Hyperphosphatasia with mental retardation syndrome, HPMRS, also known as Mabry syndrome, has been described in patients recruited on four continents world-wide. Mabry syndrome was confirmed to represent an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

syndrome characterized by severe

mental retardation Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signific ...

, considerably elevated serum levels of

alkaline phosphatase The enzyme alkaline phosphatase (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic ...

hypoplastic Hypoplasia (from Ancient Greek :wikt:ὑπό, ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...

, a broad nasal bridge and a rectangular face.

Pathogenesis

While many cases of HPMRS are caused by mutations in the

PIGV GPI mannosyltransferase 2 is an enzyme that in humans is encoded by the ''PIGV'' gene. See also *Hyperphosphatasia with mental retardation syndrome Hyperphosphatasia with mental retardation syndrome, HPMRS, also known as Mabry syndrome, has been ...

gene, there may be genetic heterogeneity in the spectrum of Mabry syndrome as a whole. PIGV is a member of the molecular pathway that synthesizes the

glycosylphosphatidylinositol Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in ...

anchor. The loss in PIGV activity results in a reduced anchoring of alkaline phosphatase to the surface membrane and an elevated alkaline phosphatase activity in the serum.

Diagnosis

The clinical diagnosis can be established if the patient has repeatedly elevated levels of alkaline phosphatase activity in the blood serum and exhibits intellectual disability. Supportive for the clinical diagnosis are

epilepsies Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

brachydactyly Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means "short finger". The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an in ...

and a characteristic facial gestalt, which can also be assessed by means of AI. The clinical diagnosis can be confirmed by molecular testing such as

exome sequencing Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome (known as the exome). It consists of two steps: the first step is to select only the subse ...

Treatment

So far, no causal treatment is available for HPMRS. A mouse model that mirroring the human phenotype has been engineered by Crispr-Cas technology and is available for compound screening.

References

External links

{{Phospholipid metabolism disorders Rare syndromes Phospholipid metabolism disorders