Juvenile Form Research Articles

GRANULOSA TUMORS: ABOUT 10 CASES

Granulosa tumors arise from the mesenchyme and sex cords of the ovary. They are quite rare. Theyrepresent 0.6 to 3% of all ovarian tumors and 5% of ovarian malignancies. They are the mostfrequent tumors of the sexual cords and stroma. The purpose of our study:To describe the epidemiological, anatomical-clinical and evolutionary characteristics of granulosatumors and to study the different prognostic factors. Materials and methods:Our retrospective study covers 10 cases of ovarian granulosa tumor diagnosed at the gynecologyobstetrics department of the CHU Mohammed VI of Oujda. Over a period of 5 years, from September2016 to September 2021. Results:- The average age of onset of the adult form is 58.4 years (35-38-52-57-66-81). And that of theoccurrence of the juvenile form, is 18.6 years (18-19-22-31).Clinical signs were mainly dominated by abdominal distension, chronic abdominal-pelvic pain andmetrorrhagia.All patients had clinically palpable pelvic tumors.Suprapubic pelvic ultrasound was performed in all our patients.It allowed to link the pelvic mass to its adnexal origin, with an average size, 141.5mm, variablebetween 63mm and 220mm. The CT scan was performed in all our patients. It allowed us to determine the size of the masses andtheir relationship with the surrounding structures.The histological study concluded in a granulosa tumor adult type in 60% of the cases and in agranulosa tumor juvenile type in 40% of the cases.80% of patients received conservative treatment, 20% received radical treatment.60% of our patients have received chemotherapy.No patient had radiotherapy. One patient had a recurrence and all patients are still alive after surgical treatment. Conclusion: Granulosa tumors are rare, of the group of tumors of the sexual cords and the ovarian stroma. The adult forms are of slow evolution, often diagnosed at an early stage are potentially malignant tumors, the recurrences often very late (10-20 years) their treatment is based essentially on surgery more or less chemotherapy. Juvenile forms, rare (5%) with good prognosis. Prolonged post-therapy follow-up is necessary because of late recurrences for Adult forms, frequent and early for juvenile forms.

Progress in Biological Therapies for Adult-Onset Still’s Disease

Adult-onset Still’s disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effective in the treatment of systemic and articular inflammation of AOSD patients; however, novel compounds with different properties and targets are now available and others are being studied. In this review, starting from the pathogenesis of AOSD, we summarized the current and emerging biological therapies, possible effective agents for achieving AOSD control and remission.

Latent effect of larval rearing environment on post-metamorphic brain growth in an anuran amphibian

Early development is highly susceptible to environmental influence. We evaluated the role of larval visual environment on brain morphology plasticity in late larval and juvenile stages of Bombina orientalis, an anuran amphibian changing from an aquatic to a terrestrial habitat after metamorphosis. Manipulation of the visual environment was achieved by rearing larvae in normal and darkened water. The juveniles were exposed to normal lighting conditions after metamorphosis, allowing to assess if plastic effects persisted or emerged after metamorphosis. The darkness treatment accelerated development before slowing it down substantially, allowing controls to metamorphose earlier. Although larvae reared in darkened water had the same relative brain size as controls by the end of the larval period, juveniles that had been reared in darkened water as larvae had brains that were 14.4% smaller than juveniles that had been reared under control conditions. Conversely, relative telencephalon size was 6.7% larger in juveniles previously reared in darkened water compared with controls, again with no effect of darkened water seen by the end of the larval period. Unlike the latent effects seen on whole brain and telencephalon size, relative size of the optic tectum was significantly smaller in both larvae and juveniles exposed to the darkened water treatment. Therefore, the effects of visual restriction on juvenile brain form were a combination of latent (whole brain and telencephalon) and carry-over (optic tectum) developmental effects.

Systematic revision of Gyriabrus (Rodentia, Caviomorpha), a large dinomyid from the Neogene of South America

