Metabolic Conditions Usually Affecting Calcium or Phosphorus Metabolism
Rickets
Rickets is caused by vitamin D deficiency that results in osteomalacia, the delayed or inadequate mineralization of osteoid in mature cortical and spongy bone (5). Rickets
14.7
Types of Osteogenesis Imperfecta
| TYPES OF OSTEOGENESIS IMPERFECTA | SCLERA | GENETIC ANOMALY | SEVERITY | DISTINGUISHING CHARACTERISTICS |
| I | Blue | Reduced Amount of type I collagen | Usually mild Few fractures | Most common form, usually without bony deformities; hearing loss may be main disability |
| II | Blue | Abnormal structure of type I collagen | Most severe, often fatal in perinatal period | Severe respiratory compromise often |
| III | Blue or gray, may fade | Abnormal structure of type I collagen | Severe bone fragility | Progressive long bone deformities; very short stature; may have respiratory insufficiency |
| IV | Blue or gray, may fade | Abnormal structure of type I collagen | Variable, often moderate | Bowing of long bones is usually less severe than in type III |
| V | White | Unknown | Moderate to Severe | Hypertrophic callus; fusion of intraosseous membranes; “meshlike” bone biopsy |
| VI | White | Unknown | Moderate | Extremely rare (8); characteristic bones biopsy with mineralization defect (1) |
| VII | White | Mutation of Cartilage- associated protein (CRTAP) gene | Moderate to lethal | Rhizomelia coxa vara is common; may resemble types II or VI recessive |
| VIII | White | Mutation of LEPRE 1 gene leads to abnormal propyl 3-hydroxylase activity | Severe or fatal (8) | May resemble type II or III; bone is under mineralized; recessive |
is a rare condition in the United States.
However, it may be found in higher numbers in dark-skinned breastfed babies who are unsupplemented and all breastfed babies who themselves and/or their mothers have little to no exposure to the sun on a daily basis. Typically, this becomes problematic after 6 months of age.Clinical Characteristics. The clinical features of nutritional rickets include early-onset craniotabes, rachitic rosary (costochondral junction enlargement), and thickening of the wrists and ankles. As rickets continues, clinical findings include progressive bowing of the legs; poor linear growth; and abnormal serum calcium (ionized calcium is the most accurate test), phosphate, and alkaline phosphatase levels. In severe cases, the baby may have seizures.
Diagnostics. The diagnosis of rickets is made with radiographic demonstration of metaphyseal flaring, cupping, and decreased mineralization of the distal metaphysic, as well as laboratory evidence of elevated alkaline phosphatase.
Treatment. The treatment includes supplementation of vitamin D and/or formula. If left untreated, permanent deformities may ensue.
Mucopolysaccharidoses
Mucopolysaccharidoses are hereditary progressive conditions secondary to the accumulation of the mucopolysaccharides (MPS). The underlying problem is a defect in the degradation of MPS leading to accumulation in lysosomes (vacuoles found in almost all cells) (360). There is marked heterogeneity within each of the groups, and life expectancy for some can reach into the fifth decade (361). In general, the later the clinical onset, the slower the clinical picture (360,362).
Clinical Characteristics. Typically, the facial features are coarse. Dwarfism is present to some degree in all these entities. Odontoid hypoplasia can be serious and lead to tetraplegia. Atlantoaxial instability frequently requires fusion, as it is a major complication of this condition, causing spinal cord compression with resulting tetraplegia. Fingers are short and stubby, and hands are wide. Carpal tunnel syndrome (CTS) is common. Typically, the presenting complaint for CTS is difficulty with fine motor tasks, not pain (6). Progressive spasticity and mental deterioration eventually occurs in most types.
Kyphosis can appear early and is usually marked. Blindness may result from optic atrophy. Corneal clouding is a common finding in MPS (362). Deafness may occur as well.Specific Types. Mucopolysaccharidoses are usually divided into six groups. In MPS I, the most severe form is Hurler's syndrome and the mildest form is Scheie's syndrome (MPS IS). The mode of inheritance is autosomal recessive for all groups except MPS II Hunter's disease, which is X-linked recessive. Type III is Sanfilippo A, B, C, D. This is the most common MPS (362).
Type IV Morquio's disease (mucopolysaccharidosis type IV) is characterized by normal intelligence and gross motor milestones early in life. Over time, gait may progressively worsen with severe genu valgum, ligamentous laxity, severe pes planus, and increased sternal protrusion. The chest deformity can be restrictive and cause cardiorespiratory symptoms (362).
Type VI Maroteaux-Lamy has the facial features typical of MPS; intellect generally remains normal; and obstructive sleep apnea, corneal clouding, and deafness are common. VII Sly type can present as hydrops fetalis, or life expectancy can be into the second decade. There can be a wide variability of cognitive ability.
Rehabilitation. A multidisciplinary approach is essential for management of these highly variable MPS. Specific rehabilitation issues may include hand and wrist bracing in neutral to help avoid carpal tunnel syndrome, leg braces for the lower extremities to help avoid contractures and deformities, and TLSO for the back to help avoid scoliosis. Aids for functional independence are essential.
Medical and Surgical Interventions. Bone marrow transplant (BMT) can alter the severe nature of MPS (360). Enzyme replacement therapy (ERT) is available for MPS I, II, and VI (359) and may be beneficial for type VII as well (362). The ERT does not cross the blood-brain barrier or enter the joint space/cartilage or cornea. Earlier BMT in MPS is thought to have the best possibility of good results. Consent for this treatment is often difficult when the child is doing well. VP shunt can help manage hydrocephalus in type I to help preserve intellectual function (362). Similarly, in type III, VP shunting can help with behavioral changes in some patients. Genetic consultation is important secondary to prolonged life expectancy.
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