Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing.

This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended.

Rehabilitation of Post-COVID-19 Musculoskeletal Sequelae in Geriatric Patients: A Case Series Study.

The musculoskeletal system is affected in over 40% of patients with Coronavirus disease 2019 (COVID-19). There is an increased need for post-acute rehabilitation after COVID-19, especially in elderly people with underlying health problems. The aim of this study was to evaluate the benefits of an early and goal-orientated rehabilitation program using combined approaches, robotic medical devices together with other rehabilitation techniques and therapies, in elderly people after acute COVID-19. Ninety-one patients (62.64 ± 14.21 years) previously diagnosed with severe SARS-CoV-2 infection were admitted to the Medical Rehabilitation Clinical Hospital Baile Felix, Romania, for medical rehabilitation, but only six patients (85.33 ± 3.07 years) met the inclusion criteria and participated in the study. The rehabilitation treatment was complex, performed over 4 weeks, and included combined approaches: exercise therapy, robotic gait training, occupational therapy, and massages. Activity and participation evaluation were performed using the Barthel Index and Functional Independence Measure for activities of daily living (ADLs). Assessments were performed at admission and discharge from the rehabilitation clinic. Lokomat patients' reports revealed that the patients had improved motor control (with one exception). The measurement of functional ability revealed an improvement in most cases. This study presents some of the first data on outcomes of COVID-19 patients' musculoskeletal rehabilitation in our country. Early complex medical rehabilitation improved functional independence and autonomy in ADLs in very old patients, post-COVID-19.

Genetic Counseling and Management: The First Study to Report NIPT Findings in a Romanian Population.

Background and Objectives: Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, 13, sex chromosomes aneuploidies and several microdeletions. This study aimed to assess the accuracy of cell free DNA testing based on low-level whole-genome sequencing to screen for these chromosomal abnormalities and to evaluate the clinical performance of NIPT. Materials and Methods: 380 consecutive cases from a single genetic center, from Western Romania were included in this retrospective study. Cell-free nucleic acid extraction from maternal blood, DNA sequencing and analysis of sequenced regions were performed by BGI Hong Kong and Invitae USA to determine the risk of specific fetal chromosomal abnormalities. In high-risk cases the results were checked by direct analysis of fetal cells obtained by invasive methods: 6 chorionic villus sampling and 10 amniocenteses followed by combinations of QF-PCR, karyotyping and aCGH. Results: NIPT results indicated low risk in 95.76% of cases and high risk in 4.23%. Seven aneuploidies and one microdeletion were confirmed, the other results were found to be a false-positive. A gestational age of up to 22 weeks had no influence on fetal fraction. There were no significant differences in fetal fraction across the high and low risk groups. Conclusions: This is the first study in Romania to report the NIPT results. The confirmation rate was higher for autosomal aneuploidies compared to sex chromosome aneuploidies and microdeletions. All cases at risk for trisomy 21 were confirmed. Only one large fetal microdeletion detected by NIPT has been confirmed. False positive NIPT results, not confirmed by invasive methods, led to the decision to continue the pregnancy. The main limitation of the study is the small number of patients included. NIPT can be used as a screening method for all pregnancies, but in high-risk cases, an invasive confirmation test was performed.

Circular RNA-Is the Circle Perfect?

Circular RNA (circRNA) is a distinct class of non-coding RNA produced, in principle, using a back-splicing mechanism, conserved during evolution, with increased stability and a tissue-dependent expression. Circular RNA represents a functional molecule with roles in the regulation of transcription and splicing, microRNA sponge, and the modulation of protein-protein interaction. CircRNAs are involved in essential processes of life such as apoptosis, cell cycle, and proliferation. Due to the regulatory role (upregulation/downregulation) in pathogenic mechanisms of some diseases (including cancer), its potential roles as a biomarker or therapeutic target in these diseases were studied. This review focuses on the importance of circular RNA in cancer.

A Case of Inherited t(4;10)(q26;q26.2) Chromosomal Translocation Elucidated by Multiple Chromosomal and Molecular Analyses. Case Report and Review of the Literature.

