Objective: To retrospectively analysely the electrophysiological and imaging features of isolated congenital anosmia (ICA) and to assess the clinical phenotypic characteristics and classification of ICA. Methods: Clinical data of 30 ICA patients in Beijing Anzhen Hospital from 2012 to 2019 was retrospectively reviewed, including 13 males and 17 females, aged (35±19) years. The control group consisted of 30 healthy people from medical examination center, including 13 males and 17 females, aged (39±14) years. The clinical characteristics of ICA were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), trigeminal event-related potentials (tERP) and olfactory pathway MRI. SPSS 17.0 software was used to compare the difference of olfactory function between the two groups. The correlation between olfactory bulb, olfactory sulcus structure and age was observed, and the clinical phenotype characteristics of ICA patients were analyzed. Results: The subjective olfactory function was completely lost in ICA patients. oERP was absent in all of the ICA patients, but showed normal N₁ and P₂ waves in controls. tERP could be evoked in 63.3% (19/30) of ICA patients, and signals in these patients showed higher amplitude in the N₁ ((-10.33±6.93) μV vs (-5.11±2.71) μV, t=-10.113, P<0.01) and P₂ ((+17.25±8.51) μV vs (+7.31±3.46) μV, t=5.443, P<0.01) waves than that of the controls. Olfactory bulbs were aplastic in 80.0% (24/30) of patients and hypoplastic in 20.0% (6/30) of patients. Fifty-six point seven percent (17/30) of patients had bilateral olfactory sulcus deletion while 43.3% (13/30) had dysplasia, and all of the patients exhibited a depth of olfactory sulcus less than 8 mm. Both the structure of olfactory bulbs and olfactory sulcus were not associated with age for ICA patients (r value was -0.174 and 0.325, respectively, all P>0.05). Conclusions: ICA patients show neurophysiologic deficits and some anatomic differences compared with healthy controls. The absence of oERP combining with a depth of olfactory sulcus less than 8 mm is the important indicator for clinical diagnosis of ICA. The structure of olfactory bulb may be a critical factor for clinical classification of ICA.
Adolescent ; Adult ; Anosmia ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Olfaction Disorders/diagnosis* ; Olfactory Bulb/diagnostic imaging* ; Olfactory Pathways ; Retrospective Studies ; Smell ; Young Adult

In addition to acute respiratory symptoms,coronavirus disease 2019(COVID-19)could cause olfactory dysfunction,which becomes the only clinical manifestation of COVID-19 in some cases.We review the epidemiological characteristics,pathological mechanism,screening value,treatment and prognosis of olfactory dysfunction in patients with COVID-19,aiming to achieve an in-depth understanding of the early diagnosis,quarantine,scientific treatment and prognosis of COVID-19.
COVID-19 ; Early Diagnosis ; Humans ; Olfaction Disorders/etiology* ; SARS-CoV-2 ; Smell

Mutations in the CHD7 gene, encoding for the chromodomain helicase DNA-binding protein 7, are found in approximately 60% of individuals with CHARGE syndrome (coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities and/or hearing loss). Herein, we present a clinical case of a 14-year-old male presenting for evaluation of poor growth and pubertal delay highlighting the diagnostic challenges of CHARGE syndrome. The patient was born full term and underwent surgery at 5 days of life for bilateral choanal atresia. Developmental milestones were normally achieved. At age 14 his height and weight were
Adolescent ; CHARGE Syndrome ; Choanal Atresia ; Diagnosis ; Ear ; Follicle Stimulating Hormone ; Follow-Up Studies ; Genetic Testing ; Gonadotropins ; Growth and Development ; Hearing ; Heart ; Humans ; Luteinizing Hormone ; Male ; Olfaction Disorders ; Puberty, Delayed ; Testis ; Testosterone

