significantly (P less than 0.001) higher in both groups when compared with normal boys. All the values, apart from pregnenolone in the prepubertal group, returned to normal after weight loss. Progesterone was found significantly increased (P less than 0.001) in both groups and normal after weight loss. 17-OH-progesterone plasma levels showed no significant difference between the obese and control groups. Androstenedione was increased in the prepubertal group before and normal after weight loss; no significant difference was found in the other group. Testosterone and estradiol showed normal values in the two groups both before and after weight loss. Cortisol showed a similar pattern. It can be concluded that an increased cortico-adrenal activity is present in obese boys as already reported in obese girls. This finding could explain the precocious adrenarche which often occurs in these patients. The increased adrenal androgen secretion might be due to an increased cortico adrenal stimulating hormone secretion or to an enhanced adrenal sensitivity to this hypothetical hormone.

Sexual maturation and adrenal function in girls with thalassemia.

Adrenal steroid production was evaluated in 12 thalassemic girls aged between 18 and 22 years and at stage P1 of sexual maturation according to Tanner. The values found in these patients were compared with those in 12 normal girls of the same age at stage P4-5 of sexual maturation. Pregnelone, dehydroepiandrosterone, dehydroepiandosterone sulfate, progesterone, 17-OH-P, androstenedione, testosterone, dihydrotestosterone and estradiol were found to be significantly reduced (p less than 0.001) in the thalassemic group, while cortisol levels showed a slight but not statistically significant reduction. Plasma ferritin levels were greatly increased and showed a highly significant (p less than 0.001) correlation coefficient when plotted against each hormone. The present results suggest that the impaired adrenal function plays an important role in determining the delayed sexual maturation almost always present in the thalassemic patients and that this disorder may be due to iron overload.

[Cutaneous, radiologic and endocrinologic aspects of adrenoleukodystrophy]. / Su alcuni aspetti cutanei, radiologici ed endocrinologici della adrenoleucodistrofia.

A case of adrenoleucodistrophy in a 9 year old boy is reported. At onset, strabismo, skin hyperpigmentation, difficulty in deambulation and retarded writing and language capability were seen. The child's condition rapidly worsened. Normal hemochrome, urine tests, azotemia, blood calcium levels, alkaline phosphate, aminoaciduria and lipidogram values were found. EEG showed diffused slow activity mainly bilaterally at the anterior deviations. TAC revealed hypodense grey matter, especially in the parietal zone, a typical finding in leucodystrophy (Cattarossi e coll., 1981). Cellular biopsy showed modifications of the fibrocells, considered indicative of this condition. The study of the hypothalamic hypophyseal - adrenal - gonadal axis showed a significant increase of LH and RH after stimulation, increased testosterone and androstenedione and reduced basal plasma cortisol, and after stimulation, levels. These findings suggest that hyposurrenalism may be secondary to 21 - hydroxylase deficiency.

A genetic combination of silent beta-thalassaemia, high Hb A2 beta-thalassaemia, and single alpha globin gene deletion causing mild thalassaemia intermedia.

This paper reports a Sardinian patient, who was a compound heterozygote for silent beta-thalassaemia and high Hb A2 beta o-thalassaemia with the clinical phenotype of mild thalassaemia intermedia; alpha globin gene mapping showed a single alpha globin gene deletion. The reduced alpha globin chain output resulted in more balanced globin chain synthesis, which in turn accounted for the mild clinical phenotype.

Adrenal and testicular function in boys affected by thalassemia.

The adrenal androgen secretion and testicular function were studied in 6 thalassemic boys aged between 16 and 20 years. Six normal boys of the same age and 6 at the same pubertal stage (P1 according to Tanner) were also studied as controls. Plasma testosterone levels were found significantly lower (p less than 0.001) in the thalassemic boys (0.8 +/- 0.1 ng/ml) than in healthy boys of the same age (3.4 +/- 1.01 ng/ml), but within the range of the healthy boys at the same pubertal stage (0.69 +/- 0.1 ng/ml). DHA-S, a marker of adrenal maturation, showed a similar pattern. The hCG test showed a significant (p less than 0.001) testosterone response in all 3 groups. The response of thalassemic boys (1.5 +/- 0.18 ng/ml) was similar to that of normal boys at stage P1 (1.8 +/- 0.31 ng/ml), but significantly lower (p less than 0.001) than the group of normal boys of the same age (12.5 +/- 3.2 ng/ml). The impaired adrenal and testicular activity is probably due to iron deposits in the endocrine glands.