Clinical Biomarkers in Alpha-mannosidosis
Condition: Alpha-Mannosidosis
MeSH terms: Mannosidase Deficiency Diseases; alpha-Mannosidosis
Study type: Observational

Summary: 
      Background:

      - Alpha-mannosidosis is a rare inherited disorder. It causes problems in many organs and
      tissues of the body. It can occur in children and adults. Because there is no treatment for
      this disease, researchers want to find out more about it.

      Objective:

      - To learn more about Alpha-mannosidosis.

      Eligibility:

      - People ages 5-60 with Alpha-mannosidosis.

      Design:

        -  Participants will be recruited from patient support organizations and medical genetics
           clinics.

        -  Participants will have 3 study visits, about once a year. A final evaluation will be
           made after 3 years.

        -  Participants will have a medical history and a physical exam.

        -  Blood samples and a urine sample will be collected.

        -  Cerebrospinal fluid will be collected. A small area of the lower back will be numbed
           with medicine. A thin needle will be inserted between the spine bones. About 2
           tablespoons of spinal fluid will be removed.

        -  Brain magnetic resonance spectroscopy (MRS) scans will be done at each visit. MRS uses a
           strong magnetic field and radio waves to take pictures of chemicals in the brain with a
           scanner. The participant will lie on a table that can slide in and out of the cylinder.
           While in the scanner the participant will hear loud knocking noises. They will get
           earplugs or earmuffs to muffle the sound. Medicines might be used to keep the
           participant asleep during the MRS.

        -  Participants will have a skin biopsy at the first visit only. A small area of the
           participant s skin will be numbed. A small circle of skin will be removed with a biopsy
           tool.
    

Detailed description: 
      Alpha-mannosidosis (AMD) is an inherited lysosomal storage disorder caused by mutations in
      the LAMAN gene, which encodes lysosomal alpha-mannosidase and is characterized by
      neurodevelopmental delay, mild immune deficiency, facial and skeletal abnormalities, hearing
      impairment, intellectual disability, muscle weakness and ataxia. The progression of
      neuromuscular and skeletal deterioration is insidious, occurring over several decades,
      rendering most patients wheel-chair dependent. No consistently successful treatment is
      available. To better characterize the biochemical phenotype and natural history of this
      disorder, we will study 15 patients with AMD, ranging in age from five to 60 years, recruited
      from Departments of Biochemical Genetics and Medical Genetics at university medical centers
      mainly in the US and Canada or referred by the Intl Society for Mannosidosis & Related
      Diseases. Participants in the study will visit the NIH Clinical Center 2-3 days on an
      outpatient basis and will undergo clinical and biochemical evaluations to establish reliable
      clinical

      benchmarks and to identify cerebrospinal fluid biomarkers that could serve as candidate

      surrogate markers of treatment effect in future clinical trials. The protocol will take
      advantage of the NICHD Biomedical Mass Spectrometry Facility to generate CSF proteomic
      profiles. Patients will also undergo MR spectroscopy (under sedation/anesthesia, if
      appropriate) in order to establish the phenotypic baseline and for possible utility as a
      guide for natural history and/or treatment outcomes in future studies. If the pre-clinical
      components of this proposal prove promising, the prospect of a recombinant adeno-associated
      viral gene therapy trial involving a brain-directed (intrathecal) approach for AMD would be
      possible within 3 years.
    

Observational model: Cohort
Time perspective: Other
Keywords: Biomarkers; Alpha-Manosidosis