Hereditary Metabolic Diseases Research Articles

Neuropathology II: diseases of the central and peripheral nervous systems : Outlook on new techniques in electron microscopy

In the diagnosis of diseases of the central and peripheral nervous systems, the use of electron microscopic analyses has become rare these days. However, there are questions in which the method is helpful in confirming the etiopathogenesis of the disease. Hereditary neurodegenerative and metabolic diseases, such as the lysosomal storage disease neuronal ceroid lipofuscinosis, are associated with pathognomonic storage products not only in the central nervous system (CNS) but also in extracerebral tissues such as sweat glands and lymphocytes. These tissues are easily accessible and thus function as "windows to the CNS". In addition, there are new methods that overcome limitations of conventional electron microscopy and may improve ultrastructural diagnostics. This is particularly important for the correct classification of viral particles such as SARS-CoV‑2, leading to abetter understanding of COVID19-associated diseases in the CNS and peripheral nervous system.

Causes of hereditary metabolic diseases in patients presenting with developmental delay

Objective: Developmental delay has many causes such as intrauterine infections, brain malformations, chromosomal anomalies, metabolic diseases. Between 0.8% and 15% of developmental delays are due to inherited metabolic diseases. Early diagnosis of these patients is very important in terms of the fact that some of them can be treated and also genetic counseling can be given to the family. In this study, it is aimed to emphasize the importance of reporting the clinical, biochemical and imaging characteristics, follow-up and treatment processes of the patients diagnosed with hereditary metabolic disease in patients with unexplained developmental delay/intellectual retardation, followed by the Metabolism 4 outpatient clinic of Başakşehir Çam and Sakura City Hospital. Materials and Methods: This retrospective study was conducted on the data obtained from the medical files of 192 patients aged 0-18 years, who were followed up with developmental delay/intellectual retardation between May 2021 and May 2022 in the metabolism 4 outpatient clinic of our tertiary care center. Results: The female/male ratio of the patients was 13/36, and the age range was between 3 months and 17 years. 34 patients were diagnosed with a hereditary metabolic disease and 15 patients with a non-metabolic genetic disease. There was consanguineous marriage in 23/32 of the patients with hereditary metabolic disease and 6/15 of the other patients. The most common Inherited metabolic disease groups are mitochondrial diseases, and lysosomal storage diseases. Discussion: Patients can present at any age, and hereditary metabolic disease group has an important place in the etiology and has a great importance in terms of including many treatable diseases. For this reason, referral of patients who apply to outpatient clinics with developmental delay/intellectual retardation to metabolism outpatient clinics is of vital importance in terms of diagnosis, treatment, family screening and genetic counseling.

Novel Mutation of Hydroxymethylbilane Synthase in a Case of Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome.

Acute intermittent porphyria (AIP) is an autosomal, dominant, hereditary metabolic disease caused by an inherited deficiency of hydroxymethylbilane synthase (HMBS), a crucial enzyme in the heme biosynthetic pathway. It can affect the central, peripheral, and autonomic nervous systems. We report a 23-year Chinese woman who presented with severe abdominal pain, convulsions, constipation, tachycardia, quadriparesis, and hyponatremia, accompanied by posterior reversible encephalopathy syndrome (PRES). The clinical diagnosis of AIP was made after positive urine Watson-Schwartz test for porphobilinogen (PBG). Genetic testing is important for AIP patients in confirming the diagnosis. We identified a new insertion mutation in intron 14 [c.1005dupC (p.I336Hfs*23)] of the HMBS in her genomic DNA. Timely and accurate treatment of AIP may improve disease prognosis. Key Words: Acute intermittent porphyria, Mutation, Posterior reversible encephalopathy syndrome.

Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management.

Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.

Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States.

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent LT. The 1- and 5-year post-LT survival rates in patients with HH were 88.7% (95% confidence interval [CI], 85.4%-91.4%) and 77.5% (95% CI, 72.8%-81.4%), respectively, and were comparable with those in the propensity-matched CLD cohort ( p value = 0.96). Post-LT survival for HH was lower than for Wilson's disease, another hereditary metabolic liver disease with similar LT volume ( n = 365). Predictors for long-term (5-year) post-LT mortality included presence of portal vein thrombosis (hazard ratio [HR], 1.96; 95% CI, 1.07-3.58), obesity measurements greater than Class II (HR, 1.98; 95% CI, 1.16-3.39), and Karnofsky performance status (HR, 0.98; 95% CI, 0.97-0.99) at the time of LT. The leading cause of post-LT death ( n = 145) was malignancy (25.5%), whereas cardiac disease was the cause in less than 10% of recipients. In conclusion, short- and long-term survival rates for HH are excellent and comparable with those of other LT recipients. Improving extrahepatic metabolic factors and functional status in patients with HH prior to LT may improve outcomes.

