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1.
Kidney Int ; 98(6): 1589-1604, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32750457

RESUMO

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.


Assuntos
Anemia , Doenças Renais Policísticas , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Mutação , Doenças Renais Policísticas/genética , Renina/genética , Adulto Jovem
2.
Ann Hum Genet ; 84(1): 80-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31184778

RESUMO

We report on a sibling pair with the EPG5 c.1007A > G mutation who developed a severe form of Vici syndrome and died in infancy. The c.1007A > G (p.Gln336Arg) mutation, affecting the penultimate nucleotide and the splicing of exon 2 is the most common mutation of EPG5 and is typically associated with a less devastating prognosis: cardiomyopathy and cataract are less frequent consequences and the median survival time is 78 months compared to an overall median survival of 42 months. The less severe course related to c.1007A > G was formerly explained by the preserved canonical splicing in 25% of the transcripts. In contrast, we found the messenger RNA encoded by the c.1007A > G allele to be absent, explaining the severe course of the disease. This family provides another example of phenotypic variability related to a differential splicing.


Assuntos
Agenesia do Corpo Caloso/patologia , Proteínas Relacionadas à Autofagia/genética , Catarata/patologia , Mutação , Splicing de RNA , Proteínas de Transporte Vesicular/genética , Adolescente , Agenesia do Corpo Caloso/genética , Catarata/genética , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Irmãos , Taxa de Sobrevida
3.
Orv Hetil ; 158(47): 1864-1867, 2017 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-29153024

RESUMO

Classical galactosemia is an inherited disorder of the carbohydrate metabolism, most often caused by the deficient activity of the enzyme galactose-1-phosphate-uridyltransferase. Classical galactosemia presents in the neonatal period with life threatening illness after galactose is introduced in the diet. Symptoms and signs include poor feeding, vomiting, and diarrhea, weight loss, jaundice, hypotension, cataracts, hepatosplenomegaly, hepatocellular insufficiency, and encephalopathy. Since 1975 the testing for galactosemia is part of the neonatal screening program in Hungary. Affected newborns are recognized in the first days of their life, and special diet is introduced immediately. The therapy of galactosemia is the lactose-free and galactose-poor diet for life. As a result of the nationwide newborn screening and the lifelong medical therapy, early treatment with galactosemia can achieve a normal life without serious complications. Orv Hetil. 2017; 158(47): 1864-1867.


Assuntos
Dieta Saudável , Galactosemias/dietoterapia , Doenças do Recém-Nascido/dietoterapia , Feminino , Galactose/metabolismo , Galactosemias/diagnóstico , Galactosemias/metabolismo , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Masculino
4.
Orv Hetil ; 158(48): 1903-1907, 2017 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-29172660

RESUMO

Inherited errors of metabolism are rare genetic disorders characterized by diverse clinical and biochemical phenotypes. The complexity of signs and symptoms often presents a challenge for both clinicians and laboratory specialists. In many cases, prevention of permanent neurological symptoms or death in patients presenting these disorders is dependent on early diagnosis and introduction of appropriate therapy. For professionals it is indispensable to be familiar with the major clinical signs of inborn errors of metabolism and with the necessary and available laboratory studies to achieve an early diagnosis. The review tries to give a way of approach, diagnostic algorithm of laboratory measurements for the correct diagnosis in inherited errors of metabolism. The combination of biochemical and clinical signs, results of special metabolic investigations represent a portentous challenge in general practice. For the correct diagnosis of an inherited error of metabolism, the teamwork between clinicians and laboratory specialists is indispensable. Orv Hetil. 2017; 158(48): 1903-1907.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , Algoritmos , Técnicas de Laboratório Clínico , Diagnóstico Precoce , Humanos , Recém-Nascido , Comunicação Interdisciplinar , Erros Inatos do Metabolismo/genética
5.
Orv Hetil ; 158(47): 1873-1882, 2017 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-29153022

RESUMO

We report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine- and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood. With the presentation of this case we would like to point out that in the differential diagnosis of recurrent rhabdomyolysis inherited metabolic disorders should be considered regardless of the patient's age. Orv Hetil. 2017; 158(46): 1873-1882.


Assuntos
Rabdomiólise/diagnóstico , Rabdomiólise/metabolismo , Algoritmos , Carnitina/análogos & derivados , Carnitina/análise , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Musculares/diagnóstico
6.
Eur J Pediatr ; 172(5): 623-30, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23319240

RESUMO

UNLABELLED: Smith-Lemli-Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n = 4, clinical score <20) was 0.5-18 years, cholesterol was 2.37 ± 0.8 mmol/L, and 7DHC was 0.38 ± 0.14 mmol/L. In the group of typical SLOS (n = 7, score 20-50), the diagnosis was set up earlier (age of 0.1-7 years); t-cholesterol was 1.47 ± 0.7 mmol/L, and 7DHC was 0.53 ± 0.20 mmol/L. Patients with severe SLOS (n = 4, clinical score > 50) died as newborns and had the lowest t-cholesterol (0.66 ± 0.27 mmol/L), and 7DHC was 0.47 ± 0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p = 0.01), and between the Cho/7DHC ratios of groups (p = 0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p = 0.003) and mild SLOS (p = 0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n = 10) combined with statin therapy (n = 9), increase of aspartate aminotransferase and alanine aminotransferase in 50 % of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended. CONCLUSION: life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.