BACKGROUND: The olfactory bulb is anatomically exposed and thus can be directly damaged by external stimulation. This can occur as an occupational injury owing to contact with organic solvents or other causes. We present cases of eight patients who sustained occupation-related exposure to potentially toxic substances and later presented with signs and symptoms of anosmia. We examined the occupational and medical characteristics of the patients and evaluated their work-relatedness. CASE PRESENTATION: Case 1: A 50-year-old man performed high-frequency heat treatments for approximately 11 years. He experienced decreased senses for olfaction and taste during the later years culminating in the diagnosis of anosmia after 3 years (high work-relatedness). Case 2: A 54-year-old man whose work involved exposure to various organic solvents, such as spray painting and application of paint and thinners for approximately 4 years, was subsequently diagnosed with anosmia based on rhinorrhea, headache, and loss of olfaction (high work-relatedness). Case 3: A 44-year-old-man who performed spray painting for approximately 17 years developed anosmia (high work-relatedness). Case 4: A 44-year-old man was involved in ship engine cleaning once a month, for approximately 7 h per cleaning session; he was diagnosed with anosmia based on loss of olfaction (low work-relatedness). Case 5: A 41-year-old man worked in ship building block construction for approximately 13 years; anosmia diagnosis was based on loss of olfaction (low work-relatedness). Case 6: A 47-year-old woman performed product inspection and labeling at a plant manufacturing automobile parts; anosmia diagnosis was based on decreased olfaction and taste (low work-relatedness). Case 7: A 50-year-old woman performed epoxy coating in a plant manufacturing automobile parts; anosmia diagnosis was based on diminishing olfaction (low work-relatedness). Case 8: A 57-year-old woman performed cleaning of the area where mobile phone parts were manufactured; anosmia diagnosis was based on diminishing olfaction (low work-relatedness). CONCLUSION: The study results confirmed work-relatedness when the subject was young, and the duration of exposure was long without any other cause of anosmia. Regarding compensation for occupational diseases, work-relatedness can be recognized as a relative concept.
Adult ; Automobiles ; Cell Phones ; Compensation and Redress ; Diagnosis ; Female ; Headache ; Hot Temperature ; Humans ; Middle Aged ; Occupational Diseases ; Occupational Injuries ; Olfaction Disorders ; Olfactory Bulb ; Paint ; Paintings ; Plants ; Ships ; Smell ; Solvents

Subfrontal schwannomas are rarely reported. They are usually found only in the subfrontal area, but some extend to the nasal cavity. In these cases, prevention of postoperative cerebrospinal fluid (CSF) leakage through thinned or eroded anterior skull base is important. A 51-year-old female with anosmia and mild nausea was diagnosed as subfrontal extraaxial mass with nasal cavity extension. This mass was initially thought to be an olfactory groove meningioma. We performed a bifrontal craniotomy for surgical excision. We did not totally remove the tumor, as we wanted to prevent a skull base defect. The histopathological diagnosis was a schwannoma. There was no postoperative complication such as CSF leakage. The residual tumor was treated with gamma knife radiosurgery. The nasal cavity mass has not grown as of five years after radiosurgery.
Cerebrospinal Fluid ; Cerebrospinal Fluid Leak ; Craniotomy ; Cytochrome P-450 CYP1A1 ; Diagnosis ; Female ; Humans ; Meningioma ; Middle Aged ; Nasal Cavity* ; Nausea ; Neoplasm, Residual ; Neurilemmoma* ; Olfaction Disorders ; Olfactory Nerve ; Postoperative Complications ; Radiosurgery* ; Skull Base

The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime.
Adolescent ; Counseling ; Diagnosis ; Ear ; Genetic Testing ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Heart ; Humans ; Hypogonadism* ; Infertility ; Kallmann Syndrome* ; Kidney ; Mental Competency ; Neurosecretory Systems ; Olfaction Disorders ; Phenotype ; Puberty ; Sequence Analysis, DNA ; Sexual Maturation ; Signal Transduction ; Skeleton ; Smell ; Axis, Cervical Vertebra