Glutaric acidemia type 1 (clinical cases)

Glutaric aciduria type 1 (glutaryl-CoA dehydrogenase deficiency, glutaric acidemia type 1) (OMIM 231670) is an autosomal recessive disease caused by mutations in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). Glutaryl-CoA dehydrogenase (GCDH) plays an important role in the degradation metabolism of L-lysine, L-hydroxylysine and L-tryptophan. The insufficiency or absence of the enzyme leads to the accumulation of by-products of degradation of such amino acids as glutaric acid, 3-hydroxyglutaric acid, glutarylcarnitine (C5DC-acylcarnitine) and glutaconic acid. The accumulation of glutaric acid and 3-OH-glutaric acid causes neurotoxicity. Glutaric aciduria type 1 can manifest itself in early childhood with encephalitis-like crises: from three months to three years as GA-1 with infantile onset or from the age of six years as the late onset of GA-1. It is characterized by progressive neurological motor disorders, with the appearance of various types of hyperkinesis in combination with spasticity, a high incidence of disability and mortality. In about 25% of cases, the disease has a subacute course and manifests over the first year of life with a delay in psychomotor development, the gradual development of hyperkinetic syndrome, and spasticity. Awareness of doctors and alertness regarding diseases from the group of hereditary metabolic diseases will help to carry out therapy in a timely manner both in the acute period and in the appointment of long-term therapy to prevent disability of patients.

Quantitative Detection of Amino Acids and Carnitine in Human Blood and Quality Control of Peptide Drugs

In order to deal with the biochemical metabolic disorder and the lack of end metabolites caused by hereditary metabolic diseases, a quantitative detection method of amino acids and carnitine in human blood and the quality control method of polypeptide drugs were proposed. First, a method for the detection of 10 amino acids and 32 acylcarnitine metabolites in human blood was established and analyzed by liquid chromatography tandem mass spectrometry. Through the experimental research on typical peptide drugs, combined with the classical synthesis process and the PLS-DA model of human body in different regions, the relevant detection methods for the quality control of peptide drugs were established, which provided a reference for the formulation of peptide drug quality standards. The experimental results show that the quantitative detection method proposed in this paper can effectively detect the content of most amino acids and acylcarnitine. The classical detection method achieved a loss of 16.74% smaller mass-to-charge ratio, and based on this, the quantitative standard for polypeptide drug delivery was determined, which verifies the correctness and superiority of the detection method in this paper.

Misdiagnosis in mucopolysaccharidoses.

Mucopolysaccharidosis (MPS) is a group of 13 hereditary metabolic diseases identified in humans (or 14 diseases if considering one MPS type described to date only in mice) in which an enzymatic defect results in the accumulation of glycosaminoglycans (GAG) in the lysosomes of cells. First of all, as a result of GAG storage, the proper functioning of the lysosome is disturbed; then, the cells, and finally, tissue, organs, and the whole organism malfunctions are observed. Due to the rarity, heterogeneity, and multi-systemic and progressive nature of MPS, they present a major diagnostic challenge. Due to the wide variation in symptoms and their similarity to other diseases, MPS is often misdiagnosed, usually as neurological diseases (like autism spectrum disorders, psychomotor hyperactivity, and intellectual disability) or rheumatology and orthopedic disorders (like juvenile idiopathic arthritis, Perthes disease, rickets, and muscular dystrophy). In this review article, we present the problems associated with the possibility of misdiagnosing MPS, discuss what diseases they can be confused with, and suggest ways to reduce these problems in the future.

The Porphyrias.

The porphyrias are clinically variable and genetically heterogeneous, predominantly hereditary metabolic diseases, which are caused by a dysfunction of specific enzymes in heme biosynthesis. Here, we provide an overview of the etiopathogenesis, clinic, differential diagnosis, laboratory diagnostics and therapy of these complex metabolic disorders and cover in detail the most common form of porphyria worldwide (porphyria cutanea tarda), the most frequent childhood porphyria (erythropoietic protoporphyria), and the most common neurocutaneous porphyria (variegate porphyria).

