CASO CLÍNICO

Childhood with myopathy: clinical report with recent update

Silva I 1, Castelão W 1, Mateus M 1, Branco JC 2,1

ACTA REUMATOL PORT. 2012;37:92-96

AbstrAct chondrocytes, osteoblasts and odontoblasts, and then followed by the propagation of the hydroxyapatite into Hypophosphatasia is a rare genetic disease with low tis - the extracellular matrix and between collagen fibrils) 1. sue nonspeficic alkaline phosphatase activity Inorganic pyrophosphate (PPi) inhibits hydroxyapatite (TNSALP), due to ALPL gene mutation. There are 6 formation. Tissue-nonspecific alkaline phosphatase clinical forms. Childhood form is caractheri zed by short (TNSALP) hydrolyses PPi into phosphate (Pi), and this stature, premature loss of decidous teeth and diffuse ba lance is fundamental to the mineralization 1-3 . There bone pain associated with a pathological bone fracture are 4 isomeres of the alkaline phosphatase (AP): in the past. Laboratory findings present low serum le- TNSALP, intestinal, placenta and germ cell. All of them vel of alkaline phosphatase and high levels of serum are homodimeric ectoproteins anchored to the plasma and urinary extracelular metabolytes. It is described a membrane by a phosphatidylinositol glycan (PIG) moie - case report of a 34 years old woman with previous diag- ty. TNSALP clives PPi, pyridoxal-5-phosphate (PLP- an nosis of childhood hypophosphatasia, caryotype activated form of vitamin B 6) and phosphoetha- 46,XX, and molecular screening for the gene ALPL with nolamine (PEA) in its dimeric form at physiologic pH, a c.1426>A p.E476K mutation, who complained of and whose expression changes according to the age 2. proximal muscular weakness intensified with the cold Hyphosphatasia (HP) is a rare genetic disease caused weather, exercise, and a waddling gait. The elec - by a low activity of the TNSALP with defective bone tromyography was compatible with myopathy but the and teeth mineralization 4. Clinical expression varies muscle biopsy was normal. The serum crea tine kinase with the type of mutation and the age of diagnosis 1-4 . levels were normal, as well as the others muscle en - The incidence of the severe forms is estimated in zymes. Clinical and laboratory/ /imaging dissociation is 1/100000 (USA), but because its incomplete pene - frequent in other metabo lic bone diseases as osteoma - trance it is difficult to know the correct prevalence. lacia. The rarity of this case of childhood hypophos - ALPL , the gene encoding TNSALP, presents more than phatasia with “ de novo” non-progressive myopathy of 190 mutations, some of them target specific popula - the lower limbs, justified a case report with literature re - tions or regions 2,4 , and with a good genotype-pheno - vision. type correlation 2,5,6 . There are 6 clinical forms: perina - tal (lethal or benign), infantile, childhood, adult and Keywords: Hypophosphatasia; Myopathy; Alkaline odontohypophosphatasia (Table I) 1-4 . Phosphatase; . The childhood form is characterised by low bone mineral density and unexplained fractures, premature loss of deciduous teeth (beginning with incisors), short IntroductIon stature and delay in walking, bone pain (bone oede - ma), joint pain (condrocalcinosis and osteoarthritis de - Biomineralization is a process by which hydroxyapatite velop with aging), pseu dofracture in the lateral cortex is deposited in the extracellular matrix (first within ma - of the femoral diaphysis (Looser zones), and sometimes trix vesicles that bud from the surface membrane of a waddling gait 2-4 . Specific diagnostic clues are shown in Table I, but screening for mutations in ALPL is es - sential to confirm the diagnosis 4. Childhood form does 1. Serviço de Reumatologia do Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, EPE the differential diagnosis with , osteogenesis 2. Faculdade de Ciências Médicas, Universidade Nova de