PURPOSE: Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is classified as Kallmann syndrome (KS) with anosmia and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). This study was undertaken to investigate the clinical, endocrinological, and molecular characteristics in Korean patients with KS and nIHH. METHODS: Twenty-six patients from 25 unrelated families were included. Their clinical, endocrinological, and radiological findings were analyzed retrospectively. Mutation analysis of the GNRH1, GNRHR, KISS1, KISS1R, PROK2, PROKR2, TAC3, TACR3, FGF8, FGFR1, and KAL1 genes was performed in all patients. CHD7 and SOX10 were analyzed in patients with CHARGE (Coloboma, Heart defects, choanae Atresia, Growth retardation, Genitourinary abnormality, Ear abnormality) features or deafness. RESULTS: Of the 26 patients, 16 had KS and 10 had nIHH. At diagnosis, mean chronologic age was 18.1 years in males and 18.0 years in females; height SDS were -0.67+/-1.35 in males, -1.12+/-1.86 in females; testis volume was 2.0+/-1.3 mL; and Tanner stage was 1.5. There were associated anomalies in some of the KS patients: hearing loss (n=6) and congenital heart disease (n=4). Absence or hypoplasia of the olfactory bulb/sulci was found in 84.62% of patients with KS. Molecular defects in KAL1, SOX10, and CHD7 were identified in 5 patients from 4 families (16.0%, 4/25 pedigrees). After sex hormone replacement therapy, there were improvement in sexual characteristics and the sexual function. CONCLUSION: This study described the clinical, endocrinological, and molecular genetic features in IGD patients in Korea. Although the mutation screening was performed in 10 genes that cause IGD, molecular defects were identified in relatively small proportions of the cohort.
Cohort Studies ; Deafness ; Diagnosis ; Ear ; Female ; Gonadotropin-Releasing Hormone ; Hearing Loss ; Heart ; Heart Defects, Congenital ; Hormone Replacement Therapy ; Humans ; Hypogonadism* ; Immunoglobulin D ; Kallmann Syndrome* ; Korea ; Male ; Mass Screening ; Molecular Biology ; Nasopharynx ; Olfaction Disorders ; Retrospective Studies ; Testis ; Urogenital Abnormalities

OBJECTIVE: To analyze the relationship between olfactory bulb (OB) volume, depth of olfactory sulcus (OS) and olfactory function in patients with Alzheimer' disease (AD). METHOD: Fifty patients with AD patients and 50 healthy subjects were examined by olfactory function T&T testing, OB volume and depth of OS assessed with Magnetic resonance imaging (MRI). RESULT: T&T olfactory testing revealed that AD patients had higher scores than control group (1.50 ± 0.17, 2.80 ± 0.31, P < 0.05). Bilateral and average OB volumes were smaller in AD group [(29.78 ± 5.17) mm3, (30.14 ± 4.87)mm3, (30.05 ± 5.08) mm3] than in control group [(36.65 ± 4.08)mm3, (36.56 ± 4.12)mm3, (36.46 ± 4.11)mm3] (P < 0.01). OS depth study revealed no statistical difference between AD patients and control groups (P > 0.05). Olfactory discriminate threshold was negatively correlated with average olfactory bulb volumes (r = -0. 711, P < 0.05), and was not correlated with depth of OS (r = -0.127, P > 0.05) in AD patients. CONCLUSION The OB volume were lower in AD patients as compare to controls, the depth of OS has no significant changes in AD patients; The OB volume is correlated with olfactory function, the depth of OS is no correlated with olfactory function. Cognitive impairment degree in AD patients is accordance with the lower degree olfactory function. The olfactory loss may be the earlier period and objective diagnosis indicator for AD patients.
Alzheimer Disease ; complications ; physiopathology ; Case-Control Studies ; Humans ; Magnetic Resonance Imaging ; Olfaction Disorders ; complications ; diagnosis ; Olfactory Bulb ; anatomy & histology

OBJECTIVETo summarize the clinical features of idiopathic hypogonadotropic hypogonadism (IHH) diagnosed during childhood, and detect mutations in KAL1 and FGFR1, acting as key clues for diagnoses.

METHODWe collected and analyzed clinical data of 21 cases (including demographic data, chief complaint, history of present illness, family history, physical examination, laboratory tests and imaging studies, etc.) diagnosed with IHH from December 2008 to February 2013. Polymerase chain reaction and gene sequencing was applied to detect mutations on KAL1 and FGFR1. Fifty healthy unrelated individuals were choosen as controls.