ABSTRACT Dinomyidae is a family of rodents including one extant species, Dinomys branickii, but with a high past diversity. Gyriabrus is a large dinomyid with euhypsodont cheek teeth and an occlusal pattern that changes throughout the ontogeny of the animal. Eight species of Gyriabrus have been described in the late Miocene to Pliocene of Argentina, Uruguay, Colombia and Brazil. The taxonomic status of Gyriabrus has been questioned, being considered as juvenile forms of other euhypsodont dinomyids. According to this study, Gyriabrus has a unique dental anatomy among euhypsodont dinomyids and is a valid genus. A study of the cheek teeth permitted to propose an ontogenetic series. All the species described from the late Miocene of Argentina (Ituzaingó Formation) and Uruguay (Camacho Formation) belong to Gyriabrus holmbergi (including G. glutinatus, G. rebagliattii, G. indivisus and G. teisseirei), representing different wear stages. ?Gyriabrus quadratus, G. latidens (late Pliocene? of Argentina) and ?G. royoi (late Miocene-Pliocene of Colombia), all based on isolated teeth, are considered as valid species, pending future findings that allow a deeper comparison. This study contributes to the knowledge of the systematics, taxonomy and anatomy of extinct Dinomyidae, which are essential for future studies of the evolutionary history of the group.

EP005: Complex glycerol kinase deficiency and X-linked intellectual disability

Glycerol kinase deficiency (GKD) is caused by pathogenic variants of the GK gene on chromosome Xp21. Three forms of GKD are recognized, characterized as infantile, juvenile, and adult forms. While the juvenile and adult forms are recognized as isolated GKD, the infantile form manifests itself as part of the Xp21.3 contiguous gene deletion syndrome, also known as complex GKD. This syndrome is composed of genes associated with Duchenne muscular dystrophy (DMD), X-linked congenital adrenal hypoplasia (NR0B1), and intellectual disability (IL1RAPL1).

Arthroscopic Ulnohumeral Joint Debridement and Transolecranon Microfracture for Osteochondritis Dissecans of the Humeral Trochlea

Osteochondritis dissecans of the humeral trochlea is a rare cause of elbow pain adolescents. Despite being a juvenile form of osteochondritis dissecans, spontaneous resolution is not uniform, and more than one-half of patients experience ongoing pain, crepitus and loss of motion. Traditionally, nonsurgical management has been favoured as distal trochlea articular lesions were only accessible via olecranon osteotomy. Consequently, the threshold for intervention is high as the recovery prolonged. We present our technique of accessing the trochlear osteochondritis dissecans via ulnohumeral joint arthroscopy with transolecranon microfracture, which enables these lesions to be managed with reduced morbidity.

Вплив основних положень Міжнародного керівництва з інтенсивної терапії тяжкого сепсису та септичного шоку — 2012 із додатковою ентеропротекцією на перебіг септичного процесу і вираженість енцефалопатії в структурі поліорганної недостатності

У статті проведено аналіз результатів впливу ключових положень Міжнародного керівництва з інтенсивної терапії тяжкого сепсису та септичного шоку — 2012, доповнених ентеропротекцією, на перебіг септичного процесу і вираженість енцефалопатії в структурі поліорганної недостатності. Заключення аналізу базувалося на підставі динаміки кількісних характеристик фізіологічного патерну CI-DO2-VO2; рН інтрамукозного, шкал GCS, APACHE II, SOFA; показників синдрому системної запальної відповіді; концентрації цитокінів (TNF-α, IL-1, IL-4, IFN-α); імуноглобулінів (IgA, IgM, IgG). Незважаючи на відновлення загальної оксигенації в умовах супранормальних значень DO2-VO2, на 3-тю — 5-ту добу відмічали чотири критерії SIRS, що розцінювалося як імовірність ризику уповільненої регресії синдрому запальної відповіді в подальшому. Сказане вище знайшло своє підтвердження в клінічному показнику лейкоцитів на 7-му добу — 15,18 • 109/л і незрілих форм — 11,88 %. Бали за шкалами APACHE II і SOFA, знизившись порівняно з такими на 5-ту добу, «застигли» на цьому рівні на 7-му добу. Неврологічна симптоматика на 7-му добу оцінювалася як сопор — 10,88 бала. Максимально високі концентрації прозапальних цитокінів на 5-ту — 7-му добу можна пояснити їх реперфузійним походженням після відновлення спланхнічного кровообігу. При цьому позитивним було перевищення IL-4 на 7-му добу свого рівня на 5-ту добу на 77,42 %. Використання сорбентів виявилося неефективним за наявності гострих ерозій і виразок шлунково-кишкового тракту для регенерації ентероцитів і запобігання шлунково-кишковим кровотечам навіть у поєднанні з інгібіторами протонної помпи. Початково передбачувана летальність за сумою балів шкали APACHE II становила 51 %, справжня летальність — 35,5 %, тобто застосування ентеросорбенту призвело до зниження летальності на 15,5 %.

Genetic and phenotypic variability in adult patients with Niemann Pick type C from Serbia: single-center experience.