ПЕРВЫЙ СЛУЧАЙ ВЫЯВЛЕНИЯ МУКОПОЛИСАХАРИДОЗА VI ТИПА В РЕСПУБЛИКЕ СЕВЕРНАЯ ОСЕТИЯ – АЛАНИЯ: КЛИНИЧЕСКИЕ ХАРАКТЕРИСТИКИ И РЕЗУЛЬТАТЫ ЛЕЧЕНИЯ

Mucopolysaccharidoses (MPS) are a group of rare hereditary metabolic diseases caused by the accumulation of glycosaminoglycans in organs and tissues. Due to severe disabling course and the presence of specific enzyme replacement therapy for some types, they are included in the list of orphan diseases. The quality of life of patients with MPS improves significantly on condition of early diagnosis, timely prescription of pathogenetic therapy and treatment of comorbidities. From 2000 to 2020 in the Republic of North Ossetia – Alania, 165,149 children were born. During the study period, one case of MPS type VI was registered. Thus, the frequency of this pathology was 1:165,149 newborns. Enzyme replacement therapy for the observed patient is carried out for 6 years. Considering the positive dynamics of growth, a decrease in joint stiffness, no changes in the hemogram, a decrease in the size of the liver in dynamics, a stable picture according to the MRI of the brain in the observed patient, therapy with Naglazim should be recognized as effective.

Опыт неонатального скрининга на 37 наследственных болезней обмена веществ методом тандемной масс-спектрометрии в Приморском крае

Введение. Частота наследственных болезней обмена веществ (НБО) по зарубежным литературным данным составляет около 1:5000 живых новорожденных. В ряде стран мира и в большинстве регионов РФ скрининг новорожденных проводится только на 5 заболеваний, хотя спектр наследственных заболеваний, для которых разработаны методы лечения, гораздо шире. Новый этап в неонатальном скрининге начался с появлением тандемной масс-спектрометрии (ТМС), технологии, существенно улучшающей скрининг и расширяющей список выявляемых нарушений, поддающихся лечению и ранее не диагностируемых скрининг-программами. Цель: оценить результаты неонатального скрининга методом ТМС на 37 НБО и частоту НБО в Приморском крае. Методы. За период 2017-2021 гг. с использованием ТМС проведен расширенный скрининг новорожденных в Приморском крае на 37 НБО. Обследовано 68481 новорожденных. Все выявленные случаи подтверждены молекулярно-генетическими методами в ФГБНУ «МГНЦ». Результаты. В результате обследования более 68 тыс. новорожденных выявлены 8 детей с фенилкетонурией, 4 пациента с недостаточностью очень длинноцепочечной ацл-КоА дегидрогеназы жирных кислот, 2 пациента с гомоцистинурией, 2 пациента с глутаровой ацидурией, 1 пациент с лейцинозом, 1 пациент с недостаточностью трифункционального митохондриального белка. Еще 12 детей в настоящее время находятся под динамическим наблюдением и среди них высока вероятность выявления НБО. Частота подтвержденных НБО составила 1:3805 новорожденных. Предполагается, что фактическая частота выше по целому ряду технических, организационных и социальных причин. Выводы. Полученные результаты убедительно демонстрируют, что неонатальный скрининг методом ТМС является эффективным элементом клинической практики, позволяющим снижать заболеваемость, инвалидность и смертность населения от наследственных болезней обмена. Background. The birth incidence of inherited metabolic disorders (IMDs) according to foreign literature data is about 1:5000. In some countries of the world and in most regions of the Russian Federation, newborns are screened for only 5 diseases, although the spectrum of hereditary diseases for which treatments have been developed is much wider. A new stage in neonatal screening was initiated with the advent of tandem mass spectrometry (TMS), a technology that significantly improves screening and expands the list of detectable disorders that are treatable and previously undiagnosable by screening programs. Aim: to evaluate the results of newborn screening by TMS for 37 IMD and to estimate the incidence of IMDs in Primorsky Krai. Methods. Extended neonatal screening in Primorsky Krai for 37 IMDs was performed using TMS in the period 2017-2021. 68481 newborns were examined. All detected cases were confirmed by molecular genetic methods in Research Centre for Medical Genetics (RCMG). Results. As a result of the examination of more than 68,000 newborns, various IMDs were identified in 8 children with phenylketonuria, 4 patients with very long-chain acyl-CoA fatty acid dehydrogenase deficiency, 2 patients with homocystinuria, 2 patients with glutaric aciduria, 1 patient with leucinosis, 1 patient with deficiency of trifunctional mitochondrial protein. Additionally, 12 children are currently under dynamic observation, and among them, there is a high probability of detecting IMD. All disorders from the group of other diseases were confirmed by specialists of RCMG. The incidence of confirmed IMD was 1:3805 newborns. The actual incidence was assumed to be higher for a variety of technical, organizational, and social reasons. Conclusions. The results convincingly demonstrate that newborn screening by the TMS method is an effective and extremely necessary element of clinical practice to reduce morbidity, disability and mortality from IMDs.