RESULTOf 21 patients with IHH, 19 were males and 2 females, they visited us initially from 8-17 years old, with an average of (13.58 ± 2.38) years old. Sixteen cases were KS patients (76%). One boy reported abnormal sense of smelling but having olfactory perfect picture on MRI; 2/19 male cases had no puberty when they were over 13-14 years old without abnormal external genitalia. 8/19 cases only had small penis, 8/19 had both of cryptorchidism and small penis, and the Case 2 also had hypospadias. One boy had cryptorchidism combined with a normal penis. Only 2 girls diagnosed as IHH who visited us because of no puberty signs when they were 13 and 16 years old, respectively. Other clinical manifestations included: one with gynecomastia, 2 had mental retardation, and one was deaf; one with high palatal arch; one with mirror-movement and one with left renal agenesis but normal renal function respectively. Laboratory tests showed that the basic testosterone (T) is low and with inappropriately low or normal gonadotropin hormones. The results of cases of standard human chorionic gonadotropin (HCG) test of 7 cases out of 19 male children's were normal (testosterone>1 100 ng/L), and another nine cases continued to complete the extended HCG test, and the testosterone levels of two of them (cases 6, 8) were still lower than 1 000 ng/L. Family history: the parents in 9/21 family had delayed puberty, involving only one parent in 6 families, involving both in 2 families and the other one was an uncle having micropenis with a child. Among these 21 cases, only one boy's father had hyposmia and his first emission age was 14-15 years. Eleven patients accompanied abnormal sense of smelling and the olfactory organ abnormalities on MRI, 4 had olfactory organ abnormalities on MRI while they had good smelling function self-reportedly. We got 15 samples (12 KS and 3 nIHH cases) to screen the mutation of KAL1 (14 exons) and FGFR1 (18 exons). A splicing mutation c.1062+1G>A in KAL1 is identified in case 17 with IHH. One novel heterozygous FGFR1 mutation, a single base deletion mutation on the exon 1 c.27delC is identified in case 14. This mutation causes the premature termination codons.

CONCLUSIONThis pilot research showed that IHH/KS diagnosis in children depends on clinical manifestation rather than gene analysis. Small penis or cryptorchidism, smelling abnormality and positive familial history may contribute to the KS/HH diagnosis. MRI of olfactory bulb acts as important proof for diagnosis of KS. Mutations in KAL1 and FGFR1 gene are not main causes of Kallmann syndrome.

Adolescent ; Child ; DNA Mutational Analysis ; Exons ; genetics ; Extracellular Matrix Proteins ; genetics ; Female ; Heterozygote ; Humans ; Hypogonadism ; diagnosis ; genetics ; Kallmann Syndrome ; genetics ; Male ; Mutation ; genetics ; Nerve Tissue Proteins ; genetics ; Olfaction Disorders ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Sexual Maturation

The sense of smell is one of the essential tools for all living things to survive. With recent increase in diseases associated with olfactory dysfunction, the evaluation of olfactory function aims to shed light on the understanding and assessment of the human olfactory system. The methods for assessing the olfactory function are largely divided into electrophysiological and psychophysical methods. The psychophysical inspections such as University of Pennsylvania Smell Identification Test (UPSIT), The Sniffin' Stick, and T & T Olfactometer are methods mostly based on questionnaires or simple apparatus. Those have been generally used in clinical and research field due to their relatively short examination time and low cost. The electrophysiological tests evaluate olfactory function based on objective measurements like biosignals and medical imaging. Compared to the psychophysical methods, they comparably have higher reliability and are possible to assess more specific diagnosis. However, the system configuration seems to be more complicated. In this paper, we review the overall evaluation methods of olfactory functions and suggest complementary points to improve conventional technologies.
Diagnosis ; Diagnostic Imaging ; Humans ; Olfaction Disorders ; Olfactometry ; Pennsylvania ; Smell* ; Surveys and Questionnaires