We present a complex chromosomal anomaly identified using cytogenetic and molecular methods. The child was diagnosed during the neonatal period with a multiple congenital anomalies syndrome characterized by: flattened occipital region; slight turricephaly; tall and broad forehead; hypertelorism; deep-set eyes; down slanting and short palpebral fissures; epicanthic folds; prominent nose with wide root and bulbous tip; microstomia; micro-retrognathia, large, short philtrum with prominent reliefs; low set, prominent ears; and congenital heart disease. The GTG banding karyotype showed a 46,XY,der(10)(10pter→10q26.2::4q26→4qter) chromosomal formula and his mother presented an apparently balanced reciprocal translocation: 46,XX,t(4;10)(q26;q26.2). The chromosomal anomalies of the child were confirmed by MLPA, and supplementary investigation discovered a quadruplication of the 4q35.2 region. The mother has a triplication of the same chromosomal fragment (4q35.2). Using array-CGH, we described the anomalies completely. Thus, the boy has a 71,057 kb triplication of the 4q26-q35.2 region, a 562 kb microdeletion in the 10q26.3 region, and a 795 kb quadruplication of the 4q35.2 region, while the mother presents a 795 kb triplication of the 4q35.2 region. Analyzing these data, we consider that the boy's phenotype is influenced only by the 4q partial trisomy. We compare our case with similar cases, and we review the literature data.

Morphological Study of Fossa Ovalis in Formalin-Fixed Human Hearts and Its Clinical Importance.

Background and Objectives: Our study aimed to investigate the gross anatomy aspects of the fossa ovalis (FO) and the presence of some anatomical variation resulting from the incomplete fusion of septum primum and septum secundum, such as an atrial septal pouch (SP) and left atrial septal ridge. Materials and Methods: Thirty-one adult human hearts removed from formalin-fixed specimens were examined to provide information about the morphology of the FO. The organs were free of any gross anatomically visible pathological conditions. Results: The most common variants were the FO located in the inferior part of the interatrial septum (64.51%), circular (61.3%), with a net-like structure (51.62%), prominent limbus (93.55%), and patent foramen ovale (PFO) (25.8%). The right SP was observed in 9.67% of specimens, the left SP was observed in 29.03% of cases, and in 51.61% of cases, a double SP was observed. One sample presented a right SP and a double left SP, and one case showed a triple left SP, which was not reported previously to our knowledge. Conclusions: Knowledge of the interatrial septal anatomy becomes important for interventional cardiologists and should be documented before transeptal puncture.

Novel Mutation in APC Gene Associated with Multiple Osteomas in a Family and Review of Genotype-Phenotype Correlations of Extracolonic Manifestations in Gardner Syndrome.

Gardner syndrome is a neoplasic disease that associates intestinal polyposis and colorectal adenocarcinoma with osteomas and soft tissue tumors determined by germline mutations in the APC gene. The early diagnosis and identification of high-risk individuals are important because patients have a 100% risk of colon cancer. We present the case of a family with Gardner syndrome. Cephalometric, panoramic X-rays and CBCT of the proband and her brother showed multiple osteomas affecting the skull bones, mandible and paranasal sinuses. The detailed family history showed an autosomal dominant transmission with the presence of the disease in the mother and maternal grandfather of the proband. Both had the typical signs of disease and died in the fourth decade of life. Based on these aspects the clinical diagnosis was Gardner syndrome. By gene sequencing, a novel pathogenic variant c.4609dup (p.Thr1537Asnfs*7) in heterozygous status was identified in the APC gene in both siblings. We reviewed literature data concerning the correlation between the localization of mutations in the APC gene and the extracolonic manifestations of familial adenomatous polyposis as well as their importance in early diagnosis and adequate oncological survey of patients and families based on abnormal genomic variants.

The Relationship Between Dietary Choices and Health and Premature Vascular Ageing.

The paper aims to review the available data about the main mechanisms enabling improvement or accelerating vascular ageing due to food choices, considering recent experimental and clinical data, and emphasising potential implications for clinical practice and therapy. The main food choices which will be discussed are diets rich in fruits and vegetables, the Mediterranean diet, polyunsaturated fatty acids, cocoa, caffeine, tea, meat, dairy products, sodium, and potassium intake.

