Hurler syndrome, also known as mucopolysaccharidosis type I-H (MPS I-H), is a severe, inherited lysosomal storage disorder. It is caused by a deficiency of the enzyme alpha L iduronidase (IDUA). When this enzyme is missing or not working properly, glycosaminoglycans (GAGs) build up inside cells and gradually damage many organs, including the brain, skeleton, heart, lungs, liver, eyes and ears. ( NCBI )
The information on these pages is based on peer reviewed research and clinical experience, and is written for families, patients, healthcare professionals and researchers.
A B C D E G H I L M N P S T U V Airway obstruction Partial or complete narrowing of the breathing passages in the nose, throat or windpipe. In Hurler syndrome this is often caused by thickened tissues and enlarged tonsils, adenoids and tongue.
Autosomal recessive A pattern of inheritance in which a person is affected only if they inherit two non-working copies of a gene, one from each parent. Parents with one non-working copy are usually healthy carriers.
Alpha L iduronidase (IDUA) The lysosomal enzyme that is missing or very low in Hurler syndrome. It is needed to break down certain glycosaminoglycans (GAGs).
Bone marrow transplant Everyday term often used for haematopoietic stem cell transplantation (HSCT). It replaces the blood-forming cells with donor cells that can produce the missing enzyme.
Brain atrophy Loss or shrinkage of brain tissue over time. In severe MPS I-H this can occur as part of the neurodegenerative process.
Cardiomyopathy Disease of the heart muscle that can affect how well the heart pumps blood. Some people with Hurler syndrome develop thickened heart muscle.
Chondrocyte The main cell type in cartilage. Chondrocytes store GAGs in Hurler syndrome, which disrupts normal bone growth and joint function.
Cognitive decline Loss of thinking skills, such as memory, understanding and problem solving, after they have been acquired. A hallmark of untreated severe MPS I-H.
Corneal clouding Hazy appearance of the clear front surface of the eye (cornea) caused by storage of GAGs. It can reduce vision.
Dermatan sulphate One of the glycosaminoglycans (GAGs) that build up in Hurler syndrome when alpha L iduronidase is deficient.
Dysostosis multiplex Characteristic pattern of bone changes seen on X-ray in mucopolysaccharidoses, including Hurler syndrome. It involves skull, spine, ribs, pelvis and long bones.
Enzyme A protein that speeds up chemical reactions in the body. Enzymes help break down or build up molecules. Alpha L iduronidase is the enzyme missing in MPS I-H.
Enzyme replacement therapy (ERT) Treatment in which a manufactured form of the missing enzyme is given by intravenous infusion. In MPS I this is usually laronidase.
Ex vivo gene therapy Approach where cells are removed from the body, genetically modified in the laboratory to add a working gene, and then returned to the patient.
GAGs (glycosaminoglycans) Long chains of sugar molecules that are part of connective tissues, cartilage and other structures. In Hurler syndrome, dermatan sulphate and heparan sulphate are not broken down properly and build up in cells.
Gene A stretch of DNA that contains instructions for making a specific protein, such as an enzyme.
Genotype The exact genetic variants a person has in a particular gene, for example which IDUA variants are present.
Haematopoietic stem cell transplantation (HSCT) Treatment where blood-forming stem cells from a donor are given to the patient after chemotherapy. Donor cells can produce the missing enzyme and partly correct the disease.
Heparan sulphate A glycosaminoglycan that normally helps regulate cell signalling. It builds up in Hurler syndrome and can affect the brain and other organs.
Hernia Bulge of tissue through a weak area in the abdominal wall, often at the umbilicus (belly button) or groin. Common in babies with MPS I-H.
Hurler syndrome (MPS I-H) The severe form of mucopolysaccharidosis type I. It starts in infancy, progresses quickly and, without treatment, causes early death.
IDUA gene The gene that provides the instructions for making alpha L iduronidase. Disease-causing variants in IDUA lead to Hurler syndrome and other forms of MPS I.
Immunosuppression Reduction of the activity of the immune system, usually by medicines. It is used around HSCT to prevent rejection and graft versus host disease.
Laronidase Recombinant (manufactured) alpha L iduronidase used as enzyme replacement therapy (ERT) for MPS I.
Liver and spleen enlargement (hepatosplenomegaly) Increase in size of the liver and spleen due to storage of GAGs. Often detected by examination or ultrasound.
Lysosome Small structure inside cells that acts as a recycling centre. It contains enzymes that break down complex molecules. Lysosomes are where GAGs accumulate in Hurler syndrome.
Lysosomal storage disorder Group of inherited conditions in which substances build up in lysosomes because a specific enzyme is missing or not working.
MPS I (mucopolysaccharidosis type I) Inherited lysosomal storage disorder caused by deficiency of alpha L iduronidase. It includes severe (Hurler), intermediate (Hurler–Scheie) and attenuated (Scheie) forms.
Macroglossia Unusually large tongue. Common in MPS I and contributes to feeding, speech and breathing difficulties.
Multidisciplinary team (MDT) Group of different specialists who work together to manage a complex condition. In MPS I-H this typically includes metabolic physicians, transplant specialists and many organ-specific specialists.
Newborn screening Testing of babies shortly after birth, usually using a heel-prick blood spot, to detect certain serious conditions before symptoms appear. Some regions screen for MPS I.
Neurocognitive Relating to brain function and mental processes such as thinking, learning and memory.
Pathogenic variant A genetic change that is known or very likely to cause disease.
Phenotype The observable features of a condition in a person, such as symptom pattern and severity.
Progressive Worsening over time. Hurler syndrome is a progressive condition if not effectively treated.
Scheie syndrome Historically used term for the mildest form of MPS I. Now usually grouped under attenuated MPS I.
Sleep apnoea Condition where breathing repeatedly stops or becomes very shallow during sleep. In Hurler syndrome this is usually obstructive sleep apnoea due to airway narrowing.
Somatic disease Physical disease affecting the body organs and tissues, as opposed to cognitive or psychological features.
Transplant-related mortality Risk of death related to the HSCT procedure itself, including complications of chemotherapy, infection or graft versus host disease.
Urine GAGs Measurement of glycosaminoglycans in the urine. High levels support the diagnosis of MPS, although more specific tests are needed to confirm MPS I.
Valvular heart disease Disease affecting heart valves. In MPS I-H valves become thickened and may leak or obstruct blood flow.