Niemann Pick type C is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 and NPC2 genes. It is a neuro-visceral disease with a heterogeneous phenotype. Clinical features depend on the age at onset. Visceral manifestations are more prominent in the early onset (infantile) form, while neuro-psychiatric symptoms are more prominent in the late disease onset (juvenile and adult forms). A total number of 150 patients have been screened for changes in NPC1 and NPC2 gene at the Neurology Clinic, University Clinical Centre of Serbia in the period 2012-2020. Clinical data were extracted for patients with biallelic mutations. Fifteen patients carried biallelic mutations in the NPC1. Out of eight different reported NPC1 variants, four are novel (c.1204_1205TT>GC, p.F402A; c.2486T>G, p.L829R; c.2795+5 G>C; c.3722T>A, p.L1241*). The mean age at the disease onset was 20.3 ± 11.9years with the average diagnostic delay of 7.7 ± 4.3years. Movement disorders and psychiatric or cognitive disturbances were the most common initial symptoms (in 33% and 28% patients, respectively). The average age at the first neurological manifestation was 21 ± 12.0years. At the last examination, eye movement abnormalities (vertical slow saccades or vertical supranuclear gaze palsy), and ataxia were present in all patients, while dystonia was common (in 78.6% of patients). Presence of c.2861C>T, p.S954L mutation in homozygous state was associated with older age at the neurological symptom onset. Clinical findings were in line with the expected, but the diagnostic delay was common. We hypothesize that the presence of c.2861C>T, p.S954L mutation may contribute to the phenotype attenuation.

COMPOUND HETEROZYGOTE REASON FOR JUVENILE FORM OF TAY-SACHIS DISEASE -CASE REPORT

Tay-Sachs diseases are group of rare autosomal recessive lysosomal disorders, GM2-gangliozidoses. They are progressive neurodegenerative diseases, caused by a mutation in the enzyme β-hexosaminidase A. Depending on the time of presentation of symptoms, there are three forms: infantile, juvenile and adult. We present a 8 year old patient, who is presented at the age of 4 with progressive deterioration in psychomotor and speech skills, pyramidal symptoms, ataxia and muscle weakness. The EEG showed bihemispheric fast spike waves and the MRI showed no findings of organic disease. Finally a molecular genetic testing was made, which proved the diagnosis of juvenile form of Tay-Sachs disease. It was determined that the patient is a compound heterozygote, with two different mutations in the alleles of the HEXA gene, one  inherited from the mother and the other one from the father. The juvenile Tay-Sachs disease is characterized with beginnig between the age of 2 to 10 years old. Clinically it is presented with muscle weakness, incoordination, ataxia, dysarthria, dysphagia and progressive spasticity. It progresses to development of dementia, convulsions, blindness and vegetative state with decerebrate rigidity and death by the age of 15. It is inherited autosomal recessive with one mutation present on both alleles of the HEXA gene. Treatment options for Tay-Sachs disease currently are only symptomatic and supportive. There are ongoing researches for curative treatments for Tay-Sachs, like enzyme replacement, chaperone, substrate reduction and gene therapy. Keywords: Tay-Sachs disease, juvenile form, compound heterozygote.  

Tumor of the Granulosa of the Ovary About a Case

Ovarian granulosa tumors are very rare; they belong to the group of sex cord and stromal tumors. Their slow evolution in the adult forms which are more frequent (95%) and less aggressive than the much rarer juvenile forms. The exact etiology of these tumors is unknown, but higher than normal estrogen levels are frequently found in women with ovarian granulosa cell tumors. A woman's menstrual status with excess estrogen is related to the presence of certain symptoms such as: early puberty in young women, increase in the size of the abdomen, menstrual cycle disorders in pre menopause or bleeding abnormal uteri in postmenopausal women. The most frequent ultrasound aspect is the solid-cystic aspect and pathological examination remains the diagnostic key. The treatment is essentially surgical, but sometimes associated with complementary therapies such as: chemotherapy, radiotherapy, hormone therapy. Recurrences occur late, hence the importance of post-therapeutic follow-up. Some aggressive forms relapse and progress more rapidly, which justifies rigorous therapeutic monitoring. The prognostic factors for recurrence identified in the literature are the FIGO stage, the presence of residual tumor and the tumor size. We report a case of observation and we draw attention to the epidemiological, clinical particularities, as well as the various prognostic factors in order to carry out a better therapeutic management.