Effects of Anthocyanins on Vascular Health.

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.

Bilateral anatomical variations in the extensor compartment of forearm and hand.

An unusual variation of the extensor muscles was found during the routine dissection of the posterior compartment of the forearm. The left forearm presented an extensor medii proprius muscle, the tendon of which had an unusual trajectory. It passed through the second extensor compartment between the tendons of the extensor carpi radialis longus and extensor carpi radialis brevis muscles. The right forearm presented two muscles for the index finger: one, the extensor indicis et medius communis, the tendon of which was split into three tendons, one radial and one ulnar for the index finger and a rudimentary tendon for the middle finger; the second muscle for the index finger had an unusual origin, common with the extensor carpi radialis brevis, and its tendon ran superficially to the tendon of the extensor indicis et medius communis muscle. Knowledge goes tendon variations can be significant not only for clinicians to misdiagnose a debilitating wrist extensor pain syndrome but also for surgeons to avoid iatrogenic injuries in hand surgery.

Heterogeneity in combined immunodeficiencies with associated or syndromic features (Review).

Primary immunodeficiencies are genetic diseases, mainly monogenic, that affect various components of the immune system and stages of the immune response. The category of combined immunodeficiencies with associated or syndromic features comprises over 70 clinical entities, characterized by heterogeneity of clinical presentation, mode of transmission, molecular, biological, mutational and immunological aspects. The mutational spectrum is wide, ranging from structural chromosomal abnormalities to gene mutations. The impact on the function of the proteins encoded by the genes involved is different; loss of function is most common, but situations with gain of function are also described. Most proteins have multiple functions and are components of several protein interaction networks. The pathophysiological mechanisms mainly involve: Missing enzymes, absent or non-functional proteins, abnormal DNA repair pathways, altered signal transduction, developmental arrest in immune differentiation, impairment of cell-to-cell and intracellular communications. Allelic heterogeneity, reduced penetrance and variable expressivity are genetic phenomena that cause diagnostic difficulties, especially since most are rare/very rare diseases, which is equivalent to delaying proper case management. Most primary immunodeficiencies are Mendelian diseases with X-linked or recessive inheritance, and molecular diagnosis allows the identification of family members at risk and the application of appropriate primary and secondary prevention measures in addition to the specific curative ones. In conclusion, recognizing heterogeneity and its sources is extremely important for current medical practice, but also for the theoretical value of improving biological and biomedical applications.

De novo 8p21.3→ p23.3 Duplication With t(4;8)(q35;p21.3) Translocation Associated With Mental Retardation, Autism Spectrum Disorder, and Congenital Heart Defects: Case Report With Literature Review.

Duplications of chromosome 8p lead to rare genetic conditions characterized by variable phenotypes. 8p21 and 8p23 duplications were associated with mental retardation but only 8p23 duplication was associated with heart defects. 8p22→ p21.3 duplications were associated with an autism spectrum disorder in several cases. We present a rare case with a de novo duplication of the entire 8p21.3→ p23.3 region, documented by karyotype, FISH, and array CGH, with t(4;8)(q35;p21.3) translocation in a 7 years-old girl. She was referred for genetic counseling at the age of 20 months due to mild dysmorphic facial features, psychomotor retardation, and a noncyanotic heart defect. Another examination carried out at the age of 5 years, enabled the diagnosis of autism spectrum disorder and attention deficit hyperactivity disorder. Upon re-examination after two years she was diagnosed with autism spectrum disorder, attention deficit hyperactivity disorder, liminal intellect with cognitive disharmony, delay in psychomotor acquisitions, developmental language delay, an instrumental disorder, and motor coordination disorder. Cytogenetic analysis using GTG technique revealed the following karyotype: 46,XX,der(4),t(4;8)(q35;p21.3). The translocation of the duplicated 8pter region to the telomeric region 4q was confirmed by FISH analysis (DJ580L5 probe). Array CGH showed: arr[GRCh37]8p23.3p21.3(125733_22400607) × 3. It identified a terminal duplication, a 22.3 Mb copy number gain of chromosome 8p23.3-p21.3, between 125,733 and 22,400,607. In this case, there is a de novo duplication of a large chromosomal segment, which was translocated to chromosome 4q. Our report provides additional data regarding neuropsychiatric features in chromosome 8p duplication. The phenotypic consequences in our patient allow clinical-cytogenetic correlations and may also reveal candidate genes for the phenotypic features.

