A Lithuanian Case of Tyrosinemia Type 1 with a Literature Review: A Rare Cause of Acute Liver Failure in Childhood.

Hereditary type 1 tyrosinemia (HT1) is a rare inherited autosomal recessive disorder of tyrosine metabolism, characterized by progressive liver damage, dysfunction of kidney tubules, and neurological crises. In the course of this disease, due to the deficiency of the enzyme fumarylacetoacetate hydrolase (FAH), toxic intermediate metabolites of tyrosine breakdown, such as fumarylacetoacetate (FAA), succinylacetoacetate (SAA), and succinylacetone (SA), accumulate in liver and kidney cells, causing cellular damage. Because of this, an increased SA concentration in the blood or urine is pathognomonic of HT1. In the year 2000, HT1 was diagnosed in Lithuania for the first time, and this was the first time when a specific treatment for HT1 was administered in the country. Over two decades, four cases of this disease have been diagnosed in Lithuania. In the first of these patients, the disease was diagnosed in infancy, manifesting as liver damage with liver failure. Treatment with nitisinone was initiated, which continues to be administered, maintaining normal liver function. Liver transplantation was performed on two subsequent patients due to complications of HT1. It is crucial to diagnose HT1 as early as possible in order to reduce or completely eliminate complications related to the disease, including progressive liver failure and kidney dysfunction, among others. This can only be achieved by conducting a universal newborn screening for tyrosinemia and by starting treatment with nitisinone (NTBC) before the age of 1 month in all cases of HT1. However, in those countries where this screening is not being carried out, physicians must be aware of and consider this highly rare disorder. They should be vigilant, paying attention to even minimal changes in a few specific laboratory test results-such as unexplained anemia alongside neutropenia and thrombocytopenia-and should conduct more detailed examinations to determine the causes of these changes. In this article, we present the latest clinical case of HT1 in Lithuania, diagnosed at the Children's Diseases' Clinic of the Lithuanian University of Health Sciences (LUHS) Hospital Kaunas Clinics. The case manifested as life-threatening acute liver failure in early childhood. This article explores and discusses the peculiarities of diagnosing this condition in the absence of universal newborn screening for tyrosinemia in the country, as well as the course, treatment, and ongoing monitoring of patients with this disorder.

Two Lithuanian Cases of Classical Galactosemia with a Literature Review: A Novel GALT Gene Mutation Identified.

Galactosemia is a rare autosomal recessive genetic disorder that causes impaired metabolism of the carbohydrate galactose. This leads to severe liver and kidney insufficiency, central nervous system damage and long-term complications in newborns. We present two clinical cases of classical galactosemia diagnosed at the Lithuanian University of Health Sciences (LUHS) Kaunas Clinics hospital and we compare these cases in terms of clinical symptoms and genetic variation in the GALT gene. The main clinical symptoms were jaundice and hepatomegaly, significant weight loss, and lethargy. The clinical presentation of the disease in Patient 1 was more severe than that in Patient 2 due to liver failure and E. coli-induced sepsis. A novel, likely pathogenic GALT variant NM_000155.4:c.305T>C (p.Leu102Pro) was identified and we believe it could be responsible for a more severe course of the disease, although further study is needed to confirm this. It is very important to suspect and diagnose galactosemia as early in its course as possible, and introduce lactose-free formula into the patient's diet. Wide-scale newborn screening and genetic testing are particularly crucial for the early detection of the disease.

Significance of dietotherapy on the clinical course of atopic dermatitis.

