The clinical features of OSTM1-associated malignant infantile osteopetrosis: A retrospective, single-center experience over one decade.

Mutation in OSTM1 give rise to the rarest and most lethal subtype of malignant infantile osteopetrosis (MIOP), and an improved understanding of OSTM1-associated MIOP would help with informed decision-making regarding symptom management and early palliative care referral. This retrospective study describes the clinical and laboratory features of patients with a genetic diagnosis of OSTM1 MIOP made between January 2011 and December 2021 in the Department of Pediatrics, Al-Adan Hospital, Kuwait. Twenty-two children had confirmed homozygous deletion in OSTM1 (13 females, nine males). Consanguinity was reported in almost all parents. 72.7% were diagnosed before the age of two months, most commonly incidentally with a high clinical suspicion. All 22 patients developed upper respiratory symptoms, hepatosplenomegaly, poor feeding, and had severe developmental delay. 80% of patients developed pain and/or irritability, and 40.9% were diagnosed with primary seizures. Bone fractures developed in 27% of patients, most likely iatrogenic, and some patients had hernia and gum abnormalities. The mean survival was 10.9 months. The clinical presentation, symptomatology, and mortality of our cohort were compared with other cases of OSTM1 MIOP identified through a comperhensive search of the PubMed database. The findings conclude that OSTM1 MIOP is a multi-systemic disease with distinct clinical features, of which neurological complications are the most severe and include nociplastic pain and irritability. Although orthopedic complications influence the trajectory of most patients with other forms of osteopetrosis, OSTM1 MIOP is driven by its neurological complications. Hence, OSTM1 should be regarded as a neurodegenerative disease with osteopetrosis as a comorbidity that warrants early palliative care referral.

Assessing the Need for Pediatric Palliative Care in the Six Arab Gulf Cooperation Council Countries.

Background: Palliative care is an essential element of universal health coverage. However, palliative care services, particularly pediatric palliative care (PPC) services, are still inadequately developed in many countries, not least members of the Gulf Cooperation Council (GCC) (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). Advocating for palliative care services requires data-driven estimates of the number of patients needing these services. Objective: To estimate the number of children living with life-threatening illnesses in the GCC countries requiring specialist and/or generalist palliative care service provision. Method: Descriptive analysis of published cross-sectional epidemiological data. Subjects were from general and age-specific populations from individual GCC countries. The quantitative data on child population and mortality were collected from 2019 primary and secondary data sources. The need for PPC was estimated using mortality, incidence, and prevalence data from the Institute for Health Metrics and the Global Cancer Observatory. Results: Our conservative analysis revealed that just under 22,000 children needed PPC in GCC countries in 2019, a minimum of 17.5 for every 10,000 children. Discussion: There is a significant need for PPC services, suggesting that the medical needs of the pediatric population are currently not being fully met. Nationwide PPC services are essential to improve the quality of life of thousands of children in GCC countries by changing policies, professional education, and providing funding to palliative programs. To our best knowledge, this is the first study to highlight the clear and urgent need for the development of PPC services in the GCC countries.

An agenda to develop Pediatric Palliative care programs to serve children with life-threatening and life-limiting conditions in the Gulf Cooperation Council countries.

Medical advances have increased the number of children living with life-threatening/life-limiting illnesses worldwide, including in Gulf Cooperation Council (GCC) countries. Pediatric palliative care (PPC) is a relatively young subspecialty that cares for children with life-threatening/life-limiting illnesses and their families. PPC aims to alleviate physical, psychological, and social distress in children with life-threatening/life-limiting illnesses and their families and improve their quality of life. PPC is an essential service that should be implemented in all nations, as it is a human right. Moreover, a core value of PPC services is to alleviate children's suffering, irrespective of cure availability. Hence, the global consensus on palliative services must be universal and include developing countries with limited resources. While PPC services are growing internationally, the GCC countries have yet to implement these valuable services in the region. This work aims to define the local base information important to facilitating the PPC program. We explored and identified the information vital for establishing a successful program, which was then categorized and mapped into subgroups. In doing so, we outline a roadmap to facilitate the smooth introduction of PPC in GCC countries to benefit the lives of children with life-limiting illnesses.

Managing challenging pain and irritability in OSTM1 mutation-related 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.