Table 1 Metabolic rare disesases
From: Bone fragility in patients affected by congenital diseases non skeletal in origin
Disease | OMIM phenotype number | OMIM gene/locus number | Gene | Chromosome location | Bone phenotype (specific signs and symptoms) | Bone biochemical markers |
|---|---|---|---|---|---|---|
A. Lysosomal storage diseases | ||||||
Aspartylglucosa-minuria | 208400 | 613228 | AGA | 4q34.3 | Short stature, delayed skeletal maturation, kyphosis, scoliosis, flattening and anterior breaking of vertebral bodies, spondylolysis, spondylolisthesis, joint laxity, bursitis, pathologic fractures, mild dysostosis multiplex, and loss of weight (adult) | NR |
Gaucher disease, type I | 230800 | 606463 | GBA | 1q22 | Gaucher cells in the bone marrow, growth retardation, osteolytic lesions, cortical thinning, osteonecrosis, osteosclerosis, bone crises, bone pain, osteopenia, osteoporosis, pathologic fractures, rarely acute osteomyelitis, vertebral compressions, avascular necrosis of femoral head, and erlenmeyer flask' deformity of the femurs | Markers of bone formation in treatment-naïve patients: N or low Markers of bone resorption: N or high. |
GM1-gangliosidosis, type III | 230650 | 611458 | GLB1 | 3p22.3 | Short stature, mild platyspondyly, bone dysplasia, mild anterior breaking of lumbar vertebrae, kyphosis, scoliosis, hypoplastic acetabulae, flat femoral heads, and flared iliac wings. | NR |
Scheie syndrome: mucopolysaccharidosis type IS; MPS1-S | 607016 | 607016 | IDUA | 4p16.3 | Joint contractures, dysostosis multiplex, mild (in some patients), lumbar-sacral spondylolisthesis, genu valgum, carpal tunnel syndrome, claw-hand deformity, and pes cavus | NR |
Hurler- scheie syndrome: mucopolysaccharidosis IH/S | 607015 | 252800 | IDUA | 4p16.3 | Short stature, dysostosis multiplex, joint stiffness, joint contractures, osteoporosis, scoliosis, kyphosis, progressive lumbar gibbus, and flat femurs with short metaphyses | High serum BSAP and OCN High urine DPD Low serum 25 (OH) D3 |
Mucopolysaccharidosi type II; MPS2 (hunter syndrome) | 309900 | 300823 | IDS | Xq28 | Mild dwarfism, adult height 120-150 cm, scaphocephaly, macrocephaly, stiff joints, joint pain, restrictive joint range of motion, hip dysplasia, arthropathy, dysostosis multiplex, osteoporosis, kyphosis, flexion contractures, claw hand, and pes cavus. | High serum BSAP and OCN High urine DPD Low serum 25 (OH) D3 |
Mucopolysaccharidosis type IVA; MPS4A (morquio syndrome A) | 253000 | 612222 | GALNS | 16q24.3 | Short stature (adult height 82 to 115 cm), short-trunked dwarfism, pectus carinatum, osteoporosis, platyspondyly, odontoid hypoplasia, cervical subluxation, kyphosis, ovoid vertebral bodies, hyperlordosis, scoliosis, coxa valga, constricted iliac wings, laxity of wrist joints, genu valgum, ulnar deviation of the wrist, epiphyseal deformities of tubular bones, and widened metaphyses. | NR |
Mucopolysaccharidosis type IVB; MPS4B (morquio syndrome B) | 253010 | 611458 | GLB1 | 3p22.3 | Short stature (adult height 82-115 cm), short-trunked dwarfism, osteoporosis, platyspondyly, odontoid hypoplasia, cervical subluxation, kyphosis, hyperlordosis, scoliosis, ovoid vertebral bodies, coxa valga, constricted iliac wings, joint laxity, severe genu valgum, ulnar deviation of the wrist, epiphyseal deformities of tubular bones, and widened metaphyses. | NR |
Multiple sulfatase deficiency; MSD | 272200 | 607939 | SUMF1 | 3p26.1 | Short stature, dysostosis multiplex, hypoplastic vertebral bodies, broad thumbs, and broad index fingers. | NR |
