Mucolipidosis type IV: Clinicl manifestations and natural history

McGill University, Montréal, Quebec, Canada
American Journal of Medical Genetics (Impact Factor: 3.23). 12/1991; 41(3):313-8. DOI: 10.1002/ajmg.1320410310
Source: PubMed


The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.

3 Reads
  • Source
    • "Thus far, MLIV has been known to associate developmental brain abnormalities with a degenerative retinopathy [4]. The disease has currently no specific therapy and its natural history has not been determined or quantified [5] [6]. In order to design adequate future clinical trials, quantitative description of the natural history of the various aspects of MLIV needs to be obtained. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mucolipidosis type IV (MLIV) is an autosomal recessive disorder resulting from mutations in the MCOLN1 gene. This gene encodes the endosomal/lysosomal transient receptor potential channel protein mucolipin-1 (TRPML1). Affected patients suffer from neurodevelopmental abnormalities and progressive retinal dystrophy. In a prospective natural history study we hypothesized the presence of an additional slow cerebral neurodegenerative process. We have recruited 5 patients, tested their neurodevelopmental status, and measured cerebral regional volumes and white matter integrity using MRI yearly. Over a period of up to 3 years, MLIV patients remained neurologically stable. There was a trend for increased cortical and subcortical gray matter volumes, and increased ventricular size, while white matter and cerebellar volumes decreased. Mean diffusivity (MD) was increased and fractional anisotropy (FA) values were below normal in all analyzed brain regions. There was a positive correlation between motor scores of the Vineland scale and the FA values in the corticospinal tract (corr coef 0.39) and a negative correlation with the MD values (corr coef. -0.50) in the same brain region. We conclude from these initial findings that deficiency in mucolipin-1 affects the entire brain but that there might be a selective regional cerebral neurodegenerative process in MLIV. In addition, these data suggest that diffusion-weighted imaging might be a good biomarker for following patients with MLIV. Therefore, our findings may be helpful for designing of future clinical trials.
    Full-text · Article · Jan 2013 · Molecular Genetics and Metabolism
  • Source

    Preview · Article ·

  • No preview · Article · Feb 1977 · Nippon rinsho. Japanese journal of clinical medicine
Show more