UNLABELLED: The aim of this study was to determine the efficiency of individual balanced replacement diet in treatment of children with atopic dermatitis, to compare the course of atopic dermatitis and gastrointestinal disorders, as well as the data of skin patch test after a one-year period of dietary treatment. PATIENTS AND METHODS: The study group included 154 children (their age varied from 6 months to 18 years) with atopic dermatitis, for whom food allergens were determined by allergic skin tests (skin prick and patch). These children were recommended an individual balanced replacement diet, where possible food allergens were replaced by other products that do not cause allergic reactions. After a one-year dietary treatment, 109 (70.8%) children (such number came for the second study) were tested repeatedly. The following aspects were evaluated for all these children: clinical course of atopic dermatitis (children's mothers provided answers about exacerbation of allergic rash during the last 12 months, gastrointestinal disorders, and used medicines), severity of the progress of atopic dermatitis (SCORAD index). Besides, skin patch test with 25 food allergens was carried out. RESULTS: Children who followed dietary recommendations were younger than children who failed to follow dietary recommendations because of a variety of reasons (P=0.01). Even 49 (62.8%) patients who followed dietary recommendations have shown the following results during the second test: allergic rash disappeared and they did not have to take medicines against allergy anymore. Patients who followed their individual dietary recommendations more rarely suffered from severe allergic rash problems during a 12-month period (P=0.01) and they had to take fewer medicines against allergy, compared to children who did not follow their dietary recommendations (P=0.001). Clinical course of atopic dermatitis in children who followed individual dietary recommendations was easier compared to children who did not follow such recommendations (P=0.001). During a one-year dietary treatment, 28.2% of children with atopic dermatitis became more tolerant to earlier food allergens. After the comparison of skin patch test results (before dietary treatment and after a one-year period), it was determined that only skin patch tests against buckwheat, oat, beef, and cacao did not change statistically significantly. Results of skin patch tests against other food products were found to be positive more rarely. Besides, children who followed their dietary recommendations suffered from gastrointestinal disorders more rarely as compared to children who did not follow their dietary recommendations (P=0.01). They suffered less from abdominal pain (P=0.01), abdominal distention (P=0.044), and constipation (P=0.035). CONCLUSIONS: Individual balanced replacement diet for children with atopic dermatitis helped to fully control nutrition of sick children from various age groups and had a positive effect on the clinical course of atopic dermatitis. Patients who followed their individual dietary recommendations suffered from severe allergic rash more rarely and they had to take fewer medicines against allergy as compared to children who did not follow dietary recommendations. Clinical course of atopic dermatitis in children who followed individual dietary recommendations was easier as compared to children who did not follow such recommendations. One-third of children with atopic dermatitis became more tolerant to earlier food allergens during a one-year period. After a one-year dietotherapy treatment, positive patch test reactions to many food products appeared to be more rarely, except for buckwheat, oat, beef, and cacao. Besides, children who followed their dietary recommendations suffered from gastrointestinal disorders (abdominal pain, abdominal distention, and constipation) significantly more rarely as compared to children who did not follow their dietary recommendations.

[Relevance of examination and treatment of the most common gastrointestinal disorders in children in Lithuania during the last decade]. / Dazniausiu vaiku virskinimo sistemos sutrikimu tyrimo ir gydymo aktualijos Lietuvoje per pastaraji desimtmeti.

In the last decade, scientific studies in the field of children's gastroenterology performed in Lithuania explored different problems: pathology of Helicobacter pylori infection and food allergy. Our studies revealed that children with atopic dermatitis had gastrointestinal complaints (abdominal pain, diarrhea, distension and unstable stool, which appeared with the exacerbation of skin rash) more often as compared to nonallergic children of the control group. Abdominal pain in children with atopic dermatitis with local rash was more frequent and lasted longer than in control group children, whereas children with extended rash had stools more frequently. Gastrointestinal disorders in children with atopic dermatitis statistically significantly did not depend on the extent of skin rash and severity of atopic dermatitis. In our scientific research on the importance of H. pylori infection on children's gastrointestinal system, children with chronic dyspepsia were examined. Endoscopy, rapid urease test, biopsies from antrum and corpus of stomach and their histological examination as well as serologic tests were done. According to the results obtained, we recommend to examine children with chronic dyspepsia in a complex way: not only endoscopic examination, but H. pylori diagnostic tests should be performed as well. Serologic test is not suitable for screening H. pylori infection in children. Considering this, we recommend to use no fewer than two different methods to diagnose this infection. The highest frequency of H. pylori infection was found in children with duodenal ulcer; histological changes in their gastric pylorus and corpus mucosa were greatest. More than half of children with nonulcer dyspepsia were infected with H. pylori. After eradication of H. pylori infection, the prevalence of dyspepsia in children with duodenal ulcer decreased.

Gastrointestinal disorders in children with atopic dermatitis.