Mucolipidosis II alpha/beta (I-cell disease; ICD) | 252500 | 607840 | GNPTAB | 12q23.2 | Birth length less than normal, deceleration of linear growth during first year, marked growth retardation, moderate joint limitation, scapular hypoplasia, dysostosis multiplex, osteopenia in early infancy, pathologic fractures, thickened cranium, craniosynostosis, dorsolumbar kyphosis, atlantoaxial dislocation, ovoid vertebral bodies, narrowness of interpediculate distances in lower thoracic regions, hypoplastic odontoid process, beaking of vertebral bodies T12-L3, lumbar gibbus, flared iliac wings, horizontal acetabular roofs, supra-acetabular constriction, hip dislocation, irregular contours of pubis and ischium, cortical bone erosion (especially proximal femora), long bone shortening, widened metaphyses, varus deformity of humeral neck, tilted distal ends of radius and ulna, broadening of wrist, brachyphalangia, hypoplasia of carpal bones, conical bullet-shaped distal ends of phalanges, claw-hand deformities, and talipes equinovarus | NR |
Mucolipidosis III alpha/beta (pseudo-hurler polydystrophy) | 252600 | 607840 | GNPTAB | 12q23.2 | Short stature, short and thick clavicles, wide and slightly short ribs, dysostosis multiplex, scoliosis, absence of dens, vertebral beaking, flaring of iliac wings, shallow acetabular fossae, shoulder stiffness, broad metaphyses, short long bones, hand stiffness, claw-hand deformities, carpal tunnel syndrome, soft tissue swelling of interphalangeal joints, and small and irregular carpal bones. | NR |
Mucolipidosis II alpha/beta (I-cell disease; ICD) | 252500 | 607840 | GNPTAB | 12q23.2 | Birth length less than normal, deceleration of linear growth during first year, marked growth retardation, moderate joint limitation, scapular hypoplasia, dysostosis multiplex, osteopenia in early infancy, pathologic fractures, thickened cranium, craniosynostosis, dorsolumbar kyphosis, atlantoaxial dislocation, ovoid vertebral bodies, narrowness of interpediculate distances in lower thoracic regions, hypoplastic odontoid process, beaking of vertebral bodies T12-L3, lumbar gibbus, flared iliac wings, horizontal acetabular roofs, supra-acetabular constriction, hip dislocation, irregular contours of pubis and ischium, cortical bone erosion (especially proximal femora), long bone shortening, widened metaphyses, varus deformity of humeral neck, tilted distal ends of radius and ulna, broadening of wrist, brachyphalangia, hypoplasia of carpal bones, conical bullet-shaped distal ends of phalanges, claw-hand deformities, and talipes equinovarus | NR |
Mucolipidosis III alpha/beta (pseudo-hurler polydystrophy) | 252600 | 607840 | GNPTAB | 12q23.2 | Short stature, short and thick clavicles, wide and slightly short ribs, dysostosis multiplex, scoliosis, absence of dens, vertebral beaking, flaring of iliac wings, shallow acetabular fossae, shoulder stiffness, broad metaphyses, short long bones, hand stiffness, claw-hand deformities, carpal tunnel syndrome, soft tissue swelling of interphalangeal joints, and small and irregular carpal bones. | NR |
Fabry disease | 301500 | 301644 | #301500 | Xq22.1 | Hands with limited extension of terminal joints, osteoporosis, non–traumatic fractures | High serum PTH and OCN |
B. Disorders of sulfur metabolism | ||||||
Homocystinuria (due to cystathionine beta-synthase deficiency) | 236200 | 613381 | CBS | 21q22.3 | Normal to tall stature, generalized osteoporosis, biconcave 'codfish' vertebrae, kyphoscoliosis, dolichostenomelia, arachnodactyly, and limited joint mobility | NR |
C. Disorders of tyrosine pathway | ||||||
Alkaptonuria | 203500 | 607474 | HGD | 3q13.33 | Height loss secondary to spinal changes, joint ochronosis and subsequent osteoarthritis (ochronotic pigmentation of fibrous tissues including cartilage, tendons, ligaments, intervetebral disks, ochronotic arthritis and arthropathy), chronic joint pain, back pain, kyphosis, degeneration of intervertebral disks, fusion of vertebral bodies, osteopenia, osteoporosis, fractures, spondylosis, peripheral arthropathy, decreased lumbar flexion and tendon and ligament ruptures | High serum NTx and BSAP |
Phenylketonuria | 261600 | 612349 | PAH | 12q23.2 | Low bone mineral density | In children: low serum BSAP, OCN, and P1NP In adults: high urine PYR, serum CTX, and NTx and low serum OPG |