scholarly journals Enrichment of gene variants associated with treatable genetic disorders in psychiatric populations

2018 ◽  
Author(s):  
Venuja Sriretnakumar ◽  
Ricardo Harripaul ◽  
John B. Vincent ◽  
James L. Kennedy ◽  
Joyce So
Keyword(s):  
Psychotic Disorders ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Genetic Disorders ◽  
Acute Intermittent Porphyria ◽  
Inborn Errors ◽  
Pathogenic Variants ◽  
Niemann Pick Disease ◽  
Poor Treatment ◽  
Niemann Pick

ABSTRACTPurposeMany genetic conditions can mimic mental health disorders, with psychiatric symptoms that are difficult to treat with standard psychotropic medications. This study tests the hypothesis that psychiatric populations are enriched for pathogenic variants associated with selected treatable genetic disorders.MethodsUsing next-generation sequencing, 2046 psychiatric patients were screened for variants in genes associated with four inborn errors of metabolism (IEMs), Niemann-Pick disease type C (NPC), Wilson disease (WD), homocystinuria (HOM), and acute intermittent porphyria (AIP).ResultsAmong the 2046 cases, carrier rates of 0·83%, 0·98%, 0·20%, and 0·24% for NPC, WD, HOM, and AIP were seen respectively. An enrichment of known and likely pathogenic variants in the genes associated with NPC and AIP was found in the psychiatric cohort, and especially in schizophrenia patients.ConclusionThe results of this study support that rare genetic disease variants, such as those associated with IEMs, may contribute to the pathogenesis of psychiatric disorders. IEMs should be considered as possible causative factors for psychiatric presentations, especially in psychotic disorders, such as schizophrenia, and in the context of poor treatment response.

IN UTERO DETECTION OF FAMILIAL METABOLIC DISORDERS

PEDIATRICS ◽  
1972 ◽  
Vol 49 (3) ◽  
pp. 329-330
Author(s):  
Henry L. Nadler
Keyword(s):  
High Risk ◽  
Genetic Disorders ◽  
Genetic Defect ◽  
High Risk Patient ◽  
Common Finding ◽  
Inborn Errors ◽  
Tay Sachs Disease ◽  
Niemann Pick Disease ◽  
Niemann Pick ◽  
Effective Use

Diagnostic amniocentesis for the prenatal detection of genetic disorders has been shown to be useful to the physician in monitoring high risk pregnancies.1 The paper by Schneck, et al.2 in this issue of Pediatrics demonstrates not only the effective use of this technique for clinical management of the high-risk patient but documents its potential value for the study of the early stages of human metabolic disease. The presence of biochemical and structural alterations in cells and organs of fetuses affected with inborn errors of metabolism appears to be a common finding. Early gestational manifestations arising from the basic genetic defect have been found in Tay-Sachs disease,2-4 Niemann-Pick disease,5 Gaucher's disease,6 Pompe's disease,7 and Krabbe's disease.8

scholarly journals Generalized Lichen Nitidus in a boy with Niemann-Pick disease type B

2013 ◽  
Vol 88 (6) ◽  
pp. 977-978 ◽  
Author(s):  
Vera Barreto Teixeira ◽  
Inês Coutinho ◽  
José Carlos Cardoso ◽  
Óscar Tellhechea
Keyword(s):  
Genetic Disorders ◽  
Disease Type ◽  
Type B ◽  
Histological Findings ◽  
Inflammatory Dermatosis ◽  
Niemann Pick Disease ◽  
Niemann Pick ◽  
Pick Disease

Generalized lichen nitidus is an uncommon chronic inflammatory dermatosis with very characteristic histological findings. Its pathogenesis is still unclear; very rarely it has been associated with genetic disorders. Herein we report the case of a 12-year-old boy with Niemann-Pick disease who developed generalized lichen nitidus.

scholarly journals Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study

2013 ◽  
Vol 22 (21) ◽  
pp. 4349-4356 ◽  
Author(s):  
P. Bauer ◽  
D. J. Balding ◽  
H. H. Klunemann ◽  
D. E. J. Linden ◽  
D. S. Ory ◽  
...  
Keyword(s):  
Genetic Screening ◽  
Psychiatric Symptoms ◽  
Disease Type ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

Porphyria and dementia: a case report

2003 ◽  
Vol 20 (3) ◽  
pp. 96-99
Author(s):  
Dympna Gibbons ◽  
Anne Cullen ◽  
Malcom Garland
Keyword(s):  
Case Report ◽  
General Population ◽  
Cognitive Decline ◽  
Metabolic Disorders ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Acute Intermittent Porphyria ◽  
Cognitive State ◽  
Advanced Stage ◽  
History Of

AbstractThe porphyrias are a group of rare hereditary metabolic disorders where there is an excess formation and excretion of porphyrins or their precursors. Type IIA, acute intermittent porphyria (AIP), has an estimated prevalence of one to eight per 100,000 in the general population but is thought to have a higher prevalence in psychiatric patients. AIP can present with a variety of psychiatric symptoms, often misdiagnosed. Associated neuropathological changes including focal cerebral ischaemic lesions have been found. However, to our knowledge, no case of dementia and AIP has been described. We present the case of a 56 year old man with a five-year history of progressive cognitive decline, diagnosed with AIP at an advanced stage of dementia. Whether AIP contributed to the dementia or is a coincidental finding is unknown. However treatment of AIP in this case resulted in some improvement in the patient's cognitive state.

