Managing challenging pain and irritability in OSTM1 mutation-related infantile malignant osteopetrosis

2021 ◽  
Vol 14 (5) ◽  
pp. e242498
Author(s):  
Qutaibah Alotaibi ◽  
Manjiri Dighe
Keyword(s):  
Bone Density ◽  
Conceptual Framework ◽  
Autosomal Recessive ◽  
Severe Form ◽  
Heterogeneous Group ◽  
Malignant Osteopetrosis ◽  
Underlying Mechanisms ◽  
Infantile Malignant Osteopetrosis

Osteopetrosis describes a heterogeneous group of diseases characterised by increased bone density due to impaired osteoclast. The malignant infantile autosomal recessive (MIOP) form caused by mutations in OSTM1 is the most severe form of osteopetrosis. Children with this phenotype exhibit multisystemic complications, of which the neuropathic manifestations are the most severe. Infants with MIOP may present with pain and irritability that are likely to become continuous and debilitating as the disease progresses. There is limited understanding of the aetiology and management of pain in MIOP. Here, we describe a 2 month-old infant with OSTM1 mutation-related MIOP presenting with severe irritability and pain. This case provides the opportunity to discuss the cause and management of these distressing symptoms. We also review similar cases and the possible underlying mechanisms of pain and irritability to help provide a conceptual framework for the management of these symptoms in infants with OSTM1 MIOP.

Longitudinal Follow-up of Malignant Osteopetrosis by Skeletal Radiographs and Restriction Fragment Length Polymorphism Analysis After Bone Marrow Transplantation

PEDIATRICS ◽  
1992 ◽  
Vol 90 (6) ◽  
pp. 986-989
Author(s):  
ROBERT E. SCHROEDER ◽  
F. LEONARD JOHNSON ◽  
MICHAEL J. SILBERSTEIN ◽  
WILMA L. NEUMAN ◽  
JEANNE M. HOAG ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Fragment Length Polymorphism ◽  
Autosomal Recessive Disorder ◽  
Polymorphism Analysis ◽  
Newborn Period ◽  
Normal Bone ◽  
Malignant Osteopetrosis ◽  
Osteoclast Function ◽  
Infantile Malignant Osteopetrosis

Infantile malignant osteopetrosis is a rare autosomal recessive disorder characterized by presentation in the first months of life with manifestations related to an underlying defect in osteoclast function. Abnormal osteoclast activity paired with normal bone formation by osteoblasts leads to development of densely sclerotic fragile bones. Encroachment on the marrow cavities by hyperostotic bone results in profound anemia and thrombocytopenia, with extramedullary ullary hematopoiesis and hypersplenism. Deficits in immune function can lead to presentation with overwhelming sepsis in the newborn period. Narrowing of the optic and auditory foramina can lead to progressive blindness and hearing loss. Until recently, the prognosis for this disorder had been uniformly dismal with death usually occurring within a few months.l-3

scholarly journals Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping Wu ◽  
Zhe Cai ◽  
Wen-Hui Jiang ◽  
Gen Lu ◽  
Pei-Qiong Wu ◽  
...  
Keyword(s):  
Bone Density ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
High Precision ◽  
Radiographic Examination ◽  
Mineral Density ◽  
Novel Mutations ◽  
Whole Exome ◽  
Malignant Osteopetrosis ◽  
Infantile Malignant Osteopetrosis

Abstract Background Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing. Case presentation We present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO. Conclusions To date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.

Identification of Novel Mutation in Autosomal Recessive Infantile Malignant Osteopetrosis

2013 ◽  
Vol 81 (9) ◽  
pp. 969-970 ◽  
Author(s):  
Sirisha Rani Siddaiahgari ◽  
Darshak Makadia ◽  
Nikit Shah ◽  
Radha Rama Devi ◽  
Lokesh Lingappa
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Malignant Osteopetrosis ◽  
Infantile Malignant Osteopetrosis

scholarly journals Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunyu Liu ◽  
Muhammad Ajmal ◽  
Zaineb Akram ◽  
Tariq Ghafoor ◽  
Muhammad Farhan ◽  
...  
Keyword(s):  
Molecular Diagnosis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Missense Variant ◽  
Whole Exome ◽  
Novel Variants ◽  
Malignant Osteopetrosis ◽  
The Stability ◽  
Pakistani Families ◽  
Infantile Malignant Osteopetrosis

