Mucopolysaccharidosis type 1H (MPS1H), also known as Hurler syndrome, Hurler's disease or gargoylism, is the most severe form of mucopolysaccharidosis type 1.
MPS1H presents as a multisystem disorder in the early childhood . Most important manifestation is developmental delay which becomes evident by the end of first year of life. There is also progressive mental deterioration. The systemic manifestations are classified as:
- Facial dysmorphism: There is coarsening of facial features which is usually evident at 3 to 6 months of age. Head is enlarged with frontal bossing and scaphocephalic skull due to premature closure of cranial sutures. A large mouth with thick lips may also be present. There is slight protrusion of the eyes.
- Corneal clouding: There is ground glass appearance of the cornea due to corneal clouding which may begin during the first year of life. It may lead to blindness. Degeneration of the retina is also common.
- Visceral involvement: There is progressive hepatosplenomegaly but organ dysfunction is not present. Inguinal and umbilical hernias may also occur either at birth or may develop later.
- Skeletal involvement: Skeletal abnormalities include widening of the ribs and other bone malformations. They become clinically evident at the age of 10 to 14 months. In patients with severe disease, dorsolumbar kyphoscoliosis may also be present. There is also deformity of the pelvis, femur, and clavicles. Patients with MPS1H are usually short-statured .
- Joint stiffness: Joint stiffness occurs by the age of 2 years and is progressive. There is a characteristic claw-hand deformity due to phalangial dysostosis. A common complication in these patients is carpal tunnel syndrome as a result of thickening of flexor retinaculum.
- Cardiopulmonary: Cardiopulmonary manifestations include aortic valve dysfunction and frequent upper and lower respiratory tract infections. Enlargement of tonsils and adenoids cause respiratory obstruction. In addition, there is chronic hearing loss and tongue enlargement.
- Developmental: Developmental delay occurs in children with MPS1H which usually manifests by the age of 12 to 24 months. Maximum functional age of these patients is 2 to 4 years.
- Others: Other features may include short neck, subluxation of vertebral bodies, thick and coarse body hair and thickened skin.
Entire Body System
- Short Stature
Clinical features and disease severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities and facial dysmorphism. [news-medical.net]
Other causes of general learning disability and short stature. Investigations [ 1, 3 ] Diagnosis: The urine GAGs pattern, confirmed by iduronidase enzyme assay, is diagnostic. [patient.info]
The severe form of MPS I is known as Hurler syndrome or MPS I H : Children affected with the severe form may have mental retardation, short stature, stiff joints, speech and hearing impairment, heart disease, and a shortened lifespan. [rarediseases.about.com]
Abnormalities +++ ++ Carpal Tunnel Syndrome +++ ++ Cardiac (Valvular) Disease +++ ++ Recurrent Ear, Nose, and Throat Infections +++ + Obstructive Airway Disease/Sleep Apnea +++ + Corneal Clouding +++ ++ Spinal Cord Compression +++ + Hepatosplenomegaly/Splenomegaly [mps1disease.com]
[…] the following findings in individuals with Hurler syndrome  : Coarse facial features (86.4%) Corneal clouding (70.9%) Heaptomegaly (70.0%) Kyphosis/gibbus (70.0%) Hernias (58.9%) Airway-related symptoms, such as sleep disturbances/snoring (51.6%) Splenomegaly [oncofertility.northwestern.edu]
- Failure to Thrive
[…] to thrive, intellectual disability, and developmental delay.[ 5 12 ] The extensive storage of these glycosaminoglycans is also known to cause meningeal thickening.[ 4 ] Intraoperatively, our patient was noted to have thickened arachnoid membrane, which [surgicalneurologyint.com]
Jaw & Teeth
[…] have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," an enlarged liver and spleen (hepatosplenomegaly), and a large tongue (macroglossia [ghr.nlm.nih.gov]
[…] epiglottis, a deep cranial fossa that narrows nasopharynx, hypoplastic mandible, ankylosis of temporomandibular joint, infiltration of pharyngeal tissues and tracheal cartilages, intraluminal narrowing of the conductive airways and excessive secretions, macroglossia [joacp.org]
This is especially true for patients affected by MPS as a result of reduced mouth opening, macroglossia, and frequent short and stiff cervical spine. [ijponline.biomedcentral.com]
Direct laryngoscopy evidenced in 5 out of 19 patients macroglossia, oropharyngeal and supraglottis redundant tissue, thickened epiglottis, and reduced tracheal and bronchial diameter. [hindawi.com]
Physical characteristics that may have contributed to feeding difficulties included macroglossia ( n = 13; 29.5%), and palate abnormalities ( n = 9; 20.5%). Ten patients (22.7%) had gingival hypertrophy. [ojrd.biomedcentral.com]
