Objective: We report a hypophosphatasia patient presenting as parkinsonism, characterized by compound heterozygous mutations in ALPL gene.

Background: Hypophosphatasia (HPP) is a rare metabolism disease, caused by loss of function mutation in the ALPL gene. The typical manifestations are commonly considered as bone fractures, tooth loss and other musculoskeletal disorders. Although neurological symptoms can also be seen in patients with HPP, such as fatigue, sleep disorder anxiety and depression, movement disorders are seldomly reported, especially parkinsonism.

Method: Analysis of a patient with HPP who suffered from parkinsonism signs, including tremor and rigidity, through the methodology of neurological examination, neuroimaging, bone mineral density, biochemical and gene detection. The sanger sequencing of DNA was also conducted in patients to verify the genotypes of them.

Results: We reported a 26-year-old man with a 3-year history of parkinsonism, including rest tremor, rigidity and gait disorders, who were suffering from HPP. He was ever diagnosed as depression and anxiety. Neurological examination showed rest tremor in both upper extremities and rigidity of the extremities. Brain magnetic resonance imaging (MRI) did not reveal any abnormalities in the brain. Bone mineral density was in normal range. However, biochemical detection showed that the serum level of alkaline phosphatase was decreased (19U/L, references: 45-125U/L). Gene detection was performed showing two mutations in ALPL gene (ALPL, NM_0004 78(C), exon5, c.407G>A, p.R136H; ALPL, NM_0004 78(C), exon6, c.532T>C, p.Y178H). Further parental verification confirmed that the two mutations were from different chromosomes, indicating that the genotype of the patient was compound heterozygous mutations in ALPL gene. The diagnosis of hypophosphatasia was established. Although the patient responded well to levodopa initially, the parkinsonism manifestations improved less and showed great motor fluctuation as time prolonging.

Conclusion: Hypophosphatasia could also present as parkinsonism, while the effects of levodopa and dopamine receptor agonists seemed limited.

References: [1]. Colazo JM, Hu JR, Dahir KM, Simmons JH. Neurological symptoms in Hypophosphatasia. Osteoporos Int 2018. [2]. Mornet E. Hypophosphatasia. Metabolism 2018; 82:142-155.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hypophosphatasia-presenting-as-parkinsonism-with-compound-heterozygous-mutations-in-alpl-gene/