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About multiple sulfatase deficiency (doc 13)

What is multiple sulfatase deficiency (doc 13)?

Multiple sulfatase deficiency is a very rare hereditary metabolic disorder in which all of the known sulfatase enzymes (thought to be seven in number) are deficient or inoperative. Major symptoms include mildly coarsened facial features, deafness, and an enlarged liver and spleen (hepatosplenomegaly). Abnormalities of the skeleton may occur, such as curvature of the spine (lumbar kyphosis) and the breast bone. The skin is usually dry and scaly (ichthyosis). Before symptoms are noticeable, children with this disorder usually develop more slowly than normal. They may not learn to walk or speak as quickly as other children.

What are the symptoms for multiple sulfatase deficiency (doc 13)?

Mild infantile symptom was found in the multiple sulfatase deficiency (doc 13) condition

Classically, the subtypes of MSD are defined by the age at symptom onset: neonatal, severe late infantile, mild infantile, and juvenile. The clinical relevance of these divisions is unknown, as subtle symptoms are present in infancy across all types. Because MSD is the result of a variable degree of deficiency across all human sulfatases, the systemic symptoms can be variable.

METABOLIC

  • Metabolic acidosis-buildup of acid in body
  • Growth delays

CRANIOFACIAL

  • Coarse facial features
  • Microcephaly
  • Macrocephaly
  • Progressive hydrocephalus

Eyes

  • Corneal clouding
  • Retinopathy, retinitis pigmentosa
  • Strabismus (abnormal eye alignment)
  • Optic nerve abnormalities
  • Cataracts
  • Glaucoma

Ears

  • Hearing disorders
  • Recurrent otitis media

Mouth/oral/Jaw

  • Feeding difficulties
  • Gingival hyperplasia (overgrowth of gum tissue around the teeth)
  • Dental anomalies (abnormal enamel) and risk for dental cavities
  • Oral, pharyngeal and upper airway obstruction with progressive narrowing of airway
  • Airway obstruction
  • Abnormal tracheal structure
  • Micrognathia (small) or retrognathia (abnormal posterior position of jaw)
  • Progressive difficulty with bite, teeth, and enamel

NEUROLOGICAL

  • Global developmental delay or regression in all reported cases
  • Epilepsy/ Seizures
  • Peripheral neuropathy
  • Neuropathic pain

CARDIOVASCULAR

  • Atrial septal defects
  • Cardiac hypertrophy (enlarged heart)
  • Heart valve issues
  • Arrhythmias
  • Hypertension (high blood pressure)
  • Aortic insufficiency

RESPIRATORY

  • Aspiration
  • Recurrent pneumonia
  • Sleep issues
  • Central apnea and/or peripheral apnea
  • Lung disease (obstructive and restrictive)
  • Progressive respiratory insufficiency

DERMATOLOGIC (skin)

  • Ichthyosis- dry, thick, scaly skin
  • Hirsutism (excessive hair growth)

GASTROINTESTINAL (GI)/ URINARY

  • Poor motility- feeding intolerance, Constipation
  • Hepatosplenomegaly (liver and spleen enlargement)
  • Issues with gallbladder
  • Gastroesophageal reflux disease (GERD)
  • Swallowing difficulties
  • Gall bladder wall thickening or polyps
  • Urinary retention
  • Urinary infections
  • Neurogenic bladder

MUSCULOSKELETAL

  • Short stature
  • Broad thumbs and toes
  • Irregular ribs
  • Hypotonia or mixed tone
  • Dysostosis multiplex- abnormalities in development of skeletal cartilage and bone
  • Spasticity- persistent muscle contraction
  • Mobility issues
  • Joint stiffness and contractures of joints especially fingers, elbows and hips
  • Hip dislocation or dysplasia (abnormal growth)
  • Extreme Weakness due to neurodegeneration and demyelination
  • Osteopenia (weakened bones)
  • Spinal instability
    • Cervical spine instability
    • Neck hyperextension
  • Scoliosis and/or kyphosis

What are the causes for multiple sulfatase deficiency (doc 13)?

Multiple sulfatase deficiency is an autosomal recessive disorder caused by a change (mutation) in the SUMF1 gene. This gene allows cells to make an enzyme called FGE (formylglycine-generating enzyme) that activates all sulfatases within the cell. Without activation, sulfatases are not able to do their jobs in the cell. The missing sulfatases are directly responsible for the changes in the body seen in MSD. More severe forms of the disease are associated with SUMF1 mutations that lead to the production of an unstable form of FGE, while the more mild forms are due to mutations that lead to reduced but correctly functioning FGE.

