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BabyScreen+ newborn screening

Gene: ALPL

Green List (high evidence)

ALPL (alkaline phosphatase, liver/bone/kidney)
EnsemblGeneIds (GRCh38): ENSG00000162551
EnsemblGeneIds (GRCh37): ENSG00000162551
OMIM: 171760, Gene2Phenotype
ALPL is in 19 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Well established gene-disease association.

Clinical signs of the infantile form appear during the first 6 months of life and has high mortality, with 50% succumbing to respiratory failure due to undermineralization of the ribs. The childhood form in most cases presents after the first 6 months of life and before 5 years.

Adult HP presents during middle age, though the patient may have had mild rickets in childhood. Prognosis depends on clinical course and severity. Patients with adult or odonto-HP are believed to have a normal lifespan. AD/AR inheritance reported for these milder forms.

Treatment:
TNSALP ERT has received FDA approval in three settings: perinatal, infantile, and juvenile onset HP. However, the long-term effects of treatment are not fully known. In two prospective, single-arm studies, 68 individuals with severe, perinatal/infantile HP completed 24-weeks of ERT beginning at age 1 day – 78 months. Of patients requiring respiratory support (n = 26), 81% (n = 21) survived through the last date of assessment (median age 3.2 years) versus a 5% survival rate in historical controls. Further, 54 required mechanical ventilation and of these, 91% survived and 85% were ventilator free at last contact, in comparison to 27% overall survival and 25% ventilator free in 48 historical controls. Radiographs from 64 of these individuals indicated improvement on the Radiographic Global Impression of Change (RGI-C) scale (defined as “responders”) in 74% at last assessment, though comparative historical data does not exist. Eighteen individuals with perinatal/infantile HP experienced fractures during treatment; the effect of ERT on fractures remains unclear. In a prospective open-label, single arm study, 8 patients with juvenile HP completed at least 48 months of therapy and were compared to 32 historical controls. By the RGI-C rating of radiographs, all eight patients were deemed responders; two (6%) of the historical controls were rated responders. Gait also improved in patients treated with ERT, with a 6-minute walk test improving to the normal range in six of six patients assessed by month 48, from none at baseline. The data are at present are insufficient to assess the effect of ERT on fractures in juvenile HP. The long-term effects of treatment are not fully known.

Treatment with bisphosphonates, commonly used for rickets, may be detrimental.
Created: 21 Sep 2022, 1:28 a.m. | Last Modified: 21 Sep 2022, 1:28 a.m.
Panel Version: 0.81

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypophosphatasia, childhood OMIM#241510; Hypophosphatasia, infantile OMIM#241500

Publications

History Filter Activity

23 Nov 2022, Gel status: 3

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag skeletal tag was added to gene: ALPL.

21 Sep 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: alpl has been classified as Green List (High Evidence).

21 Sep 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: ALPL were changed from Hypophosphatasia, MIM#241500 to Hypophosphatasia, childhood OMIM#241510; Hypophosphatasia, infantile OMIM#241500

21 Sep 2022, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: ALPL were set to

21 Sep 2022, Gel status: 3

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag treatable tag was added to gene: ALPL.

18 Sep 2022, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: ALPL was added gene: ALPL was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: ALPL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ALPL were set to Hypophosphatasia, MIM#241500