Experience of using a probiotic strain of Enterococcus in long-term nutritional support for premature children

Objective. To evaluate the experience of using a probiotic strain of enterococcus in long-term nutritional support of premature infants.Characteristics of children and research methods. The children were selected in 2014–2015. The study included 11 premature babies of the first year of life, treated with antibiotics for a long time. Inclusion criteria: prematurity of any severity, signed informed consent from parents to conduct an outpatient rehabilitation program for children, including long-term nutritional support with a probiotic strain of enterococcus. Exclusion criteria: gross congenital malformations; hereditary metabolic diseases, severe forms of organic pathology of the central nervous system. Exclusion criteria: severe forms of somatic and infectious pathology, use of other probiotics. The probiotic strain of enterococcus – E. faecium L3 (No. RU. 77.99.26.009.Е.002272.02.11) in the liquid form (biomass grown on a dairy-free basis) with a titer of at least 108 CFU/ml was orally administered to children 1 ml 2 times a day while eating. The authors evaluated safety and clinical efficacy of long-term use of the probiotic strain of enterococcus.Results. The authors noted the effectiveness of long-term use of a probiotic strain of enterococcus as nutritional support for premature infants for adequate psychomotor and physical development. They revealed the disappearance of the manifestations of atopic dermatitis while taking a probiotic strain of enterococcus. In the course of the study, the safety of long-term intake of a probiotic strain of enterococcus was established as an integral part of the rehabilitation program for premature babies, who completed their nursing in a hospital.Conclusion. The continuation of studies to assess the clinical efficacy of long-term intake of probiotics in children of the first year of life who were born prematurely and received antibiotics for a long time can be considered very promising.

Гипохолестеринемия – важный симптом редких болезней

Hypocholesterolemia is an important symptom that may indicate the presence of severe hereditary metabolic disease or acquired secondary pathology. This lecture discusses the criteria for hypocholesterolemia in children, issues of cholesterol metabolism and its disorders, and the most common causes of hypocholesteremia. Issues of pathogenesis, clinical picture, diagnosis, and treatment of cholesterol synthesis disorders (Smith–Lemli–Opitz syndrome) and abetalipoproteinemia are considered in detail, and clinical cases of patients with these diseases are presented. Key words: hereditary metabolic diseases, hypocholesterolemia, Smith–Lemli–Opitz syndrome, abetalipoproteinemia

Značaj novorođenačkog skrininga u prevenciji retkih metaboličko-endokrinoloških poremećaja

Indicating the importance of early diagnosis and treatment of diseases at the earliest age of life, newborn screening is included in the mandatory form of health care for children and is carried out in countries around the world. Newborn screening includes severe hereditary metabolic and endocrinological diseases, which do not immediately manifest themselves clinically, while in the later course they lead to impaired growth and development with a high percentage of physical and psychological disability. An early diagnosed disease enables a quick therapeutic approach so that the disease does not progress, and adequate growth and development of the child. The goal of newborn screening is the early detection of newborn diseases where early diagnosis and treatment will lead to a significant reduction in mortality, morbidity and disability. The aim of this work is to present some of the most common metabolic and endocrinological diseases that are included in the newborn screening program in Montenegro and the surrounding countries, as well as to familiarize with the complications of undiagnosed diseases in a timely manner, therapeutic possibilities and the prognosis of the disease after timely treatment.