Recessive genetic disorders like multiple sulfatase deficiency occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

What are the treatments for multiple sulfatase deficiency (doc 13)?

There are currently no targeted therapies for MSD, and treatment is supportive and based upon symptoms. Care for patients with MSD requires a multidisciplinary team to evaluate the many body systems that may be affected by this disease. Due to the very broad spectrum of clinical problems a comprehensive approach is recommended. Depending on the needs of the child, important members of the team may include neurology and/or metabolism, complex care pediatrics, gastroenterology, nutrition, urology, orthopedics, and physiatry.

The neurologic delay and regression is the most common symptom shared by patients with MSD. Early evaluation and intervention by physical, occupational, and speech therapy can be helpful to manage the symptoms of MSD and maximize mobility and communication.

What are the risk factors for multiple sulfatase deficiency (doc 13)?

Pathogenic mutations in the SUMF1 gene produce the autosomal recessive condition known as multiple sulfatase deficiency. The brain, skin, and skeleton are primarily affected by multiple sulfatase deficiency. Multiple sulfatase insufficiency has three types: neonatal, late-infantile, and juvenile due to the considerable variation in its indications and symptoms.

Risk factors for Multiple Sulfatase Deficiency

  • Despite the fact that it affects people of all races, it may be more common in those of Ashkenazi Jewish ancestry because of the presence of an existing mutation. Clinical signs often first show between the ages of one and two, but they can do so at any time.
  • Multiple sulfatase deficiency is an example of a recessive genetic condition, which develops when a person receives the same mutated gene from both parents.
  • A person will be a carrier of the disease if they have one normal gene and one Multiple Sulphate Deficiency disease gene, although they often won't develop or show any symptoms.
  • With each pregnancy, there is a 25% chance that a kid will be impacted if both parents are carriers. Each pregnancy carries a 50% chance of passing the gene to the unborn child. A child has a 25% probability of inheriting normal genes from both parents and being genetically normal for that specific trait.
  • Both men and women are at the same level of risk of Multiple Sulfatase Deficiency.


Conditions
Late infantile MSD,Mild infantile,Short life expectancy
Drugs
NA
Symptoms
Leuukodystrophy,Seizures,Developmental delay,
Slow growth,Progressive loss of mental abilities,Skeletal defect,Coarse facial features,Enlarged organs,Hearing loss

Is there a cure/medications for multiple sulfatase deficiency (doc 13)?

Multiple sulfatase deficiency (MSD), is a lysosomal storage disorder (LSD), that leads to neurological decline and mental retardation, skin abnormalities, and dysmorphism. Based on the age of onset, the disorder or condition can be divided into three subtypes: Neonatal, Late infantile, or juvenile.

Symptoms of Multiple Sulfatase Deficiency (MSD)

  • Any person with ichthyosis, coarse facial features, developmental delays, and anomalies of the bones should have MSD suspected. Examination conducted to identify the MSD:
  • When a child has elevated sulfatide levels and low levels of at least two sulfatases, MSD can be identified.
  • Glycosaminoglycan levels are one additional test that may be helpful, even if they may be normal in certain MSD patients. Molecular genetic testing for SUMF1 gene mutations can also be beneficial; however, due to the disease's rarity, only a small number of disease-causing variants have been thoroughly documented.


Cure for Multiple Sulfatase Deficiency

  • Since there are no specific treatments for Multiple Sulfatase Deficiency yet, the primary emphasis is on symptom management.
  • A multidisciplinary team must assess the various body systems that could be impacted by MSD as part of the patient's care.
  • A thorough approach is advised since clinical disorders span a very wide spectrum.
  • Important team members may include neurology and/or metabolism, complex care pediatrics, gastrointestinal, nutrition, urology, orthopedics, and physiatry, depending on the needs of the child.


Conditions
Late infantile MSD,Mild infantile,Short life expectancy
Drugs
NA
Symptoms
Leuukodystrophy,Seizures,Developmental delay,
Slow growth,Progressive loss of mental abilities,Skeletal defect,Coarse facial features,Enlarged organs,Hearing loss

Video related to multiple sulfatase deficiency (doc 13)