scholarly journals Case Report: Extended Clinical Spectrum of the Neonatal Diabetes With Congenital Hypothyroidism Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Vera Splittstoesser ◽  
Heike Vollbach ◽  
Michaela Plamper ◽  
Werner Garbe ◽  
Elisa De Franco ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Causal Relation ◽  
Phenotypic Variability ◽  
Pancreatic Insufficiency ◽  
Pancreatic Enzyme ◽  
Neonatal Diabetes ◽  
Homozygous Deletion ◽  
Clinical Aspects ◽  
Compound Heterozygous ◽  
Antioxidative Vitamins

BackgroundNeonatal diabetes with congenital hypothyroidism (NDH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLI-similar 3 coding gene GLIS3. Almost 20 patients have been reported to date, with significant phenotypic variability.Case presentationWe describe a boy with a homozygous deletion (exons 5-9) in the GLIS3 gene, who presents novel clinical aspects not reported previously. In addition to neonatal diabetes, congenital hypothyroidism and other known multi-organ manifestations such as cholestasis and renal cysts, he suffered from hyporegenerative anemia during the first four months of life and presents megalocornea in the absence of elevated intraocular pressure. Compensation of partial exocrine pancreatic insufficiency and deficiencies in antioxidative vitamins seemed to have exerted marked beneficial impact on several disease symptoms including cholestasis and TSH resistance, although a causal relation is difficult to prove. Considering reports on persistent fetal hemoglobin detected in a few children with GLIS3 mutations, the transient anemia seen in our patient may represent a further symptom associated with either the GLIS3 defect itself or, secondarily, micronutrient deficiency related to exocrine pancreatic deficiency or cholestasis.ConclusionsOur report expands the phenotypic spectrum of patients with GLIS3 mutations and adds important information on the clinical course, highlighting the possible beneficial effects of pancreatic enzyme and antioxidative vitamin substitutions on characteristic NDH syndrome manifestations such as TSH resistance and cholestasis. We recommend to carefully screen infants with GLIS3 mutations for subtle biochemical signs of partial exocrine pancreatic deficiency or to discuss exploratory administration of pancreatic enzymes and antioxidative vitamins, even in case of good weight gain and fecal elastase concentrations in the low-to-normal range.

scholarly journals Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20) in the Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic Fibrosis

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Michael W. Konstan ◽  
Theodore G. Liou ◽  
Steven D. Strausbaugh ◽  
Richard Ahrens ◽  
Jamshed F. Kanga ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Pancreatic Enzyme ◽  
Gastrointestinal Symptoms ◽  
Signs And Symptoms ◽  
Exocrine Pancreatic Insufficiency ◽  
Efficacy And Safety ◽  
Protein Nitrogen ◽  
Enzyme Replacement ◽  
New Formulation

Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI).Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms.Methods. Patients (n=31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared.Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp.,P<.0001for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE.Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.

Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism

Thyroid ◽  
2019 ◽  
Vol 29 (7) ◽  
pp. 1023-1026 ◽  
Author(s):  
Mariano Martín ◽  
Carlos Eduardo Bernal Barquero ◽  
Romina Celeste Geysels ◽  
Patricia Papendieck ◽  
Victoria Peyret ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Compound Heterozygous ◽  
Sodium Iodide Symporter ◽  
Pathogenic Variants

scholarly journals Fatal Neonatal DOLK-CDG as a Rare Form of Syndromic Ichthyosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Katalin Komlosi ◽  
Olivier Claris ◽  
Sophie Collardeau-Frachon ◽  
Julia Kopp ◽  
Ingrid Hausser ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Heart Tissue ◽  
Organ Involvement ◽  
Compound Heterozygous ◽  
Diagnostic Challenge ◽  
Second Child ◽  
Dilatative Cardiomyopathy ◽  
Collodion Baby ◽  
Fatal Course ◽  
Compound Heterozygous Variants

Neonatal collodion baby or ichthyosis can pose a diagnostic challenge, and in many cases, only additional organ involvement or the course of the disease will help differentiate between non-syndromic and syndromic forms. Skin abnormalities are described in about 20% of the congenital disorders of glycosylation (CDG). Among those, some rare CDG forms constitute a special group among the syndromic ichthyoses and can initially misdirect the diagnosis towards non-syndromic genodermatosis. DOLK-CDG is such a rare subtype, resulting from a defect in dolichol kinase, in which the congenital skin phenotype (often ichthyosis) is later associated with variable extracutaneous features such as dilatative cardiomyopathy, epilepsy, microcephaly, visual impairment, and hypoglycemia and may lead to a fatal course. We report two neonatal cases of lethal ichthyosis from the same family, with distal digital constrictions and a progressive course leading to multi-organ failure and death. Postmortem trio whole-exome sequencing revealed the compound heterozygous variants NM_014908.3: c.1342G&gt;A, p.(Gly448Arg) and NM_014908.3: c.1558A&gt;G, p.(Thr520Ala) in the DOLK gene in the first affected child, which were confirmed in the affected sibling. Reduced staining with anti-α-Dystroglycan antibody was observed in frozen heart tissue of the second child as an expression of reduced O-mannosylation due to the dolichol kinase deficiency. In addition to the detailed dermatopathological changes, both cases presented hepatic and extrahepatic hemosiderosis on histological examination. Our patients represent an early and fatal form of DOLK-CDG with a striking presentation at birth resembling severe collodion baby. Both cases emphasize the phenotypic variability of glycosylation disorders and the importance to broaden the differential diagnosis of ichthyosis and to actively search for organ involvement in neonates with ichthyosis.

