Genetic testing is necessary for correct diagnosis and treatment in patients with isolated methylmalonic aciduria: a case report.

Background: Isolated methylmalonic aciduria can be caused by pathogenic mutations in the gene for methylmalonyl-CoA mutase or in the genes encoding enzymes involved in the intracellular metabolism of cobalamin. Some of these mutations may be cobalamin responsive. The type of methylmalonic aciduria cannot always be assumed from clinical manifestation and the responsiveness to cobalamin has to be assessed for appropriate cobalamin administration, or to avoid unnecessary treatment.

A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.

Congenital disorder of glycosylation type Ig (ALG12-CDG) is a rare inherited metabolic disease caused by a defect in alpha-mannosyltransferase 8, encoded by the ALG12 gene (22q13.33). To date, only 15 patients have been diagnosed with ALG12-CDG globally.

Congenital disorders of glycosylation - an umbrella term for rapidly expanding group of rare genetic metabolic disorders - importance of physical investigation.

Aim: Congenital disorders of glycosylation (CDG) belong to an expanding group of rare genetic metabolic disorders caused by defects in the complex chemical enzymatic process of glycosylation. The study is aimed at presenting a case report of a premature dysmorphic newborn, clinical presentation of the condition, the way it was diagnosed and treated, as well as its comparison with the known cases.

Results: The result of glycan analysis supports the assumption of a supposed glycosylation disorder and also specifies a specific subtype: CDG-1, subtype ALG12-CDG (Ig).

SLC37A4-CDG: Mislocalization of the glucose-6-phosphate transporter to the Golgi causes a new congenital disorder of glycosylation.

Loss-of-function of the glucose-6-phosphate transporter is caused by biallelic mutations in SLC37A4 and leads to glycogen storage disease Ib. Here we describe a second disease caused by a single dominant mutation in the same gene. The mutation abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal.

Ophthalmological finding in a patient with lowe syndrome.

The authors present the ophthamological finding in a patient who at the age of 4.5 months was admitted due to a finding of total bilateral congenital cataract. The patient was observed by a neurologist for central hypotonia and mental retardation.

Intrathecal baclofen in mucopolysaccharidosis type II (Hunter syndrome): case report.

Purpose: Intrathecal baclofen administration is commonly used in the treatment of children's spasticity. In general, candidates for baclofen pump are patients with spastic form of cerebral palsy. Intrathecal baclofen in the treatment of spasticity due to a metabolic disorder is rarely reported.

Congenital hyperinsulinism and glycogenosis-like phenotype due to a novel HNF4A mutation.

Aim: Congenital hyperinsulinism (CHI) and glycogen storage disease (glycogenosis) are both causing hypoglycemia during infancy, but with different additional clinical features and therapeutic approach. We aimed to identify a genetic cause in a child with an ambiguous phenotype.

Methods And Results: We present a child with hyperinsulinemic hypoglycemia, physiological 3-OH butyrate, increased triglyceride serum levels, increased level of glycogen in erythrocytes, increased liver transaminases, and increased echogenicity on liver ultrasonography.

The significance of electron microscopic examination of gingiva in cases of Hunter syndrome and hereditary gingival fibromatosis.

Introduction: Electron microscopy has been for decades a basic morphological method still used in diagnostic protocols of some pathological conditions affecting the ultrastructure of cells and extracellular matrix. The aim of this study was an ultrastructural description of gingiva of patients with Hunter syndrome and hereditary gingival fibromatosis.

Patients And Methods: Gingival biopsies were obtained during surgical periodontal treatment from a 9-year-old boy with Hunter disease (with enzyme replacement therapy with recombinant human idursulphase) and a 15-year-old girl with hereditary gingival fibromatosis.

GAI - distinct genotype and phenotype characteristics in reported Slovak patients.

Objectives: The clinical, biochemical and genetic findings in two Slovak patients with glutaric aciduria type I (GAI) are presented.

Background: GAI is a rare autosomal recessive neuro-metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase, which is involved in the catabolic pathways of lysine, hydroxylysine and tryptophan. This enzymatic defect gives rise to elevated levels of glutaric acid (GA), 3-hydroxyglutaric acid (3-OH-GA) and glutarylcarnitine (C5DC) in body fluids.