The Action of Recombinant Human Lysosomal α-Glucosidase (rhGAA) on Human Liver Glycogen: Pathway to Complete Degradation

Glycogen is present in all tissues, but it is primarily stored in the liver and in muscle. As a branched chain carbohydrate, it is broken down by phosphorylase and debrancher enzymes, which are cytoplasmic. It is also degraded by a lysosomal α-glucosidase (GAA) also known as acid α-glucosidase and lysosomal acid α-glucosidase. The deficiency of GAA in patients is known as Pompe disease, and the phenotypes as infantile, juvenile and later onset forms. Pompe disease is treated by enzyme replacement therapy (ERT) with a recombinant form of rhGAA. Following ERT in Pompe mice and human patients there is residual carbohydrate material present in the cytoplasm of cells. The goal of this work is to improve ERT and attempt to identify and treat the residual cytoplasmic carbohydrate. Initial experiments were to determine if rhGAA can completely degrade glycogen. The enzyme cannot completely degrade glycogen. There is a residual glycosylated protein as well as a soluble glycosylated protein, which is a terminal degradation product of glycogen and as such serves as a biomarker for lysosomal glycogen degradation. The glycosylated protein has a very unusual carbohydrate composition for a glycosylated protein: m-inositol, s-inositol and sorbitol as the major carbohydrates, as well as mannitol, mannose, glucose and galactose. This work describes the residual material which likely contains the same protein as the soluble glycosylated protein. The biomarker is present in serum of control and Pompe patients on ERT, but it is not present in the serum of Pompe mice not on ERT. Pompe mice not on ERT have another glycosylated protein in their serum which may be a biomarker for Pompe disease. This protein has multiple glycosylation sites, each with different carbohydrate components. These glycosylated proteins as well as the complexity of glycogen structure are discussed, as well as future directions to try to improve the outcome of ERT for Pompe patients by being able to monitor the efficacy of ERT in the short term and possibly to adjust the timing and dose of enzyme infusions.

YPK9 and WHI2 Negatively Interact during Oxidative Stress.

Yeast PARK9 (YPK9) shares homology with human ATP13A2, which encodes a polyamine transporter implicated in juvenile forms of Parkinson’s disease. We used YPK9 to gain insight into how ATP13A2 affects cell growth and sensitivity to oxidative stress. Surprisingly, the YPK9 deletion strain from the Saccharomyces cerevisiae deletion collection (YKO) in wildtype BY4741 (mating type a) grew faster and was more resistant to hydrogen peroxide than a commercial, putative parental BY4741 wildtype strain (BY4741COM). In contrast, deleting YPK9 from BY4741COM rendered it very sensitive to hydrogen peroxide, suggesting its background is different from that of the deletion collection. Whole-genome sequencing revealed that BY4741COM and BY4741COM ypk9∆ contain a novel premature stop codon near the 3′ end of WHI2 (WHI2G1324T), whereas the collection’s YPK9 deletion strain contains WHI2, which encodes a 486 amino acid protein, Whi2p. Replacing full-length WHI2 with the sequence coding for the predicted truncation (Whi2pE442*) rendered strains more sensitive to hydrogen peroxide, whereas the converse replacement rendered them more resistant. The sequences of WHI2 in 20 randomly chosen strains from the collection encode the full-length protein, indicating that the putative parental BY4741 WHI2G1324T strain’s genetic background differs from that of the deletion collection. Examination of WHI2 sequences in several commonly used wildtype S. cerevisiae strains and isolates revealed other Whi2p truncations that might yield altered phenotypes. Together, these results demonstrate a novel premature stop codon in WHI2 that renders yeast sensitive to hydrogen peroxide; they also reveal a negative genetic interaction between WHI2 and YPK9 in the presence of hydrogen peroxide in the BY4741 background.

Sucking of human blood by Placobdella costata (O. F. Müller, 1846) (Hirudinida: Glossiphoniidae): Case study with notes on body form.

Four events of Placobdella costata sucking human blood are described.Human blood was sucked by both adult and juvenile specimens of P. costata.The feeding strategies of juveniles under parental care are presented.New data on juvenile specimens' body form are presented.Information on the potential role of mammals in dispersion and habitat preferences of leeches P. costata is considered.