UNLABELLED: The aims of this study were to analyze the peculiarities of allergies to food; to determine gastrointestinal disorders, endoscopic signs of mucosal damage and histological lesions of the mucosa and to establish their relation to the extent of atopic dermatitis and its degree of severity. MATERIAL AND METHODS: A total of 164 children (86 boys and 78 girls) suffering only from atopic dermatitis were examined. Atopic dermatitis was diagnosed using standard diagnostic criteria; extent of disease (the Basic Clinical Scoring System (BCSS)) and the severity (Scoring Atopic Dermatitis (SCORAD) index), total serum IgE levels were determined; skin prick and patch tests with the main food allergens were performed. Using questionnaire gastrointestinal disorders with the symptoms of atopic dermatitis were ascertained. In children with atopic dermatitis suffering from chronic dyspepsia esophagealgastroduodenoscopy was performed and biopsy samples from the antrum of the stomach and duodenum were taken. RESULTS: The age of patients ranged from 6 months to 18 years. According to extent of atopic dermatitis and degree of severity localized, mild atopic dermatitis prevailed. Analysis of the changes in total Ig E levels showed different degree of sensitization of the children examined. Considering the type of allergic reaction, immediate-type allergic reactions dominated only in 11.6% of children with atopic dermatitis, whereas delayed-type allergic reactions manifested in 44.5% of children. No food allergy was present in one-fifth of children with atopic dermatitis. One hundred four (63.4%) children complained of gastrointestinal disorders. Of these 104 patients, 17 children (mean age 6.9 years) who underwent esophagealgastroduodenoscopy with biopsy had no pathology; however, histological examination of mucosa revealed eosinophilic infiltration in the gastric antrum and duodenum in three children. CONCLUSIONS: The most common gastrointestinal disorders are: abdominal pain vomiting, diarrhea, abdominal distention, and constipation. The incidence of gastrointestinal disorders does not depend on the extent and severity of atopic dermatitis. Gastrointestinal disorders manifest independent of the type of allergic reactions inducing atopic dermatitis. The most common food allergens, such as soy, milk, peanuts, corn, carrots, rye, wheat, white of the egg, cod, and chicken were determined by skin patch test. According to our data, no pathology was found in children with atopic dermatitis during endoscopic examination. Our data showed that allergic-like changes in gastric and duodenal mucosa were present only in older (7-10-year-old) children.

Role of the skin patch test in diagnosing food allergy in children with atopic dermatitis.

UNLABELLED: The aim of the study was to determine peculiarities of food allergy in children with atopic dermatitis and to evaluate the significance of skin patch test in determining the main food allergens. METHODS: One hundred and eight children (57 boys and 51 girls) with atopic dermatitis were examined. Atopic dermatitis was diagnosed by standard diagnostic criteria, severity of the progress of the disease was determined using SCORAD index and the amount of total IgE in blood, skin prick and patch tests with the main food allergens were performed. RESULTS: The age of the patients varied from 6 months to 16 years, however, almost half (41%) of them were toddlers (1-3 years old). Mild form of atopic dermatitis was dominating (52%). Analysis of the total IgE amount in blood showed different degree of sensitivity of the children tested. Normal amount of the total IgE in blood was found in 73.1% of children with atopic dermatitis, and the increased total IgE amount was found only in 26.9% of children. Positive skin prick test with the standard and the most common food allergens was found only in 4.63% of children with atopic dermatitis, while the positive skin patch test with 25 food allergens was found in 68.5% of children. Depending on the type of the allergic reaction, immediate type reaction dominated only in 10.3% of children with atopic dermatitis, while the delayed type allergic reactions were characteristic to food allergies in 48.3% of children with atopic dermatitis. Food allergy was not found in one fifth of children with atopic dermatitis. CONCLUSIONS: Skin patch test is an informative and reliable diagnostic test in evaluating the delayed type allergic reactions. In about half of the tested persons with atopic dermatitis, food allergy appeared in delayed type allergic reactions. Therefore it is very important to do the skin patch test for toddlers and pre-school age children. The most common allergens found with the help of skin patch test are soy, milk, peanuts, carrot, egg whites, wheat, and corn.