A girl with diabetes and severe combined immunodeficiency from adenosine deaminase deficiency.

We present a girl with severe combined immunodeficiency (SCID) from adenosine deaminase (ADA) deficiency who developed insulin dependent diabetes mellitus (IDDM). This combination of features has not been previously reported. Because HLA typing (DQbeta-57 Asp/Asp and DQalpha-52 Ser/Ser) showed no alleles usually associated with IDDM, and ICA were repeatedly negative even after treatment with PEG-ADA and gene transplant, hypotheses on the pathogenesis of diabetes mellitus in this patient are discussed.

Spontaneous and mitomycin-C-induced micronuclei in lymphocytes from subjects affected by Turner's syndrome.

Peripheral blood lymphocytes from 15 subjects affected by Turner's syndrome (TS) and aged between 2 and 24 years (mean age 10.40 +/- 6.25) were tested to evaluate the spontaneous and Mitomycin-C-induced (MMC) micronucleus (MN) frequency. A group of 15 healthy subjects, in the same range of age (mean age 14.67 +/- 8.30), was also tested as control. As expected, statistically significant differences between spontaneous and MMC-induced MN were found either in TS and in healthy subjects. Unexpectedly, when the two groups of donors were compared, TS subjects showed a lower spontaneous and MMC-induced MN frequency, in comparison with healthy subjects. Cell proliferation kinetic and cytotoxicity were also measured applying the cytokinesis-block proliferation index (CBPI): the results show that MMC, at the employed concentration, does not induce cell cycle delay both in healthy and in TS donors. Whereas, when CBPI from TS and healthy donors were compared, a faster proliferation was found in TS patients in both untreated and MMC-treated cultures.

Insulin-dependent diabetes mellitus and severe atopic dermatitis in a child with adenosine deaminase deficiency.

We report a 2.3-year-old girl with complete lack of adenosine deaminase (ADA) activity who presented with severe atopic dermatitis and insulin-dependent diabetes mellitus but only mild recurrent infections. Abnormalities of immune function included profound depletion of CD8+ lymphocytes, hyperimmunoglobulinaemia E, and very low in vitro proliferative response to mitogens. Treatment with polyethylene glycol-conjugated ADA was followed by rapid amelioration of clinical and immunological conditions. The immunological and clinical features of this child suggest that the clinical spectrum of ADA deficiency may be broader than originally supposed.

Seckel syndrome: report of three sibships with the type I primordial dwarfism. Possible linkage with HLA locus.

The authors report on five cases of Seckel syndrome type I primordial dwarfism, belonging to three unrelated sibships. Immunological and cytogenetic investigations with DEB test did not evidence immunodeficiency or chromosomal fragility. HLA phenotype studies revealed an identical haplotype in affected sibs: a possible linkage with HLA is therefore suggested. Cranial magnetic resonance was performed in three patients and did not evidence any anomaly. One affected female showed precocious puberty at 7 years of age.

Characteristics of insulin resistance in Turner syndrome.

The characteristics of insulin resistance, in Turner syndrome are still unclear. For this purpose in 4 patients with Turner syndrome and in 8 control females we performed an euglycaemic hyperinsulinemic glucose clamp at the following insulin infusion rates (50 and 100 mU/Kg x h), each period lasting 120 min. A simultaneous infusion of D-3-H-glucose allowed us to determine in basal conditions and during the clamp hepatic glucose output and glucose disappearance rate (Rd). In basal conditions plasma glucose (4.8 +/- 0.1 vs 4.6 +/- 0.2 mmol/1 p = NS) and plasma glucagon (102 +/- 7.5 vs 112 +/- 11.3 ng/l p = NS) were similar in both groups despite higher plasma insulin (19 +/- 1.8 vs 7 +/- 2.2 mU/l p less than 0.05) and C-peptide (1.0 less than 0.1 vs 0.8 +/- 0.06 pmol/l p less than 0.05) levels in patients with Turner syndrome. In the last 60 min of the lower insulin infusion rate glucose infusion rate (4.1 +/- 0.3 vs 2.9 +/- 0.4 mg/Kg x min p less than 0.05) and glucose disappearance rate (3.89 +/- 0.12 vs 2.63 +/- 0.11 mg/Kg x min p less than 0.01) were significantly reduced in patients with Turner. On the contrary hepatic glucose output was similarly suppressed in both groups of subjects. Doubling the insulin infusion rate, we obtained similar results in patients and controls respectively. So we conclude that in Turner syndrome the insulin resistance state is mainly due to a muscular receptor defect.

Gyrate atrophy of choroid associated with hyperornithinaemia: report of the first case in Italy.

The first case in Italy and the youngest case in the world of gyrate atrophy of the choroid associated with hyperornithinaemia is reported. A therapeutical attempt has been made and the possibility of following the evolution of the ocular lesion is very interesting.

Hyperornithinemia and gyrate atrophy of choroid and retina. Report of a case.

A case of hyperornithinemia and gyrate atrophy of choroid and retina has been observed in a 3-year and 9-month-old girl. She presented also mild mental retardation, delayed language development and speech defects. The restriction of protein intake to a minimum of 0.8 g/kg/day induced a significant reduction of plasma ornithine levels. In some of the previous reports of the syndrome, a deficient ornithine-ketoacid transaminase activity has been found in cultured fibroblasts.

Lysine in treatment of hyperornithinemia.

A metabolic study in a case of hyperornithinemia with gyrate atrophy of choroid and retina is presented. It is demonstrated that the lysine-ornithine antagonism is a physiological, safe, easy to handle therapeutic tool in hyperornithinemia. A lysine load was invariably associated with a reduction of plasma ornithine concentration. This happened at any level of protein intake. It was also shown that diets containing a low protein intake are invariably associated with negative nitrogen balance.