100 years of inherited metabolic disorders in Austria-A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021.

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare disorders characterized by disruption of metabolic pathways. To date, data on incidence and prevalence of IMDs are limited. Taking advantage of a functioning network within the Austrian metabolic group, our registry research aimed to update the data of the "Registry for Inherited Metabolic Disorders" started between 1985 and 1995 with retrospectively retrieved data on patients with IMDs according to the Society for the Study of Inborn Errors of Metabolism International Classification of Diseases 11 (SSIEM ICD11) catalogue. Included in this retrospective register were 2631 patients with an IMD according to the SSIEM ICD11 Classification, who were treated in Austria. Thus, a prevalence of 1.8/10 000 for 2020 and a median minimal birth prevalence of 16.9/100 000 (range 0.7/100 000-113/100 000) were calculated for the period 1921 to February 2021. We detected a male predominance (m:f = 1.2:1) and a mean age of currently alive patients of 17.6 years (range 5.16 months-100 years). Most common diagnoses were phenylketonuria (17.7%), classical galactosaemia (6.6%), and biotinidase deficiency (4.2%). The most common diagnosis categories were disorders of amino acid and peptide metabolism (819/2631; 31.1%), disorders of energy metabolism (396/2631; 15.1%), and lysosomal disorders (395/2631; 15.0%). In addition to its epidemiological relevance, the "Registry for Inherited Metabolic Disorders" is an important tool for enhancing an exchange between care providers. Moreover, by pooling expertise it prospectively improves patient treatment, similar to pediatric oncology protocols. A substantial requirement for ful filling this goal is to regularly update the registry and provide nationwide coverage with inclusion of all medical specialties.

Exocrine Pancreatic Insufficiency in Type 1 and Type 2 Diabetes.

PURPOSE OF REVIEW: Type 1 and type 2 diabetes are often accompanied by mostly mild forms of exocrine pancreatic insufficiency. Despite high prevalence, little is known about the clinical consequences of exocrine pancreatic insufficiency and its optimal (nutritional) treatment. Even less is known if and to what extent exocrine pancreas insufficiency also affects glycemic control in diabetes. This article aims for summarizing current clinical knowledge on screening, diagnosis, and treatment and gives an overview on the pathophysiology of exocrine pancreatic insufficiency in diabetes. RECENT FINDINGS: Recent studies reveal novel insights into the close interaction of acinar, ductal, and endocrine cells and the gut-pancreas axis. Exocrine pancreatic insufficiency is a clinically relevant, frequent but poorly understood disorder in both type 1 and type 2 diabetes.

Frenotomy for tongue-tie (frenulum linguae breve) showed improved symptoms in the short- and long-term follow-up.

AIM: To evaluate clinical manifestations of tongue-tie as well as short-term and long-term outcomes following frenotomy. METHODS: In this retrospective study, for 329 patients (295 infants and 34 children) who underwent frenotomy between 2011 and 2017, symptoms, short-term and long-term outcomes were evaluated. RESULTS: Of the 295 infants (median age six weeks), 199 (=60%) showed inadequate breastfeeding. Symptoms were painful or sore maternal nipples, poor weight gain, dribbling milk from the corner of the mouth, reduced milk supply, inadequate latch during bottle-feeding and maternal mastitis. In the 34 children, predominant symptoms were articulation disorders, misaligned teeth and problems with swallowing solid food. Of the 141 patients with short-term feedback, 86% reported improvement, 13% an unchanged situation. In a former premature, the reported worsening of symptoms ('breath spells') are likely related to prematurity. Of the 164 patients where the questionnaire for long-term outcome was provided, 82% reported improvement, 16% an unchanged situation. For two infants worsening was reported, referring to refusal to drink from breast or bottle for two hours after the procedure and fever for one day, respectively. CONCLUSION: Frenulum breve is a potential cause of breastfeeding difficulties and can be treated safely and efficiently by frenotomy.

Nitisinone treatment during two pregnancies and breastfeeding in a woman with tyrosinemia type 1 - a case report.

OBJECTIVES: Tyrosinaemia type 1, an inherited disorder of tyrosine metabolism, is usually treated with a tyrosine-defined diet and since 2000 with nitisinone. So far, data about effects of nitisone during pregnancy and breastfeeding are rare. This is the first report of two pregnancies in a patient with tyrosinaemia type 1 while under treatment with nitisinone. CASE PRESENTATION: We here present a 20-year-old female patient with tyrisonemia type 1 receiving treatment with nitisinone and a tyrosine-defined diet since she was diagnosed with tyrosinaemia type 1 at the age of 18 months. During two pregnancies blood concentrations of tyrosine, succinylacetone and nitisinone were measured regularly. Neither infant has tyrosinaemia type 1 and both showed an initial increase in concentrations of tyrosine, succinylacetone and nitisinone. All three metabolites dropped within two weeks after birth. Both were exclusively breastfed for about two weeks. Both children show age-appropriate physical and mental development. CONCLUSIONS: Nitisinone therapy during pregnancy and the short breastfeeding period did not result in adverse events in our patient or her children. Regular assessments of tyrosine, succinylacetone and nitisinone should be made during pregnancy and the breastfeeding period in both the mother and the infant. For better understanding, in principle, all cases of pregnancy and breastfeeding with tyrosinemia type 1 should be assessed and followed to further evaluate the implications of tyrosinaemia type 1 and its treatment during pregnancy. Additionally, even though experience with breastfeeding is limited, medication with nitisinone is safe and there is no reason to consider breastfeeding unsafe or to not recommend it.