Liver, Gall & Pancreas
Joint stiffness, corneal clouding, umbilical hernia, abnormal facies, hepatomegaly, joint contractures, and cervical myelopathy occur. Death tends to be in their 20s. [patient.info]
In these patients ERT has been shown to improve quality of life and ameliorate hepatomegaly, apnea, joint restrictions, and other somatic symptoms [ 3 – 5 ]. [ojrd.biomedcentral.com]
Ultrasound of the abdomen revealed hepatomegaly with fatty infiltration and umbilical hernia with bowel loops and omentum as contents. Echocardiogram showed mitral valve prolapse with moderate mitral regurgitation. [joacp.org]
Abnormal enlargement of the liver (hepatomegaly), is often observed in association with a protruding abdomen in infants with I-cell disease. [rarediseases.org]
- Hearing Impairment
This increased accumulation, in time, leaves the child with various physical and neurological disabilities as well as severe mental impairment, loss of hearing, and potential blindness. [medigoo.com]
Surgical incision in the eardrum can correct hearing impairment. In order to avoid complications, surgery has also been recommended for all inguinal hernias. Ear infections caused by pharyngeal tonsils needs to be excised for better outcomes. [patienthelp.org]
Hearing impairment. Umbilical hernias and inguinal hernias. Joint stiffness and skeletal deformities. Cardiomyopathy and coronary heart disease. Hepatosplenomegaly. [patient.info]
Affected individuals exhibit severe mental retardation, clouding of the corners of the eyes, deafness, hirsutism (hairiness), enlarged liver and spleen, dwarfism with hunched back, short limbs and clawed hands, a large head with wide-set eyes, heavy brow [britannica.com]
Other manifestations include organomegaly, hernias and hirsutism. [orpha.net]
Other findings included sacral dimples ( n = 8), Mongolian spots ( n = 7), hirsutism ( n = 6), hemangiomas ( n = 3), and café au lait spots ( n = 1). Neuromuscular manifestations Most patients presented with neuromuscular abnormalities. [ojrd.biomedcentral.com]
- Coxa Valga
The epiphyseal centers are not well developed, the pelvis is poorly formed with small femoral heads and coxa valga. The clavicles are short, thick and irregular and the ribs are oar shaped. Phalanges are shortened and trapezoidal in shape. [themedicalbiochemistrypage.org]
The major joints show limitation of movement and deformities develop in flexion at the hips and knees with deformities like coxa valga, genu valgum and pes planovalgus. [medcaretips.com]
valga, dysplastic femoral epiphysis), and knee (genu valgum) . [ijponline.biomedcentral.com]
- Joint Deformity
There is also deformity of the pelvis, femur, and clavicles. Patients with MPS1H are usually short-statured. Joint stiffness: Joint stiffness occurs by the age of 2 years and is progressive. [symptoma.com]
Some individuals with MPS I have short stature and joint deformities (contractures) that affect mobility. Most people with the severe form of the disorder also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. [ghr.nlm.nih.gov]
Face, Head & Neck
- Short Neck
Head and neck findings included short neck with limited movement, macrocephaly, coarse facial features, depressed nasal bridge [Figure 1] with copious oral secretions and flexion deformity seen at elbows, wrists and knee joints. [joacp.org]
Others: Other features may include short neck, subluxation of vertebral bodies, thick and coarse body hair and thickened skin. MPS1H is a genetic disease which can be diagnosed either in the prenatal period or after the birth of the baby. [symptoma.com]
Hurler patients have a short neck and odontoid hypoplasia (decreased ossification of the odontoid bone which is the anterior process of the second vertebra). [themedicalbiochemistrypage.org]
- Low Forehead
Facial characteristics include a low forehead and enlargement of the head, sometimes resulting from hydrocephalus. Corneal clouding is common, and the neck is short. [medical-dictionary.thefreedictionary.com]
- Claw Hand Deformity
There is a characteristic claw-hand deformity due to phalangial dysostosis. A common complication in these patients is carpal tunnel syndrome as a result of thickening of flexor retinaculum. [symptoma.com]
Progressive bone and joint disease (termed dysostosis multiplex) is seen in all MPS I children and leads to All joints becoming stiff The fingers becoming stiff leading to a “claw hand deformity” Stiffness of the hips Knocked knees also known as “valgus [rarediseases.org]
MPS1H is a genetic disease which can be diagnosed either in the prenatal period or after the birth of the baby. A number of laboratory, as well as radiological investigations, are helpful to determine the diagnosis of the disease.
