[Infantile hypophosphatasia caused by a novel compound heterozygous mutation: a case report and pedigree analysis]

Area of Science:

• Genetics
• Pediatrics
• Biochemistry

Background:

• Infantile hypophosphatasia (HPP) is a rare, severe genetic disorder characterized by defective bone mineralization.
• It is caused by mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase, essential for bone metabolism.

Observation:

• A 5-month-old boy presented with severe skeletal deformities, feeding difficulties, failure to thrive, developmental delay, and respiratory complications.
• Laboratory tests revealed significantly reduced serum alkaline phosphatase activity.
• Pedigree analysis identified compound heterozygous ALPL gene mutations in the proband, inherited from his parents, and a novel pathogenic mutation (c.228delG) in his mother and aunt.

Findings:

• The proband carried a novel pathogenic ALPL gene mutation (c.228delG) and a previously reported pathogenic mutation (c.407G>A).
• His father was heterozygous for c.407G>A, his mother for c.228delG, and his aunt carried the c.228delG mutation, with mild biochemical and skeletal findings.
• This expands the known spectrum of ALPL gene mutations associated with HPP.

Implications:

• ALPL gene mutation analysis is a definitive diagnostic tool for hypophosphatasia.
• Identifying novel mutations contributes to a better understanding of HPP's genetic basis and provides a foundation for genetic counseling and diagnosis.
• This case highlights the importance of comprehensive genetic evaluation in infantile skeletal dysplasias.