Clinical Guidance

Individuals of Ashkenazi Jewish ancestry usually have the severe form of MLIV. A pathogenic variant that creates a new preferred splice site of MCOLN1, (p.Phe454_Asn569del) was identified in a Canadian family from Newfoundland; it causes an atypical form of MLIV, in which affected individuals walk independently and have better communicative skills . Variants in the loop between the first and second transmembrane domain. Pathogenic variants found in the loop between the first and second transmembrane domain, one in the lipase domain and one eliminating one of the four cysteines in the loop, possibly reduce the stability of mucolipin-1. Individuals with these pathogenic variants had a mild phenotype, an independent ataxic gait, and the ability to use their hands to feed themselves.

Source: GeneReviews — "Mucolipidosis IV"

Diagnostic Criteria

Suggestive Findings

Mucolipidosis IV (MLIV) should be suspected in any individual with the following clinical and laboratory findings.

Clinical findings

• Early onset of developmental delay whether static, as in cerebral palsy, or progressively declining with loss of previously acquired cognitive and motor abilities

• Dystrophic retinopathy with or without corneal clouding

Laboratory findings

• Elevated plasma gastrin concentration (due to achlorhydria) in virtually all individuals with MLIV (mean: 1507 pg/mL; range: 400-4100 pg/mL; normal: 0-200 pg/mL)

• Achlorhydria

Establishing the Diagnosis

The diagnosis of MLIV is established in a proband with suggestive findings and biallelic pathogenic (and likely pathogenic) variants in MCOLN1 or (if molecular genetic testing is unavailable and/or uninformative) ...

Source: GeneReviews — "Mucolipidosis IV"

Differential Diagnosis

The earliest signs of mucolipidosis IV (MLIV) include axial hypotonia, developmental delay, and strabismus, which are nonspecific and often lead to a provisional diagnosis of cerebral palsy. However, the finding of corneal clouding in combination with these neurologic features is relatively specific and should trigger further workup for MLIV. Eye Findings Table 2. Disorders with Eye Findings of Interest in the Differential Diagnosis of Mucolipidosis IV

Management Guidelines

No clinical practice guidelines for mucolipidosis IV (MLIV) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MLIV, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Mucolipidosis IV

Source: GeneReviews — "Mucolipidosis IV"

Clinical Guidance

Chloroquine may be contraindicated, based on published research in cultured skin fibroblasts from affected individuals .

Source: GeneReviews — "Mucolipidosis IV"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Mucolipidosis IV"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with Mucolipidosis IV

Source: GeneReviews — "Mucolipidosis IV"