Israel Medical Association Journal

Background: Treatment of patients with childhood growth hormone deficiency is usually terminated at the end of puberty. Follow-up into adult age is rare, even more so in patients with congenital isolated growth hormone deficiency (cIGHD).

Objectives: To assess the clinical and social characteristics of adults with cIGHD who received growth hormone (hGH) treatment in childhood.

Methods: Thirty-nine patients (23 men, 16 women) diagnosed in our clinic with cIGHD at 7 ± 4.2 years, and treated with hGH during childhood for 2–18 years, were followed into adulthood (mean age 30.7 ± 13.3 years). Ascertained detailed data were found for 32 patients.

Results: Mean ± SD height for males was 160.2 ± 10.6 cm and for females 146.4 ± 5.4 cm. All patients achieved full sexual development and 14 were married. After cessation of GH treatment and with advanced age all exhibited a progressive increase in adiposity to the degree of obesity. Twelve patients suffered from hyperlipidemia, 4 developed diabetes mellitus, and 5 have cardiovascular diseases. One patient died in an accident. None developed cancer. Of the 39 patients, 22 have an education level of high school or higher, and 2 are in special institutions. Most are employed in manual labor.

Conclusions: Patients with congenital IGHD who do not receive early and regular replacement treatment are prone to lag in achieving normal height and suffer from educational and vocational handicaps.

The question of who discovered insulin is controversial. One of the scientists working on pancreas extracts was Nicolae Paulescu, the so-called Forgotten Man. In addition to his scientific research he was also active in politics. He was the father of the virulent antisemitic fascist movement “Garda de Fer” in Romania; he raved against the “Jewish Peril,” claimed in his writings that the Jews are a genetically degenerate people trying to cheat and poison the Rumanian people by alcoholism, and more. His name came up in 2003 when Romanian diabetologists initiated a move to honor him. But voices rose in protest, claiming that persons who incite hatred, support persecution and genocide and distort science as their political tools cannot be accepted or rewarded. The protesters won.

Objectives: To compare the seasonality of children with T1DM in different populations around the world for which data were available.

Methods: We analyzed large cohorts of T1DM patients with a clinical disease onset before age 14 or 18 years.

Results: We found a seasonality pattern only in ethnically homogenous populations (such as Ashkenazi Jews, Israeli Arabs, individuals in Sardinia and Canterbury, New Zealand, and Afro-Americans) but not in heterogeneous populations (such as in Sydney, Pittsburgh and Denver).

Conclusions: Our findings attempt to explain the controversial data in the literature by showing that ethnically heterogeneous populations with a mixture of patients with various genetic backgrounds and environmental exposures mask the different seasonality pattern of month of birth that many children with diabetes present when compared to the general population.

Background: Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH[1] receptor gene.

Objective: To characterize the molecular defects of the GH-R[2] in Laron syndrome patients followed in our clinic.

Methods: Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques.

Results: Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described.

Conclusions: This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.

Background: Growth retardation in childhood was only recently recognized as a prominent feature of Gaucher disease type 1, but there are few data on both the pubertal development and the final outcome of growth and sexual maturation.

Objective: To investigate the natural pattern of growth and puberty in patients with Gaucher disease type 1 and the effect of splenectomy and enzyme replacement therapy.

Methods: We retrospectively analyzed growth and puberty in 57 patients with Gaucher disease type 1; 52 were followed since childhood and/or prepuberty and 42 have reached sexual maturity and final height. In the analysis we considered severity of disease, time of splenectomy, and start of enzyme replacement therapy.

Results: Deceleration of growth at age 3–5 years was observed in 30 of 57 patients followed since early childhood while untreated: height-SDS decreased from -0.34±0.42 at age 0–3 years to -1.93±0.95 (P<0.01) at age 7–10 years and was more pronounced with severe disease. A high prevalence (59.6%) of delayed puberty, which was more frequent with severe disease, was observed in 47 patients followed before and throughout puberty. No primary endocrine pathology was found. All patients, untreated as well as treated, with growth and pubertal delay had a spontaneous catch-up, achieved full sexual maturation, and most (83.3%) reached a final height within the range of parental height–standard deviation score. Splenectomy (partial and/or total) performed in 20 patients while still growing had a beneficial effect on growth, which was temporary in some and did not affect puberty. ERT improved growth in 11 patients who started therapy before puberty, as evidenced by a progressive increase in the height-SDS, and seemed to normalize the onset of puberty.

Conclusions: Growth retardation in childhood and delay of puberty are characteristic of Gaucher disease type 1 and are more frequent with severe disease. There is a spontaneous catch-up later in life and most patients reach a final height within their genetic growth potential. Enzyme replacement therapy apparently normalizes growth and possibly also the onset of puberty.

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ERT = enzyme replacement therapy

SDS = standard deviation score