Dental findings<unk>  is often discovered because of an early loss of deciduous (baby or primary) teeth with the root intact. Researchers have recently documented a positive correlation between dental abnormalities and clinical phenotype. Poor dentition is also noted in adults. Laboratory testing The symptom that best characterizes<unk>  is low serum activity of alkaline phosphatase enzyme (ALP). In general, lower levels of enzyme activity correlate with more severe symptoms. The decrease in ALP activity leads to an increase in pyridoxal 5’-phosphate (PLP), which is the major form of Vitamin B6, in the blood, although tissue levels of Vitamin B6 may be unremarkable and correlates with disease severity. Urinary inorganic pyrophosphate (PPi) levels are elevated in most<unk>  patients and, although it remains only a research technique, this increase has been reported to accurately detect carriers of the disease. In addition, most patients have an increased level of urinary phosphoethanolamine (PEA) although some may not. PLP screening is preferred over PEA due to cost and sensitivity. Tests for serum tissue-non-specific ALP (sometimes referred to as TNSALP) levels are part of the standard comprehensive metabolic panel (CMP) that is used in routine exams, although bone-specific ALP testing may be indicative of disease severity. Radiography Despite patient-to-patient variability and the diversity of radiographic findings, the X-ray is diagnostic in infantile<unk> . Skeletal defects are found in nearly all patients and include hypomineralization, rachitic changes, incomplete vertebrate ossification and, occasionally, lateral bony spurs on the ulnae and fibulae. In newborns, X-rays readily distinguish<unk>  from osteogenesis imperfecta and congenital dwarfism. Some stillborn skeletons show almost no mineralization; others have marked undermineralization and severe rachitic changes. Occasionally there can be peculiar complete or partial absence of ossification in one or more vertebrae. In the skull, individual membranous bones may calcify only at their centers, making it appear that areas of the unossified calvarium have cranial sutures that are widely separated when, in fact, they are functionally closed. Small protrusions (or "tongues") of radiolucency often extend from the metaphyses into the bone shaft. In infants, radiographic features of<unk>  are striking, though generally less severe than those found in perinatal<unk> . In some newly diagnosed patients, there is an abrupt transition from relatively normal-appearing diaphyses to uncalcified metaphases, suggesting an abrupt metabolic change has occurred. Serial radiography studies can reveal the persistence of impaired skeletal mineralization (i.e. rickets), instances of sclerosis, and gradual generalized demineralization. In adults, X-rays may reveal bilateral femoral pseudofractures in the lateral diaphysis. These pseudofractures may remain for years, but they may not heal until they break completely or the patient receives intramedullary fixation. These patients may also experience recurrent metatarsal fractures. DXA may show abnormal bone mineral density which may correlate with disease severity, although bone mineral density in<unk>  patients may not be systemically reduced. Genetic analysis All clinical sub-types of<unk>  have been traced to genetic mutations in the gene encoding TNSALP, which is localized on chromosome 1p36.1-34 in humans (ALPL; OMIM#171760). Approximately 388 distinct mutations have been described in the TNSALP gene. An up-to-date list of mutations is available online at The Tissue Nonspecific Alkaline Phosphatase Gene Mutations Database. About 80% of the mutations are missense mutations. The number and diversity of mutations results in highly variable phenotypic expression, and there appears to be a correlation between genotype and phenotype in<unk> ”. Mutation analysis is possible and available in 3 laboratories.
Hypophosphatasia
Hypoprolactinemia
Hypervalinemia
Osteomalacia
Hyperphosphatasia with mental retardation syndrome
Hyperprolinemia
Methaemalbuminaemia
Hypophosphatemia