Assuntos
Colesterol/sangue , Desidrocolesteróis/sangue , Lipoproteínas HDL/sangue , Síndrome de Smith-Lemli-Opitz/diagnóstico , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Hungria , Lactente , Testes de Função Hepática , Masculino , Índice de Gravidade de Doença , Síndrome de Smith-Lemli-Opitz/sangue
7.
Orv Hetil ; 164(47): 1877-1884, 2023 Nov 26.
Artigo em Húngaro | MEDLINE | ID: mdl-38007812

RESUMO

In congenital hyperinsulinemic hypoglycemia - the most common cause of persistent hypoglycemia in infancy - a focal lesion can be identified in 50% of the cases. With appropriate medical care based upon early diagnosis, these patients can be cured by the resection of the lesion rendering unnecessary long time medical care, and avoiding serious brain damage from recurrent hypoglycemic episodes. Genetic testing and 18F-fluoro-dihydroxyphenylalanine PET/CT imaging are essential for determining the best possible treatment. We report 2 cases of focal congenital hyperinsulinism - both male infants: 22 and 2 months of age - treated successfully with enucleation of the pancreas lesion (Semmelweis University, Budapest). Both patients had the pathognomonic mutation of the ABCC8 gene of the ATP-sensitive potassium channel. Radiologic imaging and histology confirmed the diagnosis, and after the operation, pharmacological treatment was terminated in both cases. During the follow-up period (5 and 1.5 years, respectively) they are euglycemic, with no morbidities attributed to the operation. We believe that these two operations for focal hyperinsulinism - diagnosed and localised by the above detailed genetic and specific radiological testing - were the first of their kind in Hungary. Based on the acquired experience, every necessary examination can be achieved in our country to improve patient care, reduce morbidity and medical costs. Orv Hetil. 2023; 164(47): 1877-1884.


Assuntos
Hiperinsulinismo Congênito , Hiperinsulinismo , Lactente , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/cirurgia , Pâncreas/patologia , Mutação , Hiperinsulinismo/patologia
8.
Orv Hetil ; 148(43): 2051-5, 2007 Oct 28.
Artigo em Húngaro | MEDLINE | ID: mdl-17947199

RESUMO

Neonatal lupus erythematosus (NLE) is a disease of the first few months of infancy. It is caused by anti-SSA and anti-SSB antibodies, which are products of maternal autoimmune disorders (SLE, Sjögren, rheumatoid arthritis) and can be passively transported across the placenta. The prevalence of NLE is low. The major clinical findings are cutaneous (typical annular erythematous plaques), cardiac, hepatic and hematologic alterations. Its most severe consequence is third-degree heart block, which is irreversible, requires pacemaker-implantation and responsible for the 20-30% mortality rate. Symptoms usually resolve spontaneously at age of 6-9 months in association with disappearance of maternal antibodies from the infant's serum. In our case the typical cutaneous manifestations covered virtually the whole body, were present at birth, however, no conduction defects developed. The fact that the mother's sickness was not known at birth made it difficult to establish the diagnosis. The significant thrombocytopaenia, progressive skin-changes and the elevated liver function tests necessitated systemic steroid treatment.


Assuntos
Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Sistêmico , Autoanticorpos/sangue , Glucocorticoides/uso terapêutico , Humanos , Recém-Nascido , Testes de Função Hepática , Lúpus Eritematoso Cutâneo/complicações , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Prednisolona/uso terapêutico , Trombocitopenia/etiologia
9.
Pediatrics ; 136(5): e1369-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26504129

RESUMO

Hyperinsulinemic hypoglycemia (HH) is one of the most common causes of persistent hypoglycemic episodes in neonates. Current pharmacologic treatment of neonatal HH includes diazoxide and octreotide, whereas for diffuse, unresponsive cases a subtotal pancreatectomy may be the last resort, with questionable efficacy. Here we report a case of congenital diffuse neonatal HH, first suspected when severe hypoglycemia presented with extremely high serum insulin levels immediately after birth. Functional imaging and genetic tests later confirmed the diagnosis. Failure to respond to a sequence of different treatments and to avoid extensive surgery with predictable morbidity prompted us to introduce a recently suggested alternative therapy with sirolimus, a mammalian target of rapamycin inhibitor. Glucose intake could be reduced gradually while euglycemia was maintained, and we were able to achieve exclusively enteral feeding within 6 weeks. Sirolimus was found to be effective and well tolerated, with no major adverse side effects attributable to its administration.


Assuntos
Hiperinsulinismo/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Sirolimo/uso terapêutico , Humanos , Hiperinsulinismo/complicações , Hipoglicemia/complicações , Recém-Nascido , Masculino , Índice de Gravidade de Doença
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