Acute intermittent porphyria and disturbances in amino-acid metabolism in a psychiatric in-patient population

1994 ◽  
Vol 9 (5) ◽  
pp. 249-253
Author(s):  
JCC Rijn-van den Meijdenberg ◽  
D Fekkes ◽  
JHP Wilson ◽  
L Pepplinkhuizen ◽  
WMA Verhoeven ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
Acid Metabolism ◽  
Psychiatric Patients ◽  
Acute Intermittent Porphyria ◽  
Icd 10 ◽  
Methionine Concentration ◽  
Pathogenetic Factor ◽  
Perceptual Distortions ◽  
Serine Metabolism ◽  
Chronic Psychiatric Patients

SummaryIn recent years an enhanced catabolism of serine, with or without the existence of porphyria, has been demonstrated in relation to a specific subtype of psychosis, according to ICD-10 criteria, the acute polymorphic psychosis with or without symptoms of schizophrenia. Since sensory perceptual distortions play a key role in the symptomatology, patients with this disorder are referred to as Acute Polymorphic Psychosis plus psychosensory phenomena (APP+). In a retrospective study, including a total of 140 chronic psychiatric patients, we investigated the prevalence of Acute Intermittent Porphyria (AIP) and APP+. No subjects with AIP were found. In two patients APP+ could be demonstrated, based on both clinical characteristics and positive biochemical markers, ie lowered plasma serine concentration and increased TSM-ratio (100 × Taurine (μmol/l)/Serine concentration * Methionine concentration). In three patients the psychotic disorder was suspected to be present. It is concluded that careful psychiatric diagnosing may reveal specific psychotic disorders with a distinct biological pathogenetic factor, ie a disturbed serine metabolism.

scholarly journals When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population

2021 ◽  
Author(s):  
Venuja Sriretnakumar ◽  
Ricardo Harripaul ◽  
James L. Kennedy ◽  
Joyce So
Keyword(s):  
Psychiatric Patient ◽  
Molecular Mechanisms ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Genetic Disorders ◽  
Single Gene ◽  
Genetic Diseases ◽  
Mental Illnesses ◽  
Ongoing Research ◽  
Psychiatric Population

Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is non-responsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing (NGS) of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 72 putative affected and 293 putative carriers for TGDs were identified, with known or likely pathogenic variants in 78 genes. Despite screening for only 108 genetic disorders, this study showed an approximately four-fold (4.13%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases are greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

scholarly journals Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation

2018 ◽  
Vol 59 (6) ◽  
pp. 1058-1070 ◽  
Author(s):  
William J. Griffiths ◽  
Ian Gilmore ◽  
Eylan Yutuc ◽  
Jonas Abdel-Khalik ◽  
Peter J. Crick ◽  
...  
Keyword(s):  
Bile Acids ◽  
Ex Vivo ◽  
Hydrolysis Product ◽  
Lysosomal Storage ◽  
Inborn Errors ◽  
Niemann Pick Disease ◽  
Intermediate Metabolites ◽  
Niemann Pick ◽  
Fragmentation Patterns

7-Oxocholesterol (7-OC), 5,6-epoxycholesterol (5,6-EC), and its hydrolysis product cholestane-3β,5α,6β-triol (3β,5α,6β-triol) are normally minor oxysterols in human samples; however, in disease, their levels may be greatly elevated. This is the case in plasma from patients suffering from some lysosomal storage disorders, e.g., Niemann-Pick disease type C, or the inborn errors of sterol metabolism, e.g., Smith-Lemli-Opitz syndrome and cerebrotendinous xanthomatosis. A complication in the analysis of 7-OC and 5,6-EC is that they can also be formed ex vivo from cholesterol during sample handling in air, causing confusion with molecules formed in vivo. When formed endogenously, 7-OC, 5,6-EC, and 3β,5α,6β-triol can be converted to bile acids. Here, we describe methodology based on chemical derivatization and LC/MS with multistage fragmentation (MSn) to identify the necessary intermediates in the conversion of 7-OC to 3β-hydroxy-7-oxochol-5-enoic acid and 5,6-EC and 3β,5α,6β-triol to 3β,5α,6β-trihydroxycholanoic acid. Identification of intermediate metabolites is facilitated by their unusual MSn fragmentation patterns. Semiquantitative measurements are possible, but absolute values await the synthesis of isotope-labeled standards.