CHARGE syndrome associated with de novo (I1460Rfs*15) frameshift mutation of CHD7 gene in a patient with arteria lusoria and horseshoe kidney.

CHARGE syndrome is an autosomal dominant condition caused by mutations in the chromodomain helicase DNA binding protein 7 (CHD7) gene. The present study reported on the case of a 16-month-old female with plurimalformative syndrome, whose etiology was identified by clinical whole-exome sequencing (WES) analysis. Clinical and follow-up assessments identified multiple craniofacial dysmorphisms, congenital defects and functional symptoms, including dysphagia and Marcus Gunn jaw winking synkinesis. Trio-WES analysis was performed for the patient and their parents and the presence of CHARGE syndrome was further indicated using single-molecule real-time sequencing. A de novo pathogenic variant, c.4379_4380del (p.Ile1460Argfs*15), was identified in exon 19 of the CHD7 gene, which resulted in a premature translational stop signal. Trio-WES analysis was used for further investigation, indicating that neither of the patient's parents had the mutation and confirming its de novo nature. To the best of our knowledge, the case of the present study was the first reported case of CHARGE syndrome in Romania with congenital defects including an aberrant right subclavian artery and a horseshoe kidney. CHARGE syndrome was diagnosed in the patient based on the pathogenic mutation in the CHD7 gene. To the best of our knowledge, the present case report is the first to suggest that the CHD7 gene variant is associated with CHARGE syndrome.

Associations between Intrinsic Heart Rate, P Wave and QT Interval Durations and Pulse Wave Analysis in Patients with Hypertension and High Normal Blood Pressure.

The present study aimed to explore the relationship between electrocardiographic (ECG) and pulse wave analysis variables in patients with hypertension (HT) and high normal blood pressure (HNBP). A total of 56 consecutive, middle-aged hypertensive and HNBP patients underwent pulse wave analysis and standard 12-lead ECG. Pulse wave velocity (PWV), heart rate, intrinsic heart rate (IHR), P wave and QT interval durations were as follows: 7.26 ± 0.69 m/s, 69 ± 11 beats/minute, 91 ± 3 beats/minute, 105 ± 22 mm and 409 ± 64 mm, respectively. Significant correlations were obtained between PWV and IHR and P wave duration, respectively, between early vascular aging (EVA) and P wave and QT interval durations, respectively. Linear regression analysis revealed significant associations between ECG and pulse wave analysis variables but multiple regression analysis revealed only IHR as an independent predictor of PWV, even after adjusting for blood pressure variables and therapy. Receiver-operating characteristic (ROC) curve analysis revealed P wave duration (area under curve (AUC) = 0.731; 95% CI: 0.569-0.893) as a predictor of pathological PWV, and P wave and QT interval durations were found as sensitive and specific predictors of EVA. ECG provides information about PWV and EVA in patients with HT and HNBP. IHR and P wave durations are independent predictors of PWV, and P wave and QT interval may predict EVA.

Polyploidy in First and Second Trimester Pregnancies in Romania - a Retrospective Study.

BACKGROUND: Polyploidy is a rare lethal cytogenetic anomaly in pregnancies, generally leading to pregnancy termination. This study aims to compare first and second trimester polyploidy in pregnancies and describe the underlying mechanisms. METHODS: A retrospective study was conducted in three medical genetics laboratories, collecting cases from Eastern, Southern, and Western Romania. The period of interest was January 2008 to December 2018. Prenatal samples (chorionic villi and amniotic fluid) and miscarriage samples were tested by standard karyotyping, as well as QF-PCR or FISH as complementary or alternative techniques. RESULTS: In first trimester pregnancies, we report cytogenetic results of chorionic villi samples from miscarriages: 25 triploid cases and 13 tetraploid cases. In second trimester samples obtained by amniocentesis, cytogenetic findings were positive for 17 triploid cases. Maternal age, age of the pregnancy, and fetal gender identified by ultrasound were recorded in all cases and, additionally, data on biochemical risk and ultrasonographic findings for second trimester pregnancies. CONCLUSIONS: Cytogenetic investigations of spontaneous abortions provide valuable information on the cause of abortion. This information is crucial for genetic counseling and may also contribute to prenatal diagnosis in subsequent pregnancies.