Genotype-phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (Hunter syndrome, MPS II, OMIM 309900) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (IDS). We analyzed clinical and laboratory data from 44 Slavic patients with this disease. In total, 21 Czech, 7 Slovak, 9 Croatian and 7 Serbian patients (43 M/1 F) were included in the study (median age 11.

TMEM70 deficiency: long-term outcome of 48 patients.

Objectives: TMEM70 deficiency is the most common nuclear-encoded defect affecting the ATP synthase. In this multicentre retrospective study we characterise the natural history of the disease, treatment and outcome in 48 patients with mutations in TMEM70. Eleven centers from eight European countries, Turkey and Israel participated.

Lack of association between peripheral activity of thyroid hormones and elevated TSH levels in childhood obesity.

Objective: An elevated thyroid stimulating hormone (TSH) level is a frequent finding in obese children, but its association with peripheral hormone metabolism is not fully understood. We hypothesized that in obesity, the changes in thyroid hormone metabolism in peripheral tissues might lead to dysregulation in the thyroid axis. The purpose of this study was to investigate the association of TSH with thyroid hormones in a group of obese children as compared to normal-weight controls.

[Historical aspects of the Smith-Lemli-Opitz syndrome].

The new malformation syndrome was first described approximately 50 years ago in three unrelated patients in Department of Pediatrics at the University of Wisconsin, Madison, (Smith, Lemli, Opitz 1964). This syndrome was called RSH syndrome after the first 3 patients studied. First Slovak patient with phenotypic features of this new syndrome was described by professor Sršeň in 1972.

Newborn with neonatal form of molybdenum cofactor deficiency - the first patient in the Slovak Republic.

Objective: To present the case of a term newborn with rapid progression of signs of neurodegenerative disease.

Results: In a case of a term newborn with numerous dysmorphic features, with seizure activity from the 3rd day of life, hypertonia and serious changes on brain parenchyma were presented. Diagnosis of molybdenum cofactor deficiency was confirmed by the decreased level of uric acid, 31 μmol/l, in serum, increased excretion of thiosulfate and S-sulfocysteine in urine, taurine (1729.

Conjugated hyperbilirubinaemia as the first manifestation of mevalonic aciduria in a term newborn.

Objectives: To present clinical and laboratory findings in the case of a term newborn with conjugated hyperbilirubinaemia and to stress the importance of differential diagnosis.

Results: A term newborn delivered by caesarean section (birth weight 2550 g, birth length 47 cm, value of Apgar score 9/10) with good direct adaptation had on the first day of life increased levels of conjugated bilirubin (23 micromol/l), unconjugated bilirubin (55 micromol/l) and C-reactive protein 39.4 g/l.

Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease.

Purpose: Fabry disease, a genetic deficiency of alpha-galactosidase A, is characterized by pathogenic cellular accumulation of globotriaosylceramide. During clinical trials, recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme, Genzyme Corporation, Cambridge, MA), infused intravenously at 1.0 mg/kg every 2 weeks for 6 months, cleared or reduced globotriaosylceramide in renal, cardiac, and dermal microvascular endothelia and other cells, with results sustained for up to 5 years in most patients evaluated.

Reversible asphyxial status in a newborn due to neonatal form of carnitine palmitoyltransferase II deficiency.

Objectives: To present a term newborn with severe asphyxial status due to dysrrhythmia induced by the neonatal form of carnitine palmitoyltransferase II deficiency (CPT II).

Results: Term newborn delivered spontaneously (birth weight 3450 grams, birth length 52 cm, values of Apgar score 10/10) with good direct adaptation, on second day of life he manifested severe asphyxial status followed by cardiorespiratory insufficiency with circulatory failure. After prolonged resuscitation of 3 hours, the child was admitted to our neonatological department.

Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms.

Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females, is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Here we report mutation analysis of the MECP2 gene in 87 patients with RTT from the Czech and Slovak Republics, and Ukraine. The patients, all girls, with classical RTT were investigated for mutations using bi-directional DNA sequencing and conformation sensitive gel electrophoresis analysis of the coding sequence and exon/intron boundaries of the MECP2 gene.

Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms. NKH is caused by deficiency of the glycine cleavage multi-enzyme system with three specific components encoded by GLDC, AMT, and GCSH. We undertook the first comprehensive screening for GLDC, AMT, and GCSH mutations in 69 families (56, six, and seven families with neonatal, infantile, and late-onset type NKH, respectively).