Paracoccidioidomycosis in an Elderly Simulating Cholangiocarcinoma

Paracoccidioidomycosis, the most prevalent deep mycosis in Latin America, is caused by dimorphic species of the genus Paracoccidioides, affects predominantly male rural workers between 30-50 years of age and is an important cause of morbidity and mortality. It can present in two clinical forms: acute/subacute or chronic. In rare cases paracoccidioidomycosis may simulate neoplasia and must be considered as a differential diagnosis of intra-abdominal tumors in endemic areas. We report an exuberant case of subacute paracoccidioidomycosis in an elderly lady, although it is more frequent in the juvenile form. Multiple facial skin lesions were associated with a wasting syndrome and extensive adenopathy including in the hepatic area, causing bile duct dilatation simulating a cholangiocarcinoma. Skin histopathology was diagnostic and antifungal treatment allowed complete resolution of cutaneous and systemic lesions, thus highlighting the merit of the dermatologist, who was fundamental for the conclusive diagnosis and institution of specific therapy, resulting in a favorable outcome.

Anatomy and histology of the thymus of American mink genotypes Standard, Sapphire, Lavander in the early postnatal period of ontogenesis

Data are presented on the thymus structure of American Mink of the Standard, Sapphire, Lavender colouring genotypes in the early postnatal period from birth to 180 days. The thymus is known to be a fully formed organ at birth. The anatomical structure of the thymus and its topography are not determined by genotype. At 45 days of age, the changes are manifested by an increase in the thymic lobule area and the brain matter therein, a decrease in the cortex area; the most intense growth of the thymus due to the rise in the number of lobules is noted. The thymus of mink at 45 to 90 days of age is characterised by an equalisation between the genotypes, increasing cortical area values to about the level of newborn mink with a corresponding increase in the cortical-brain index. The thymus of minks at the age of 90 to 180 days retains the typical morphological structure. Still, the signs of age involutive processes are seen – reduction of the lobule area, enlargement of the medulla, changes in the form of the organ (lobule fusion), increased signs of fat transformation thymus. Hassall’s corpuscles were found in the medulla in all periods of investigation. The number of Hassall’s bodies and their morphology depends on the functional activity of the thymus. In newborns, unicellular, young and juvenile forms predominate. In 45-day-old minks, young and immature forms predominate. In 90-day-old female and male Standard burros, young and quite often unicellular bodies are visualised, while mature and juvenile records are less common. In mink of the coloured genotypes, immature and youthful Hassall’s corpuscles are predominant. By 180 days, the number of mature and young corpuscles with signs of central cell destruction with detritus accumulation and cavity formation increases.

Differential diagnosis of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a disease with an X-linked recessive type of inheritance, belonging to a group of disorders with primary muscle damage, caused by pathogenic variants in the DMD gene and associated with dysfunction of the dystrophin protein. Since DMD is manifested by the gradual development of progressive, mainly proximal muscle weakness, the differential diagnosis is primarily carried out in the group of diseases with muscle damage - myopathies. Among these diseases, the leading candidates for differential diagnosis are hereditary myopathies (limb-girdle muscular dystrophies, facioscapulohumeral dystrophy, congenital muscular dystrophies, glycogenoses - the most common juvenile form of glycogenosis type II (Pompe disease)) and, much less often, congenital myopathies and other conditions of neuromuscular diseases). When conducting a differential diagnosis in a child with suspected DMD, the age of the onset of the disease, early initial clinical manifestations and the development of symptoms as they grow, genealogical analysis, laboratory tests (the level of creatine kinase, aspartate aminotransferase, alanine aminotransferase in blood serum), instrumental (electromyography, magnetic resonance imaging of the brain and muscles) and molecular genetics (polymerase chain reaction, multiplex ligation-dependent probe amplification, next-generation sequencing, Sanger sequencing, etc.) of studies, and in some cases, muscle biopsy data. Knowledge of the nuances of the differential diagnosis allows establishing a genetic diagnosis of DMD as early as possible, which is extremely important for the formation of the prognosis of the disease and the implementation of all available treatment methods, including pathogenetic therapy, and is also necessary for medical and genetic counselling of families with DMD patients.

IMAGING: EP.333 Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis

Recessive mutations in the TK2 gene lead to a mitochondrial disorder that manifests mainly as a progressive myopathy, which involves facial, cervical, axial, bulbar and respiratory muscles. The early and juvenile forms are the most frequent, but the late onset is probably least recognized and underdiagnosed. Our objective is to evaluate the diagnostic value of muscle MRI to facilitate the recognition of adult patients with myopathy related to TK2 deficiency (TK2d). 45 adult patients with a mitochondrial myopathy from 9 different Spanish centers were included.

Fibroepithelial tumours of the breast-a review.