Rare splicing mutation in COL1A1 gene identified by whole exomes sequencing in a patient with osteogenesis imperfecta type I followed by prenatal diagnosis: A case report and review of the literature.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and predisposition to fractures, bone deformities and other major signs such as dentinogenesis imperfecta, blue sclera and deafness. Over 90% of OI cases are caused by mutations in the COL1A1 and COL1A2 genes and the inheritance is autosomal dominant. METHODS: We present a case of a couple requesting genetic counseling, because the man was diagnosed with OI on a clinical and radiological basis and the woman was pregnant. Whole exomes sequencing (WES) was performed in order to identify the mutation (s), followed by prenatal diagnosis. RESULTS: WES identified a rare splicing mutation c.1155 + 1G > C in the COL1A1 gene recognized to be pathogenic and subsequently confirmed by next generation sequencing. The carrier state of the mutation was excluded for the fetus, so the pregnancy was further pursued and a healthy baby was born at term. CONCLUSIONS: WES is a new and effective technique for detecting pathogenic variants in monogenic diseases and it is preferable to use such a technique in diseases with genetic heterogeneity especially when time does not allow another time-consuming diagnostic technique such classical Sanger sequencing. WES offers possibility to expand the global spectrum of OI pathogenic variants enabling the diagnosis of the disease.

A unique case of recurrent fetal cystic hygroma: first fetus with an inherited heteromorphism of chromosome 1 (1qh+) and the second fetus with 69XXX triploidy.

The authors report a unique recurrent septated cystic hygroma (CH), on two successive pregnancies, at five years interval. The chromosome analysis of the first fetus showed an increase in length of heterochromatin on the long arm of chromosome 1 - 1qh+, a chromosomal polymorphism inherited from mother, 46XX,1qh+,14ps+,21ps+. The karyotype of the second CH, with more severe ultrasound (US) imaging, showed a 69XXX triploidy. The patient took no risk and underwent each time a termination of pregnancy (TOP). The first karyotype is generally considered "normal", although there are few reports linking 1qh+ with low fertility, but this was not the case, the patient having, from a previous marriage, a healthy boy and two TOPs. So, this "particular", but "healthy" karyotype was not a cause for the first CH. The second karyotype highlights a possible causality between the 69XXX triploidy, usually associated with partial hydatidiform mole, and a more severe septated CH in the last fetus. Neither the CHs' appearance nor their recurrence seemed to be family linked, as the two CHs had distinct genetic profiles. We recommend that, once CH is diagnosed, a careful US examination is compulsory for the determination of subcutaneous edema, ascites, pleural and pericardial effusions and cardiac or renal abnormalities; an early genetic work-up is mandatory, by chorionic villus sampling or amniocentesis. However, a "healthy" karyotype does not exclude a severe form, as in our first case of CH. Due to the very poor outcome of fetuses with CH, the patient must be thoroughly informed about the short and the long-term fetal prognosis.

Links between High-Sensitivity C-Reactive Protein and Pulse Wave Analysis in Middle-Aged Patients with Hypertension and High Normal Blood Pressure.

