Alpha-1-Antitrypsin Deficiency in Children-Unmet Needs Concerning the Liver Manifestation.

OBJECTIVES: This study aimed to analyse the clinical course of 45 children with severe alpha-1-antitrypsin deficiency (AATD) registered in our clinic to detect possible predictors of poor outcomes. METHODS: The clinical and biological data of 45 patients with homozygous or compound heterozygous AATD were analysed. The data were collected retrospectively going back to 2005 and prospectively from May 2020 until October 2021. It was based on questionnaires, laboratory values, sonography, and biopsy findings. Liver disease was classified into four grades depending on the grade of liver disease: mild or no liver disease, moderate disease, severe disease, and liver transplantation. RESULTS: Thirty-nine patients (86.7%) had a Pi*ZZ and five (11.1%) a Pi*SZ genotype. One patient showed a new, not-yet-described compound heterozygous genotype (Pi*Z + Asp95Asn). A total of 66.7% of the cohort showed mild or no liver disease, 20% moderate, and 13.3% severe. AATD was diagnosed in most cases because of liver abnormalities, such as the elevation of transaminases (42.2%). A total of 29.4% of the patients with neonatal icterus prolongatus developed severe liver disease, and 25.7% were born small for their gestational age (SGA). Diseases of the atopic type were reported in 47.4% of the cases. CONCLUSIONS: The presence of neonatal icterus prolongatus in the first weeks of life was significantly more likely in severe courses of liver disease (r = 0.371, p = 0.012). A tendency toward atopic comorbidity in AAT-deficient children needs to be further evaluated.

A classic twin study of lower urinary tract obstruction: Report of 3 cases and literature review.

OBJECTIVE: The aim of the present study was to investigate genetic effects in the formation of congenital lower urinary tract obstruction (LUTO) comprising posterior urethral valves (PUV), urethral atresia, and urethras with variable degrees of stenosis. METHODS: A classic twin study was performed by assessing LUTO twin pairs from the literature. Furthermore, data regarding 3 previously unreported twin pairs with PUV from University of Bonn, Essen and Wroclaws own in-house databases were added. Both pair- and probandwise concordance rates were calculated and compared for monozygotic (MZ) and dizygotic (DZ) twin pairs. RESULTS: The pairwise concordance rates for all LUTO were 53% (95% confidence interval [CI] 32%-73%) and 17% (95% CI 3%-56%) for MZ and DZ twin pairs, respectively (P = .180). The probandwise concordance rates were 69% (95% CI 51%-83%) and 29% (CI 95% 8%-64%) for MZ and DZ twin pairs respectively (P = .084). The MZ/DZ ratios of the pair- and probandwise concordance rates were 3.1 and 2.4, respectively. CONCLUSION: The present study did not show significant differences in comparisons of concordance rates of MZ and DZ twin pairs, probably due to the small number of twin pairs reported. However, the more than 2-fold higher pair- and probandwise concordance rates for MZ versus DZ twin pairs are very suggestive of a contribution of genetic factors to the development of LUTO.

Novel therapeutic approaches in primary hyperoxaluria.

Introduction: Currently, three types of primary hyperoxaluria (PH I-III) are known, all based on different gene-mutations affecting the glyoxylate metabolism in the liver. Disease hallmark is an increased endogenous oxalate production and thus massively elevated urinary excretion of oxalate and other type-specific metabolites. Hyperoxaluria induces the formation of calcium-oxalate kidney stones and/or nephrocalcinosis. In addition to that, a chronic inflammasome activation by hyperoxaluria per se, often leads to an early deterioration of kidney function, regularly resulting in end-stage renal disease (ESRD) at least in patients with type I PH. Except for vitamin B6 treatment in PH I, therapeutic regimen nowadays consists only of supportive measures, like significantly increased fluid intake and medication increasing the urinary solubility like alkaline citrate. Areas covered: Disease burden can be severe, and both clinicians and scientist are eager in finding new therapeutic approaches. The currently ongoing clinical studies and promising research in this field are reported in this paper. To present a complete overview, we searched electronic databases, like Clinical trial gov, National Center for Biotechnology Information PubMed, congress reports, press releases and personal information acquired at congresses and conventions. Searches were conducted using the following medical headings: (primary) hyperoxaluria, PH, therapy, treatment and research. Expert opinion: There is light on the horizon that new treatment options will be available in due time, as there are several promising therapeutic agents currently under investigation, some being at the first levels of drug development, but some already in ongoing clinical trials (phase I-III).

Congenital intrahepatic portocaval shunts and hypoglycemia due to secondary hyperinsulinism: a case report and review of the literature.

BACKGROUND: Congenital portosystemic shunts present with various associated complications, such as other congenital malformations, hyperammonemia, or hepatopulmonary syndrome. Few cases of associated hypoglycemia have been reported so far and our case, to the best of our knowledge, describes the most severe extent of hypoglycemia. CASE PRESENTATION: We describe the case of a newborn Arab boy with two intrahepatic portosystemic shunts, resulting in severe and persistent hypoglycemia, due to which one of the shunts was closed by interventional radiology whereas the other shunt had already closed spontaneously. CONCLUSIONS: Because he showed elevated levels for insulin and prolonged high insulin levels in an oral glucose tolerance test, our case supports the theory that portocaval shunts cause a reduced hepatic insulin reduction due to the high blood volume bypassing the liver. This case provides further insights into glucose regulation mechanisms of the liver and we suggest a consistent screening for hypoglycemia in patients with congenital portosystemic shunts.

Nephrolithiasis and Nephrocalcinosis in Childhood-Risk Factor-Related Current and Future Treatment Options.

Nephrolithiasis, urolithiasis, and nephrocalcinosis (NC) have become common causes of hospitalization and referral to pediatric outpatient clinics. It is of utmost importance to start with diagnostic evaluation directly after the first passage of a kidney stone, or if NC is diagnosed, in each pediatric patient. This is necessary, as in about 80% of children a metabolic reason for stone disease is detected. Current treatment options are scarce and mainly include general measures like an increased fluid intake or elevating the solubility of a lithogenic substance. According to the given lithogenic risk factor(s), specific treatment options are available and are being summarized in this review. Furthermore, an outlook on potential future treatment options, including innovative strategies such as mRNA-based or recombinant enzyme substitution therapy, is given.