Practical management of lysosomal storage disorders (LSDs)

Abstract

Lysosomal Storage Disorders (LSDs) comprise a group of disorders causing defects at the organelle and suborganelle level with a wide range of pathophysiologies and clinical consequences. Signs and symptoms of LSDs involve multiple organ systems. The main pathological mechanism of most LSDs was previously thought to be cytotoxic effects of a specific storage substance secondary to functional impairment or insufficient lysosomal enzymes. Other pathophysiologic mechanisms of LSDs have been discovered such as dysfunction of cell signaling, disturbance of cell homeostasis, inflammatory process and dysfunction of autophagy. The goal of treatment is to balance equilibrium of the enzyme and the accumulated substance. Replacing deficient enzyme through exogenous enzyme replacement therapy (ERT) or stem cell transplantation has been the main method of treatment for several years. The ability of ERT to alleviate neurologic symptoms is limited owing to the inability of the exogenous enzyme to cross the blood-brain barrier. The benefit of stem cell transplantation on neurologic symptoms has been demonstrated for Hurler syndrome, but it is not clear for most LSDs. Other strategies, such as gene therapy, have been under development to overcome this limitation and provide a better outcome. Early treatment or pre-symptomatic treatment could also slow disease progression and improve prognosis. The scope of this article is to review current and new therapeutic strategies as well as disease non-specific management.

Knowledge and perception of inborn errors of metabolism (IEMs) among healthcare students at a selected public university in Klang Valley, Malaysia

“…Basic laboratory tests; such as blood or urinalysis; can be used in conjunction with clinical evaluation to obtain a differential diagnosis or confirm a diagnosis (7). Meanwhile, the long-term care and treatment of IEM patients involves collaboration of healthcare professionals from multiple disciplines; such as physicians, nurses, pharmacists, dietitians, laboratory practitioners, speech therapists, occupational therapists, dentists, and social workers (8)(9)(10)(11)(12)(13)(14). A multidisciplinary team is essential and crucial to provide IEM patients with better quality health care in terms of treatment, psychological support, and educational resources (15).…”

GM2-gangliosidosis, type I (Tay – Sachs disease) in the pediatrician practice

“…1. МРТ головного мозга пациента с инфантильной формой GM2-ганглиозидоза длинного плеча хромосомы 11 в хромосомной области 11q23-qter) [33].…”

“…Вишнево-красные пятна выявлены у 17 пациентов (68%). Возраст начала задержки моторного развития варьировал от 3 до 7 мес, наиболее часто -3-4 мес, а возраст, в котором начинался регресс психомоторных навыков, -от 6 до 10 мес [33]. У пациента, клиническое описание которого мы приводим, к 6 мес также отмечалась задержка темпов психомоторного развития, а к 8 мес -задержка психомоторного развития, однако основной жалобой родителей в возрасте 6 мес было нарушение зрения в виде отсутствия фиксации взора, а жалобы на задержку развития появились позже.…”

“…Все заболевания, с которыми проводится дифференциальная диагностика, имеют ряд сходных клинических проявлений. В первую очередь это прогрессирующая задержка психомоторного развития, регресс ранее приобретенных сначала моторных, потом психоречевых навыков, прогрессирующая утрата зрения, судорожный синдром, в большинстве случаев плохо поддающийся терапии, достаточно быстрое прогрессирование неврологической симптоматики [33,34].…”

Congenital Heart Malformations Masked by Infantile Gangliosidosis—Case Report and Growing Evidence for Metabolic Disease-Associated Aortopathies

“…However, any organ system can be affected, and the severity spectrum ranges from mild to severe. The manifestations of lysosomal diseases are due to cellular insults caused by the accumulated substrate, as well as autophagy anomalies, immune system dysfunctions, inflammatory processes, and oxidative stress [ 2 ]. The presentation of these anomalies depends on the substrate involved and the triggered cascades of intracellular and intercellular reactions.…”