from the cerebrovascular circulation to the pelvis.220 FIG 59.4 Magnetic resonance angiogram showing distinctive tortuosity of the head and neck vasculature in a patient with Loeys-Dietz syndrome Homocystinuria Homocystinuria is an autosomal recessive disorder usually due to deficiency of cystathionine synthase, an enzyme needed for the metabolism of methionine Affected patients have a body habitus similar to that of patients with Marfan syndrome, albeit their joints usually demonstrate restricted mobility Cognitive deficits are also common The primary cardiac complication is that of atherosclerotic disease, which often occurs by adolescence Endothelial dysfunction contributes to the arterial complications and produces an increased risk for myocardial infarction.221 Vitamin B6 helps to reduce levels of homocysteine in approximately half of patients, and this, along with supplementation of vitamin B12 and folic acid, forms the mainstay of therapy Neuromuscular Diseases Muscular Dystrophies Duchenne Muscular Dystrophy Duchenne muscular dystrophy is an X-linked recessive disease Because of this, it almost always afflicts males Its incidence in male children is calculated at 13 to 33 per 100,000 live births Since females with Turner syndrome have only one X chromosome, they too can inherit the disease, and it is seen rarely in this setting The disease is due to a defect in the gene encoding dystrophin Dystrophin helps to form a complex that stabilizes the sarcolemmal membrane during contraction Although the exact mechanism for muscle degeneration has not been elucidated, abnormal nitric oxide regulation, abnormal sarcolemmal fragility, and increased susceptibility to oxidative stress are felt to play important roles.222 The earliest symptoms are clumsiness in walking, a tendency to fall, and the inability to run Those with the disease also have difficulty in climbing stairs and getting up from the floor Clinical onset is usually manifest before 4 years of age, and the diagnosis is usually made around 6 years of age Deterioration is continuous Most are unable to walk by the age of 10 years Life expectancy is increasing due to improved medical therapies, including nocturnal ventilation, early and aggressive management of cardiomyopathy, and perhaps also the use of steroids.223 Muscular weakness and atrophy initially affect the proximal muscle groups of the upper limbs Leg involvement extends from the quadriceps and gluteal muscles to the anterior tibial muscles Weakness later affects other muscle groups More power is generally retained in the distal muscles Slight facial weakness occurs in the late stages Scapular “winging” is also a later phenomenon Muscular hypertrophy of calves, masticatory muscles, and deltoids is followed by a pseudohypertrophic phase of fatty replacement Tendon reflexes are lost in the weak muscles Contractures of the calves and hip flexor muscles develop around the age of 8 years Contractures appear in the hips, knees, elbows, and wrist, when the patients are confined to wheelchairs Severe spinal and thoracic deformities are seen late in the disease Kyphoscoliosis is common These result from disuse and abnormal posture Generalized decalcification of the bones leads to frequent pathologic fractures