Синдром Жубер у ребенка с синдромом Жильбера

Joubert syndrome is a heterogeneous disease from a group of ciliopathies that share a specific malformation of the midbrain and hindbrain, known as the «molar tooth sign» according to MRI of the brain. This article presents a clinical case of a rare hereditary disease – Joubert syndrome caused by mutations of C.610A>G in the OFD1 gene. The history of the disease was traced to the age of 6 years 9 months. Clinical manifestations of the disease in the patient since birth were jaundice, respiratory disorders, diffuse hypotonia, convergent strabismus, delayed physical and psychomotor development. After excluding the main groups of hereditary metabolic diseases, the patient underwent a brain MRI, where a specific anomaly of the cerebellar and brainstem structure, known as the «molar tooth sign», was revealed. Subsequently, the diagnosis was clarified by the molecular genetic method (Sanger sequencing). Key words: children, Joubert syndrome, ciliopathy, OFD1 gene

Nerve excitability study – a method to assess the pathophysiology of peripheral nervous system disorders

Nerve excitability study is an interesting extension of classical neurography. The principle of the test is to stimulate the nerve with a long-term depolarising or hyperpolarising stimulus, followed by a test stimulus that induces a complex motor or sensory potential of a given amplitude. The analysis of the intensity of the test stimulus used in chronic depolarisation or hyperpolarisation of the nerve fibre allows for the assessment of changes in nerve excitability. The median nerve is stimulated, and it is possible to assess the excitability of sensory or motor fibres. Nerve excitability study is the only method to evaluate the function of neuronal membrane ion channels in vivo. Test results are impacted by the following membrane-related factors: voltage-gated sodium and potassium ion channels, sodium and potassium ATPase, as well as the degree of fibre myelination and the levels of extracellular and intracellular electrolytes. Nerve excitability study yields a result in the form of a series of complex peripheral nerve excitability parameters, such as the relationship between the stimulus and the excitation threshold, rheobase, fibre chronaxie, threshold electrotonus, and reactivation after action potential. Nerve excitability study helps assess the pathophysiology of nerve fibre damage in various disorders of the peripheral nervous system, such as hereditary polyneuropathies, neurodegenerative or metabolic diseases. The test is highly sensitive, e.g. it shows pre-symptomatic excitability changes. It can also be used to monitor treatment outcomes in metabolic and drug-induced polyneuropathies and to search for peripheral markers of central nervous system channelopathies.

Characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody

Objective: To analyze the characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody type 1 (anti-LC1), in order to provide references for clinical and differential diagnosis. Methods: The clinical data of 23 832 inpatients and outpatients with positive anti-LC1 autoantibodies detected in routine autoantibody test from January 2010 to January 2020 were retrospectively analyzed, and their clinical and laboratory indexes were compared. Western blotting was used to detect anti-LC1, anti-soluble liver antigen antibody (anti-SLA), anti-glycoprotein 210 antibodies and anti-nucleosome 100 antibodies. Indirect immunofluorescence assay was used to detect anti-nuclear antibody (ANA), anti-mitochondrial antibody, anti-Smooth muscle antibody (ASMA), anti-liver and kidney microsomal antibody (anti-LKM) and other autoantibodies. Normally distributed measurement data between the two groups were compared by independent-sample t-test, and the multiple groups comparison were compared by one-way analysis of variance. Non-normally distributed measurement data were compared by non-parametric rank sum test. Results: 38 anti-LC1 positive patients were detected in 23832 autoantibody tests. The age of initial diagnosis ranged from 11.0 to 84.0 (50.6 ± 16.0) years. There were 8 males (21.1%) and 30 females (78.9%). A total of 31 cases (81.6%) were positive for anti-LC1 and ANA, and the dominant karyotype was speckled pattern, accounting for 54.8%. Five cases (13.2%) were positive for ASMA, and no simultaneous positive with anti-LKM or anti-SLA. Among the 38 anti-LC1 positive patients, 9 were diagnosed with autoimmune hepatitis (AIH), 6 with possible AIH, 6 with primary biliary cholangitis (PBC), 8 with hepatitis B, 2 with hepatitis C, 1 with alcoholic liver disease, 2 with non-alcoholic fatty liver disease, 1 with drug-induced liver injury, 1 with hepatolenticular degeneration, and 2 with tumor. Confirmed and probable AIH cases accounted for 39.5% (15/38) of anti-LC1 positive cases. Among anti-LC1 positive patients, 47.4% (18/38) had entered the stage of liver cirrhosis. AIH group globulin level was higher than HBV group (P = 0.006) and other disease groups (P = 0.001). AIH group IgG level was higher than PBC group (P = 0.027), HBV group (P = 0.009) and other disease groups (P = 0.004). the of the PBC group IgM level was higher than AIH group (P = 0.003), HBV group (P = 0.003) and other disease groups (P = 0.006). Conclusion: Anti-LC1 is not only detected in AIH, but also observed in patients with primary biliary cholangitis, hepatitis B and C, alcoholic and non-alcoholic liver disease, drug-induced liver injury, hereditary metabolic liver disease and tumor. In addition, it is mainly female gender dominance and nearly half of ANA-positive young, middle-aged and elderly patients develop liver cirrhosis. For the diagnosis of type 2 autoimmune hepatitis, whether anti-LC1 is a specific antibody needs further research, but if AIH is highly suspected, this antibody can be used as a substitute.