AbstractOsteopetrosis is a genetically heterogenous, fatal bone disorder characterized by increased bone density. Globally, various genetic causes are reported for osteopetrosis with all forms of inheritance patterns. A precise molecular diagnosis is necessary for prognosis and for prescribing treatment paradigms in osteopetrosis. Here we report on thirteen individuals diagnosed with infantile malignant osteopetrosis coming from ten unrelated Pakistani families; nine of whom are consanguineous. We performed whole exome sequencing and Sanger sequencing in all families and identified homozygous variants in genes previously reported for autosomal recessive inheritance of osteopetrosis. All the identified variants are expected to affect the stability or length of gene products except one nonsynonymous missense variant. TCIRG1 was found as a candidate causal gene in majority of the families. We report six novel variants; four in TCIRG1 and one each in CLCN7 and OSTM1. Our combined findings will be helpful in molecular diagnosis and genetic counselling of patients with osteopetrosis particularly in populations with high consanguinity.

scholarly journals Osteopetro-Rickets: A Rare Paradoxical Association in an Infant

2012 ◽  
Vol 32 (1) ◽  
pp. 88-89
Author(s):  
MB Patil
Keyword(s):  
Case Report ◽  
Key Words ◽  
Bone Disease ◽  
Clinical Signs ◽  
Severe Anaemia ◽  
Management Options ◽  
Positive Balance ◽  
Malignant Osteopetrosis ◽  
Infantile Malignant Osteopetrosis ◽  
Key Words Osteopetrosis

Infantile malignant osteopetrosis is a hereditary bone disease with intense positive balance of body calcium. Osteopetro-rickets is a very rare paradoxical association of infantile osteopetrosis and rickets. This is a case report of an infant with osteopetro- rickets. He presented with severe anaemia, splenomegaly, hepatomegaly and clinical signs of rickets. The clinical, biochemical and skeletal survey showed osteopetrosis and rickets. We also describe the pathophysiologic mechanism and various management options. Key words: Osteopetrosis; Osteopetro-rickets; Rickets DOI: http://dx.doi.org/10.3126/jnps.v32i1.5292 J. Nepal Paediatr. Soc. Vol.32(1) 2012 88-89

The Home Advantage In Sport Competitions: A Literature Review

1992 ◽  
Vol 14 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Kerry S. Courneya ◽  
Albert V. Carron
Keyword(s):  
Literature Review ◽  
Conceptual Framework ◽  
Future Research ◽  
Systematic Research ◽  
Review Of Literature ◽  
Comprehensive Review ◽  
Clear Sense ◽  
Sense Of Direction ◽  
Home Advantage ◽  
Underlying Mechanisms

A home advantage in sport competitions has been well documented. The strength and consistency of the home advantage has made it a popular phenomenon in sport today. Very little systematic research has been carried out, however, and the home advantage remains one of the least understood phenomena in sport. It appears that much of the game location research has been arbitrary, and a clear sense of direction is lacking. The purpose of the present paper is to provide a conceptual framework to organize a comprehensive review of previous game location research and provide direction for future research. The review of literature indicated that the descriptive phase of inquiry has been completed, and it is time to address the underlying mechanisms responsible for the manifestation of the home advantage. Possible methodologies and areas of inquiry are highlighted and discussed.

scholarly journals Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2709 ◽  
Author(s):  
Janin Henkel ◽  
Katja Buchheim-Dieckow ◽  
José P. Castro ◽  
Thomas Laeger ◽  
Kristina Wardelmann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endurance Exercise ◽  
Weight Reduction ◽  
Dietary Intervention ◽  
Exercise Group ◽  
Severe Form ◽  
Alcoholic Fatty Liver ◽  
Male Wistar Rats ◽  
Underlying Mechanisms ◽  
The Impact

Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction. The underlying mechanisms are unclear and cannot be studied in humans. Here, a rat NAFLD model was developed that reproduces many facets of the diet-induced NAFLD in humans. The impact of endurance exercise was studied in this model. Male Wistar rats received control chow or a NASH-inducing diet rich in fat, cholesterol, and fructose. Both diet groups were subdivided into a sedentary and an endurance exercise group. Animals receiving the NASH-inducing diet gained more body weight, got glucose intolerant and developed a liver pathology with steatosis, hepatocyte hypertrophy, inflammation and fibrosis typical of NAFLD or NASH. Contrary to expectations, endurance exercise did not improve the NASH activity score and even enhanced hepatic inflammation. However, endurance exercise attenuated the hepatic cholesterol overload and the ensuing severe oxidative stress. In addition, exercise improved glucose tolerance possibly in part by induction of hepatic FGF21 production.

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