- Laboratory investigations: The laboratory workup consists of an examination of lymphocytes in blood smear for abnormal cytoplasmic inclusions as well as enzyme levels of L-iduronidase in cultured fibroblasts and leukocytes. Urinary levels of dermatin sulfate and heparin sulfate are also measured.
- Prenatal diagnosis: Prenatal diagnosis is established by measuring enzyme levels in amniotic cells or chorionic villi cells.
- Radiology: Radiography of the skeleton showing gibbus deformity of the lower spine and characteristic dysostosis of bones. Echocardiography is done to detect heart valve abnormalities.
Treatment of MPS1H involves palliative and curative elements . Enzyme replacement therapy with L-iduronidase is helpful in improving pulmonary function  . The walking ability of the person is also improved. In addition, it reduces the carbohydrate storage in organs .
In patients with hand, foot and joint deformities, surgical treatment is quite helpful in correcting the abnormality . Corneal clouding can be treated by corneal transplant. Some studies have shown decreased corneal opacity and improved vision even with enzyme replacement therapy .
Children with MPS1H have a poor prognosis. Mostly, they develop skeletal as well as nervous system abnormalities. The organ systems may also be involved leading to organ dysfunction. Patients may die at an early age.
There are no specific etiological or causative factors for MPS1H. It is classified as one of the lysosomal storage disorders and is genetic in origin. The disease is transferred as an autosomal recessive trait which means that the affected person should have two defective copies of the IDUA gene. This gene is responsible for the synthesis of the enzyme alpha-L-iduronidase . If both the parents have a single mutated copy of the gene (i.e. both parents are unaffected carriers) there is a 25% chance in each of their children to have MPS1H.
MPS1H is a metabolic disorder in which there is abnormal accumulation of metabolites of glycosaminoglycans in different cells of the body either due to the absence or a deficiency of a specific lysosomal enzyme alpha-L-iduronidase required for the degradation of glycosaminoglycans, dermatin sulfate and heparin sulfate resulting in organ dysfunction. Genetic mutations in the IDUA gene located on chromosome 4 site 4p16.3 result in the absence or a deficiency of the enzyme and lead to the development of Hurler syndrome.
Glycosaminoglycans are essential components of the extracellular matrix, connective tissue, and joint fluid. The degradation of these macromolecules is brought about by the lysosomal enzyme alpha-L-iduronidase. This breakdown process is essential for normal tissue growth and tissue homeostasis. If there is accumulation of these compounds within the cells it causes cell, tissue and organ dysfunction. In addition, there is an increased urinary excretion of heparin sulfate and dermatin sulfate.
MPS1H is a genetic disorder. There is no preventive measure against it.
MPS1H is a genetic metabolic disorder characterized by the deficiency of a lysosomal enzyme alpha-L-iduronidase. This enzyme is responsible for the breakdown of muccopolysaccharides also known as glycosaminoglycans. The deficiency of this enzyme therefore results in the accumulation of muccopolysaccharides in the body. MPS1H is an autosomal recessive disorder that is passed from parents to offsprings. If both the parents carry the defective gene, there is a 25% chance of developing the disease in each of their children. The disease affects many systems of the body. The most common manifestations are physical and mental growth retardation in children usually by the end of first year. Death mostly occurs by the age of 10 years due to organ damage.
MPS1H is a genetic disease which occurs due to the absence or deficiency of an enzyme alpha-L-iduronidase which results in accumulation of certain substances in the body leading to organ dysfunction. The disease runs in families and is transmitted from parents to their offspring. The syndrome manifests as abnormalities in various systems of the body as skeletal and mental abnormalities, joint and bone deformities as well as heart problems. There is no specific treatment of the disease and the affected children usually have a poor prognosis.
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