Pyridoxine-Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL Gene

Abstract

Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism caused by a number of loss-of-function mutations in the ALPL gene. It is characterized by defective bone and tooth mineralisation associated with low serum and bone alkaline phosphatase activity. The clinical presentation of this disease is extremely variable. For this reason, the diagnosis can be difficult and is often missed out or delayed. Hypophosphatasia is classified into subtypes based on the age of onset and clinical features. The clinical severity is associated with the age at diagnosis and the lack of tissue-nonspecific alkaline phosphatase activity; the severe forms of hypophosphatasia are primarily perinatal and infantile forms. Severe forms may present with many neurological problems such as seizures, hypotonia, irritability. Herein, we report the case of an infantile hypophosphatasia patient who presented with pyridoxine-responsive seizures and a novel homozygous mutation in the ALPL gene was detected. There is a limited number of hypophosphatasia patients with pyridoxine-responsive seizures in the literature, so early diagnosis of infantile hypophosphatasia in the clinically compatible patients allows more effective postnatal care/management and genetic counseling for further pregnancies.

Figure 1. Facial phenotype of the patient showing flattened facial appearance, broad forehead, flattened nasal bridge, bilateral low-set ears, short neck, and narrow thorax

Figure 2. Radiographic imaging of the patient showing distorted trabeculation, reduced mineralization, metaphyseal irregularities, cupping, diaphyseal shortening, shortness of the right humerus, ulna, and radius

Figure 3. Diagram showing homozygous deletion (c.799_840delCACTTC) on ALPL gene of the proband (a). Electropherograms of father (b) and mother (c) confirming heterozygous presence of the same mutation that was detected in the proband