We describe a 5 years-old patient referred to our centre for dysmorphic features and delayed psychomotor development. Negative family history, second child, full-term birth, eutocic delivery, regular growth parameters at birth and neonatal adaptation. Autonomous walking at 20 months with clumsiness; first words at 2 years with dysarthria and dysphagia. Brain MRI and array-CGH were normal. At the neurological examination: perioral hypotonia, sialorrhea, praxic difficulties. At 4 yrs he developed seizures. The EEG showed paroxycal anomalies in the fronto-centro-temporal zones. A diagnosis of focal idiopathic epilepsy was made and therapy with levetiracetam was proposed. At the first evaluation in our centre he showed amimic face, telecanthus, buccal hypotonia, absence of 4 deciduous teeth (he lost the upper central incisors at 2.5 yrs, lower right incisor at 3.5 yrs, upper right canine at 4.9 yrs); enamel dysplasia, prognathism; normal stature, ligamentous hyperlaxity, truncal hypotonia, kyphotic attitude; valgus knees; flat feet; dyspraxia and motor clumsiness. A blood sample showed: alkaline phosphatase (ALP) 81 U/L (normal values:150-315), confirmed in a second blood sample, PEA 58 mmol/ml (normal values: 4-10), B6 vitamin 580 nmol/L (normal values: 29.5-99). A condition of HPP was suspected. Analisis of ALPL gene showed a missense heterozygous mutation c.1172G>A, pathogenetic, compatible with AD-HPP. Renal ultrasound, fundus oculi and skeleton X-ray were normal. Subsequently he lost left upper canine. At the age of 6, because of motor clumsiness, dysarthria, hypotonia, premature tooth loss and epilepsy, although without skeletal involvement, he started therapy with asfotase alfa, which he continued for 3 years. He showed reduction of seizures after the beginning of therapy (seizures disappeared at 7 years), improvement in tone, muscle strength, clumsiness, speech, swallowing; physiological eruption of permanent teeth. The 6 minutes walking test, repeated every six months, showed an improvement in greater distance traveled without falls. He developed side effects in injection sites of therapy: erythematous-edematous lesions with lipodystrophic evolution. Hypophosphatasia is caused by mutations in the gene encoding non-tissue-specific ALP. Biochemical marker is low serum ALP activity, with defective bone and/or tooth mineralization. The serum levels of ALP vary by age with lower values in adults. The severity is variable from fetal death, without mineralization of the skeleton, to isolate dental pathology in adults. Inheritance can be AR (severe forms) or AD (milder). Early recognition is important because asfotase alfa therapy can avoid the onset of functional limitations in adulthood.
21 Sep 2023 - 23 Sep 2023