Fibroepithelial tumours of the breast are biphasic neoplasms composed of both epithelial and stromal elements, including the common fibroadenoma and the infrequent phyllodes tumour. The admixture of epithelium and stroma in the fibroadenoma shows intra- and pericanalicular patterns, and may display a variety of histological changes. Fibroadenoma variants include the cellular, juvenile, myxoid and complex forms. The cellular fibroadenoma may be difficult to distinguish from the benign phyllodes tumour. Stromal mitotic activity can be increased in fibroadenomas in the young and pregnant patients. Phyllodes tumours, neoplasms with the potential for recurrence, show an exaggerated intracanalicular growth pattern with broad stromal fronded architecture and stromal hypercellularity. They are graded into benign, borderline and malignant forms based on histological assessment of stromal features of hypercellularity, atypia, mitotic activity, overgrowth and the nature of the tumour borders. Classification of phyllodes tumours is imperfect, compounded by tumour heterogeneity with overlapping microscopic features among the different grades, especially in the borderline category. Malignant phyllodes tumours can metastasise and cause death. Determining which phyllodes tumours may behave aggressively has been difficult. The discovery of MED12 mutations in the pathogenesis of fibroepithelial tumours, together with other gene abnormalities in the progression pathway, has allowed refinements in diagnosis and prognosis.

Editors' Note: Association of Age at Onset and First Symptoms With Disease Progression in Patients With Metachromatic Leukodystrophy

Metachromatic leukodystrophy is a neurodegenerative condition with a variable rate of progression that warrants more systematic investigation. In their natural history study of 98 patients with metachromatic leukodystrophy, Dr. Kehrer et al. summarize the prominent symptoms and age of symptom onset according to various forms of the illnesses (late infantile, early juvenile, late juvenile, and adult). In younger persons (under age 6 years), motor manifestations with or without cognitive impairment were common, whereas in late juvenile and adult forms, cognitive symptoms became increasingly common. Patients with earlier disease onset experienced more rapid progression. Dr. Michell-Robinson and Lépine hypothesize that arylsulfatase A activity (the defective enzyme in metachromatic leukodystrophy) and therefore buildup of toxic sulfatide levels might be related to the severity or progression of the illness. Because some older patients may also experience rapid declines, the investigators do not believe sulfatide toxicity to be the primary mediator of disease severity. They also emphasize the importance of motor system involvement as a driver of neurologic deterioration. Although there is much more to understand about this condition, it is clear now that motor symptom manifestations typically precede rapid disease progression. Metachromatic leukodystrophy is a neurodegenerative condition with a variable rate of progression that warrants more systematic investigation. In their natural history study of 98 patients with metachromatic leukodystrophy, Dr. Kehrer et al. summarize the prominent symptoms and age of symptom onset according to various forms of the illnesses (late infantile, early juvenile, late juvenile, and adult). In younger persons (under age 6 years), motor manifestations with or without cognitive impairment were common, whereas in late juvenile and adult forms, cognitive symptoms became increasingly common. Patients with earlier disease onset experienced more rapid progression. Dr. Michell-Robinson and Lépine hypothesize that arylsulfatase A activity (the defective enzyme in metachromatic leukodystrophy) and therefore buildup of toxic sulfatide levels might be related to the severity or progression of the illness. Because some older patients may also experience rapid declines, the investigators do not believe sulfatide toxicity to be the primary mediator of disease severity. They also emphasize the importance of motor system involvement as a driver of neurologic deterioration. Although there is much more to understand about this condition, it is clear now that motor symptom manifestations typically precede rapid disease progression.

Juvenile form of alexander disease caused by a previously undescribed mutation in the GFAP gene. a case report

Alexander disease is a form of leukoencephalopathy caused by mutations in the GFAP gene. There are three forms of the disease: infant, juvenile and adult. We present the clinical case of a patient born in 2004 (16 years old) with a debut of the disease at the age of 4 years with complex ticks. further neurological symptoms progressed and appeared atactic gait, intention tremor by performing coordination tests, muscle hypotension, decreased tendon reflexes, nasal voices, and behavior changes.Magnetic resonance imaging revealed changes in the white matter of both frontal lobes. An analysis was made of 59 genes of the panel “Leukodystrophy/leukoencephalopathy” by the method of mass parallel sequencing on the Ion S5. A mutation of the GFAP gene (Nm_002055), 4 exon c.758C>A, p.ALA253Asp in a heterozygous state, not described in Human Gene mutation Database, was detected. The patient was confirmed to have a diagnosis of Alexander disease. According to tractography, a decrease in the number of fibers in the frontal lobes was found.The patient is currently receiving symptomatic treatment.