scholarly journals Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaona Luo ◽  
Chunmei Wang ◽  
Longlong Lin ◽  
Fang Yuan ◽  
Simei Wang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Neuromuscular Junctions ◽  
Three Dimensional ◽  
Missense Variant ◽  
Homozygous Deletion ◽  
Dimensional Structure ◽  
Compound Heterozygous ◽  
Splicing Mutation ◽  
Gene Encoding ◽  
Congenital Myasthenia

The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G&gt;A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A&gt;C (p.Q381P). The splicing mutation c.393+1G&gt;A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A&gt;C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14–15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G&gt;A, missense mutation c.1A&gt;C (p.Q381P), and COLQ exon 14–15 deletion could cause CMS.

scholarly journals Coefficients of Fat and Nitrogen Absorption in Healthy Subjects and Individuals with Cystic Fibrosis

2007 ◽  
Vol 12 (1) ◽  
pp. 47-52
Author(s):  
Drucy Borowitz ◽  
Michael W. Konstan ◽  
Anna O'Rourke ◽  
Morty Cohen ◽  
Leslie Hendeles ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Subjects ◽  
Pancreatic Insufficiency ◽  
Pancreatic Enzyme ◽  
High Protein Diet ◽  
Fat Absorption ◽  
Nitrogen Absorption ◽  
High Fat ◽  
Food Dye ◽  
Median Test

BACKGROUND We sought to compare the differences of coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) in healthy individuals and those with cystic fibrosis (CF) and to study the precision of CFA and CNA. METHODS Sixteen healthy and 23 subjects with CF and pancreatic insufficiency ate a high-fat, high-protein diet for 72 hours; stool was collected between blue food dye markers to determine CFA and CNA. Subjects with CF withheld pancreatic enzymes. Tests were repeated on 5 of the CF and 10 of the healthy subjects. RESULTS In healthy subjects, mean CFA was 93.5% ± 2.7%; mean CNA was 88.1% ± 5%. Median test-retest in 10 healthy subjects was +0.7% CFA (range, −8.1% to + 5.9%) and +0.9% CNA (range, −14.6% to +6.8%). For subjects with CF, mean CFA was 38.5% ± 14.7% and mean CNA was 52.2% ± 11.4%. Median test-retest change in 5 subjects with CF was −6.9% CFA (range, −19.7% to +42.8%) and +14.7% CNA (range, −6.4% to +42.8%). CONCLUSIONS CFA and CNA have inconsistent precision in CF. The limitations of CFA as a measure of steatorrhea correction in CF should be recognized in studies of pancreatic enzyme supplements.

scholarly journals The role of nutrition and pancreatic enzyme replacement therapy in children with cystic fibrosis

2021 ◽  
Vol 4 (2) ◽  
pp. 84-93
Author(s):  
Muzal Kadim ◽  
William Cheng
Keyword(s):  
Cystic Fibrosis ◽  
Nutritional Status ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pancreatic Insufficiency ◽  
Pancreatic Enzyme ◽  
Nutritional Intervention ◽  
Enzyme Replacement ◽  
Pancreatic Enzyme Replacement Therapy

Background Cystic fibrosis (CF) is an inherited genetic disorder with high mortality and morbidity. CF is strongly correlated with malnutrition due to higher energy losses, pancreatic insufficiency, chronic inflammation, higher resting energy expenditure, and feeding problems. Malnutrition in CF patients associated with worse survival. Thus, appropriate and prompt nutritional intervention should be addressed to reduced malnutrition in CF patients. Methods The literature search was performed on 9 August 2021 in four major databases such as MEDLINE, EBSCOhost, Cochrane Reviews, and Web of Sciences to find the role of nutrition and pancreatic enzyme replacement therapy in pediatrics population with cystic fibrosis. Recent findings In recent decades, early nutritional management and pancreatic enzyme replacement therapy (PERT) have been shown to improve CF patient’s outcomes. Nutrition should be given in higher calories compared to healthy individuals with close and regular nutritional status monitoring. High protein and fat diets are essential for CF patient’s overall survival. Adequate level of micronutrients should be ensured to avoid morbidity caused by micronutrients deficiency. Regular pancreatic insufficiency screening should be done annually in order to start PERT early.  Further research focusing on body composition, growth chart, protein intake, and PERT are needed to further improve the management of CF patient. Conclusion Nutritional intervention and PERT play an important role in prolonging CF patient survival. Both treatments should be initiated early with nutritional status close monitoring and tailored to each individual. Collaboration with parents and children is critical to warrant that CF patients followed the dietary advice.

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