IDUA gene
Includes:
Hurler-Scheie syndrome – OMIM#607015 https://omim.org/entry/607015
Scheie syndrome – OMIM#607016 https://omim.org/entry/607016
1. The Disease:
Mucopolysaccharidosis I (MPS I), or Hurler syndrome, is a lysosomal storage disease leading to complete absence of the enzyme, α-L-iduronidase, causing the accumulation of dermatan sulfate and heparan sulfate.
2. The Symptoms:
Infants are initially asymptomatic at birth and in the neonatal period (except for possible inguinal or umbilical hernia), although individuals with severe MPS usually become symptomatic in the first year of life and have rapid disease progression. Lack of early signs or symptoms does not exclude the diagnosis.
- Traditionally, individuals with MPS I have been classified as having one of the following three syndromes – Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome. As there are no identifiable biochemical differences and there exists significant clinical overlap, it is now generally accepted to use a binary classification: 1) severe, and 2) attenuated to describe patients with MPS I. The age of onset and severity differ depending on the form. Individuals with severe MPS I usually develop serious signs and symptoms in the first year of life and have rapid disease progression. In the attenuated form, symptoms are generally milder and do not appear until later in childhood.
- Hernias (inguinal or umbilical) are the earliest presenting symptom in both severe and attenuated MPS I. Coarsening of facial features (including macrocephaly with bulging frontal bones, depressed nasal bridge with broad nasal tip and anteverted nostrils, full cheeks and enlarged lips) is the most prevalent early manifestation in patients with severe MPS I.
- Additional features include musculoskeletal alterations (including short stature, dysostosis multiplex, thoracic-lumbar kyphosis, cardiomyopathy and valvular abnormalities), neurosensorial hearing loss, enlarged tonsils and adenoids, and runny nose. Developmental delay is usually observed between one and two years of age. Hydrocephalus can occur after the age of two. Diffuse corneal compromise leading to corneal opacity becomes detectable from age three years and on. Other manifestations include organomegaly and hirsutism.
3. Actions to take in case of early diagnosis:
- Babies with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in the IDUA gene) should continue breastfeeding. Early treatment is essential in preventing chronic symptoms.
- Babies should have confirmatory MPS I testing through the measurement of α-L-iduronidase activity in white blood cells or dried blood spot.
- As the clinical manifestations of MPS I are multisystemic, a multidisciplinary approach is required to proactively recognize and manage complications. Routine assessment of the various affected organs is necessary, and each specialist in the multidisciplinary team should oversee continuing evaluations once a clinical problem is identified.
- Hematopoietic stem cell transplantation (HSCT) is considered an option of care for children with MPS I, depending on the age of the patient and disease burden, at the time of treatment initiation, can improve outcome.
- Enzyme replacement therapy (ERT) with laronidase is recommended for all MPS I patients that are not eligible, or who have failed, HSCT.
- As symptoms progress, surgeries (e.g., shunting for hydrocephalus, tonsillectomy and adenoidectomy, positive pressure ventilation – CPAP or tracheostomy, carpal tunnel release, cardiac valve replacement, hip replacement) may be recommended to improve quality of life.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information
Biblio:
- https://www.ncbi.nlm.nih.gov/books/NBK1162/
- Taylor M, Khan S, Stapleton M, et al. Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future. Biol Blood Marrow Transplant. 2019;25(7). PMID: 3077251