Arterial stiffness and arterial age provide valuable prognostic cardiovascular information. The present study aimed at assessing the levels of vitamin D, high-sensitivity C-reactive protein (hsCRP), low-density lipoprotein cholesterol (LDL), and oxidized LDL (oxLDL) in a group of middle-aged hypertensive patients and their relationship with pulse wave velocity (PWV), central blood pressure, and early arterial aging (EAA), respectively. A total of 56 patients, aged 48 ± 6 years, 57% males, with hypertension and high normal blood pressure (HNBP), were investigated using a Mobile-O-Graph, to assess central and peripheral blood pressure, PWV, and arterial age. Additionally, hsCRP, LDL, oxLDL, and 25-hydroxy vitamin D3 were assessed. PWV, 25-hydroxy vitamin D3, hsCRP, oxLDL, and LDL levels were 7.26 ± 0.69 m/s, 25.99 ± 11.17 microg/l, 0.48 ± 0.44 mg/dl, 261.37 ± 421 ng/ml, and 145.73 ± 39.53 mg/dl, respectively. Significant correlations were obtained between oxLDL and pulse pressure amplification (rS = -0.347, p = 0.028) and between hsCRP and LDL levels with PWV and EAA, respectively. ROC curve analysis revealed that hsCRP is a sensitive and specific predictor of EAA and increased PWV values. Concluding, vitamin D deficiency and increased hsCRP and LDL values are very common, and high oxidized LDL is related to pulse pressure amplification in patients with elevated blood pressure. Vitamin D level and high-sensitivity C-reactive protein and LDL provide valuable information in middle-aged hypertensive and HNBP patients related to arterial stiffness and early arterial aging, but only hsCRP is a sensitive predictor of EAA and PWV.

Incidence and Spectrum of Chromosome Abnormalities in Miscarriage Samples: A Retrospective Study of 330 Cases.

Embryonic chromosome abnormalities are the most important causes of early spontaneous abortions. The aim of this study was to evaluate the spectrum and the frequencies of chromosomal anomalies in spontaneous miscarriages and to correlate these with maternal and gestational age. A retrospective study was conducted based on data obtained from a single medical genetics laboratory that collects cases from Western Romania. Long-term cultures of chorionic villus samples were established for karyotype analysis by GTG banding. Additionally, we performed QF-PCR to detect aneuploidies for chromosomes 13, 18, 21, X, and Y. In total, chorionic villi samples of 330 miscarriages (from August 2007 to November 2018) were analyzed. Results were obtained for 90.6% (299/330) of the cases. The remaining 9.4% (31/330) were excluded from evaluation due to inconclusive results. An abnormal karyotype was found in 156 cases (47.27%), while in 143 cases (43.33%) a normal karyotype was present. Of the abnormal cases, 88 (56.4%) had trisomies, 25 (16.0%) presented polyploidies, 25 (16.0%) had monosomy X, and 19 (11.5%) chromosome rearrangements. QF-PCR analysis identified aneuploidy in 2 out of 8 samples (25%). Cytogenetic investigations of spontaneous abortions provide valid data as to the cause of the abortion. This information may also be helpful for genetic counseling and considering future pregnancies.

Clinical and genetic diversity of congenital hyperammonemia.

Congenital hyperammonemia (HA) due to inborn errors of metabolism is a rare condition with a high rate of mortality. The main effects occur at the central nervous system (CNS) level, being neurotoxic by alteration of the neurotransmitter function. HA can be triggered by an inappropriate diet, infection or stress, but can also occur without a precise cause. In cases of metabolic crises, patients require immediately intensive care. In the last seven years (2011-2017), we cared in the Department of Genetics, "Dr. Gavril Curteanu" Municipal Clinical Hospital, Oradea, Romania, six patients with different causes of congenital HA: one case with argininosuccinate lyase deficiency, two cases (brothers) with argininosuccinate synthase deficiency, one case with non-ketotic hyperglycinemia, one case hyperglycinemia and one case with HA with unknown etiology. The medical surveillance and care of these children over a long period of time raise serious problems for the family and society. These patients are dependent on medical services: qualified medical staff (pediatrician, geneticist, radiologist, biochemist, nutritionist, and psychologist), expensive and repeated medical investigations, prolonged and costly medication. Most of these costs could be avoided by early diagnosis and treatment, rigorous monitoring of HA, ensuring proper diet and medication. Our experience regarding the clinical and genetic particularities of patients with congenital HA could be an opportunity for the better knowledge of special needs of these patients, especially regarding the psychological and social aspects.