Updating preventive measures of children disability

The article provides an overview of special literature, which gives an opportunity to redefine some issues of disability prevention in children with rare (orphan) diseases, which will improve the organizational measures in this area. The prevention of children’s disability is considered as a system of measures to protect the health of the mother and child throughout childhood. The early disability prevention system in children and support for families raising children with disabilities remain among the main priorities of the State social policy of the Russian Federation. The authors describe modern technologies for reducing the genetic burden in the population from the point of view of preventing hereditary and congenital pathologies. They identify the priority areas of disability prevention in children with rare (orphan) diseases, i.e. introduction of prenatal and preimplantation diagnostics; use of the Prenatal Consultation organizational model; conducting a wider screening for congenital and hereditary metabolic diseases with the inclusion of the most common nosological forms of rare (orphan) diseases; finding pathogenetic therapy methods; increasing the knowledge of pediatricians about rare (orphan) diseases.

A review of some common African spices with antihypertensive potential.

Hypertension is the most common non-communicable disease, with about 1.28 billion hypertensive people worldwide. It is more prevalent in men than women and more common in the elderly. Hereditary, age, obesity, lifestyle, diet, alcohol, and chronic metabolic diseases are the major risk factors of hypertension. Treating hypertension is a complex process as there are several mechanisms responsible for its pathogenesis; hence, a combination of several drugs is used for managing hypertension. Drugs used in managing hypertension are expensive and often come with associated side effects; thus, there is need for alternative means of managing this life-threatening disease. These drugs do not achieve the recommended blood pressure target in most people; more so majority of people with hypertension do not follow the treatment regimen religiously. Some Africans have been reported to become normotensive as a result of dietary consumption of spices. Several spices have been used over the years in Africa to manage hypertension. The aim of this review is to evaluate the ethnomedicinal use, bioactive phytochemical composition, bioactive compounds present, and pharmacological applications of spices commonly used in Africa for managing hypertension. Most of the plants used contained polyphenols, flavonoids, tannins, anthraquinone, flavonoids, cardiac glycosides, and saponins. Dietary supplementation of Xylopia aethiopica and other spices in diet have been proven to significantly reduced plasma angiotensin-I-converting enzyme (ACE) than simvastatin (the reference drug). Toxicological, histological, and hematological evaluation revealed that acute and chronic consumption of most of these spices are safe. Studies have also revealed that some of the spices can be used as alternative therapy alongside usual antihypertensive medications. PRACTICAL IMPLICATION: The prevalent rate of hypertension is on the increase in both the developed and developing countries. People often skip medication due to their busy schedule and anti-hypertensive potential side effects; however, this is not the case with food/spices as most people consumed them daily. Deliberate, right combinations and consistent incorporation of spices with proven anti-hypertensive potential into our diet may be of great benefit in normalizing blood pressure and mitigate other complications on the heart and vital organs.

Inherited metabolic diseases: aminoacidopathies, organic acidemia, defects of mitochondrial β-oxidation. A brief overview

Inherited metabolic diseases are a large group of inherited monogenic diseases. Metabolic disorders can cause child disability and mortality. Tandem mass spectrometry is a powerful technology that allows to diagnosis a large number of hereditary metabolic diseases. Clinical manifestations are variable, but more often the damages of nervous system, heart, liver, kidneys, hyperammonemia, hypo/hyperglycemia take place. The disease can make its debut at any age, but the severe forms of the disease manifest at infancy. Early diagnosis and treatment can significantly improve the prognosis; many countries expand the list of diseases included in screening programs. At the beginning of 2021 in most regions of the Russian Federation mass newborn screening is carried out for five hereditary metabolic diseases. The age and the range of clinical manifestation are variable; therefore, knowledge of this pathology is very important both for pediatricians and therapists, and for specialized doctors. The article presents a brief description of next groups of metabolic diseases: aminoacidopathies, organic acidurias and fatty acid oxidation defects.