Disorders of the Human Circulatory System

2019 ◽  
pp. 288-324
Keyword(s):  
Genetic Disorders ◽  
Single Gene ◽  
Circulatory System ◽  
Body Parts ◽  
Niemann Pick Disease ◽  
Antitrypsin Deficiency ◽  
Niemann Pick ◽  
Lymphatic Fluid ◽  
Pick Disease ◽  
Human Circulatory System

This chapter focuses on genetic disorders affecting the human circulatory system. Genetic disorders can occur due to a defect in a single gene or in a set of genes. The body's circulatory system is made up of the heart and blood vessels (arteries, arterioles, veins, venules, and capillaries). The system carries both blood and lymphatic fluid in two circuits: pulmonary circulation (blood through the lungs for oxygenation) and systemic circuits (from the heart to all body parts). Fourteen disorders are presented in this chapter including sickle cell disease, Gaucher Disease, chronic myeloid leukaemia, Niemann-Pick Disease, haemophilia, atherosclerosis, ataxia telangiectasia, haemoglobinuria, thalassemia, William's syndrome, porphyria, long QT syndrome, and alpha-I-antitrypsin deficiency.

Claustrum hyperintensity: a rare radiological correlate in Niemann-Pick disease

2021 ◽  
Vol 14 (1) ◽  
pp. e239630
Author(s):  
Debaleena Mukherjee ◽  
Souvik Dubey ◽  
Goutam Ganguly ◽  
Alak Pandit
Keyword(s):  
Autoimmune Encephalitis ◽  
Epilepsy Syndrome ◽  
Inborn Errors ◽  
Niemann Pick Disease ◽  
Fluid Attenuated Inversion Recovery ◽  
History Of ◽  
Vertical Supranuclear Gaze Palsy ◽  
Niemann Pick ◽  
Tract Infections ◽  
Pick Disease

A 5-year-old male child of consanguineous parentage, without any adverse perinatal history, presented with progressive cognitive regression predominantly in the language and attention domains, for 2 years. He had simultaneous pyramidal and extrapyramidal involvement, frequent generalised tonic-clonic seizures and recurrent respiratory tract infections. Examination was significant for vertical supranuclear gaze palsy, coarse facial features and splenomegaly. Given the clinical features, in the background of consanguinity and mother’s history of spontaneous pregnancy losses, inborn errors of metabolism were suspected. Following relevant investigations including tailored genetic study, Niemann-Pick disease type C (NPC) was diagnosed. Interestingly, MRI brain showed bilateral T2/fluid-attenuated inversion recovery claustrum hyperintensities, which are more commonly associated with autoimmune encephalitis and febrile infection-related epilepsy syndrome and not reported previously in NPC. Additionally, language regression as a presenting manifestation in NPC as opposed to classical dysarthria makes this case truly unique.

Niemann-Pick Type C 1 (NPC1) and NPC2 Gene Variability in Demented Patients with Evidence of Brain Amyloid Deposition

2021 ◽  
pp. 1-11
Author(s):  
Federica Sorrentino ◽  
Andrea Arighi ◽  
Maria Serpente ◽  
Beatrice Arosio ◽  
Marina Arcaro ◽  
...  
Keyword(s):  
Psychiatric Symptoms ◽  
Amyloid Β ◽  
Elderly Subjects ◽  
Targeted Next Generation Sequencing ◽  
Modifying Factors ◽  
Pathogenic Variants ◽  
Type C ◽  
Niemann Pick ◽  
Npc2 Gene ◽  
Gene Variability

Background: Variants in Niemann-Pick Type C genes (NPC1 and NPC2) have been suggested to play a role as risk or disease modifying factors for Alzheimer’s disease (AD). Objective: The aim of this study was to analyze NPC1 and NPC2 variability in demented patients with evidence of brain amyloid-β 1–42 (Aβ) deposition and to correlate genetic data with clinical phenotypes. Methods: A targeted Next Generation Sequencing panel was customized to screen NPC1, NPC2, and main genes related to neurodegenerative dementias in a cohort of 136 demented patients with cerebrospinal fluid (CSF) low Aβ levels or positive PET with Aβ tracer and 200 non-demented geriatric subjects. Results: Seven patients were carriers of NPC variants in heterozygosis. Four of them displayed pathogenic variants previously found in NPC patients and one AD patient had a novel variant. The latter was absent in 200 non-demented elderly subjects. Five of seven patients (70%) exhibited psychiatric symptoms at onset or later as compared with 43%in non-carriers (p >  0.05). Conclusion: The frequency of NPC1 and NPC2 heterozygous variants in patients with CSF evidence of Aβ deposition is higher than in the general population.

Sign in / Sign up

Export Citation Format

Share Document