Rare Ophthalmology News

Disease Profile

Hurler syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

E76.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Mucopolysaccharidosis Ih ; MPS1-H; MPS1H;

Categories

Congenital and Genetic Diseases; Eye diseases; Heart Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 93473

Definition
Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS1; see this term), a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy.

Epidemiology
The prevalence of the Hurler subtype of MPS1 is estimated at 1/200,000 in Europe.

Clinical description
Patients present within the first year of life with musculoskeletal alterations including short stature, dysostosis multiplex, thoracic-lumbar kyphosis, progressive coarsening of the facial features (including large head with bulging frontal bones, depressed nasal bridge with broad nasal tip and anteverted nostrils, full cheeks and enlarged lips), cardiomyopathy and valvular abnormalities, neurosensorial hearing loss, enlarged tonsils and adenoids, and nasal secretion. Developmental delay is usually observed between 12 and 24 months of life and is primarily in the realm of speech with progressive cognitive and sensorial deterioration. Hydrocephaly can occur after the age of two. Diffuse corneal compromise leading to corneal opacity becomes detectable from three years of age onwards. Other manifestations include organomegaly, hernias and hirsutism.

Etiology
Hurler syndrome is caused by mutations in the IDUAgene (4p16.3) leading to a complete deficiency in the alpha-L-iduronidase enzyme and lysosomal accumulation of dermatan sulfate and heparan sulfate.

Diagnostic methods
Early diagnosis is difficult as the first clinical manifestations are not specific. Diagnosis is based on detection of increased urinary excretion of heparan and dermatan sulfate and confirmed by demonstration of enzymatic deficiency in leukocytes or fibroblasts. Genetic testing is available.

Differential diagnosis
Differential diagnoses include the milder form of mucopolysaccharidosis type 1, the Hurler-Scheie syndrome (see this term), although this form is associated with only slight cognitive impairment. Differential diagnoses also include mucopolysaccharidosis type 6 and type 2 and mucolipidosis type 2 (see these terms).

Antenatal diagnosis
Antenatal diagnosis is possible by measurement of enzymatic activity in cultivated chorionic villus or amniocytes and by genetic testing if the disease-causing mutation is known.

Genetic counseling
Transmission is autosomal recessive. Genetic counseling and testing should be offered to couples with a positive family history.

Management and treatment
Management is multidisciplinary. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with Hurler syndrome under 2.5 years of age (and in selected patients over this age limit) as it can prolong survival, preserve neurocognition, and ameliorate some somatic features. HSCT should be performed early in the disease course, before developmental deterioration begins. Enzyme replacement therapy (ERT) with laronidase is recommended for all Hurler patients and is a lifelong therapy which alleviates non neurological symptoms. The early use of ERT has been shown to delay or even prevent the development of some of the clinical features of this condition. Additional management of Hurler syndrome is largely supportive, and includes surgical interventions (e.g. adenotonsillectomy, hernia repair, ventriculoperitoneal shunt, cardiac valve replacement, carpal tunnel release, spinal decompression); physical, occupational, and speech therapies; respiratory support (e.g., continuous positive pressure ventilation with oxygen supplementation); hearing aids; and medications for pain and gastrointestinal disturbances.

Prognosis
Patients often succumb to the condition in the first decade from respiratory and cardiac complications but ERT and HSCT can improve life expectancy. The timing of diagnosis, and therefore of treatment initiation, is an important factor for the success of both HSCT and laronidase.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal heart valve morphology
0001654
Abnormal vertebral morphology
0003468
Abnormality of the tonsils
0100765
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Cardiomyopathy
Disease of the heart muscle
0001638
Cerebral palsy
0100021
Coarse facial features
Coarse facial appearance
0000280
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Frontal bossing
0002007
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Generalized hirsutism
Excessive hairiness over body
0002230
Global developmental delay
0001263
Hepatomegaly
Enlarged liver
0002240
Hernia
0100790
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Large face
Big face
0100729
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Mucopolysacchariduria
0008155
Muscular hypotonia
Low or weak muscle tone
0001252
Rhinitis
Nasal inflammation
0012384
Short neck
Decreased length of neck
0000470
Skeletal dysplasia
0002652
Splenomegaly
Increased spleen size
0001744
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
30%-79% of people have these symptoms
Abnormal clavicle morphology
Abnormal collarbone
0000889
Abnormal diaphysis morphology
Abnormal shape of shaft of long bone
Abnormality of shaft of long bone of the limbs

[ more ]

0000940
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Abnormality of the elbow
Abnormality of the elbows
0009811
Abnormality of the ribs
Rib abnormalities
0000772
Camptodactyly of finger
Permanent flexion of the finger
0100490
Chronic diarrhea
0002028
Corneal opacity
0007957
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Depressivity
Depression
0000716
Dolichocephaly
Long, narrow head
Tall and narrow skull

[ more ]

0000268
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Glaucoma
0000501
Hearing impairment
Hearing defect
Deafness

[ more ]

0000365
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypertension
0000822
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Narrow pelvis bone
0003275
Recurrent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
Frequent respiratory infections

[ more ]

0002205
Retinopathy
Noninflammatory retina disease
0000488
Scoliosis
0002650
Short stature
Decreased body height
Small stature

[ more ]

0004322
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Thick vermilion border
Full lips
Increased volume of lip
Plump lips
Prominent lips
Thick lips

[ more ]

0012471
5%-29% of people have these symptoms
Abnormal nerve conduction velocity
0040129
Abnormal pyramidal sign
0007256
Abnormality of skin pigmentation
Abnormal pigmentation
Abnormal skin color
Abnormal skin pigmentation
Abnormality of pigmentation
Pigmentary changes
Pigmentary skin changes
Pigmentation anomaly

[ more ]

0001000
Angina pectoris
0001681
Endocardial fibroelastosis
0001706
Retinal degeneration
Retina degeneration

Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

Rare Ophthalmology News