Eino Marttinen

The Spine in Diastrophic Dysplasia

Diastrophic dysplasia is an autosomal recessive disorder of the skeleton, characterized by disproportionate short stature, generalized joint deformities, club feet, deformed ear pinnae, and, frequently, spinal deformity and cleft palate. Diastrophic dysplasia is more common in Finland than elsewhere. We studied 101 patients with an age range from newborns to 79 years to find out the frequency and type of spinal deformities, the early signs of progressive cases, and to follow the natural history of the disease. In the follow-up study, 17 patients were under 10 years, 21 under 21 years, and 63 over 21 years of age. One-third of the patients had cervical kyphosis; in the most severe case the kyphosis was 180° and led to quadriplegia during anesthesia. In three patients, cervical kyphosis resolved spontaneously before the age of 5 years. The overall frequency of scoliosis was 37%; 49% in women and 22% in men. Only 13 patients had curves greater than 50°; these curves constituted distinct rotation at the apex from the early evolution of the curve. The early signs of severe curves were detectable at the age of 2 to 4 years. Only two patients were operated on because of scoliosis; one with fusion in situ and the other instrumented with the pediatric Cotrel-Dubousset instrumentation. Three patients had a brace, which did not prevent the progression of the curve. Symptoms referring to a narrow spinal canal were registered in four patients, two of which were operated on; a lumbar posterior decompressive procedure was made at adult age.

Growth after renal transplantation in infancy or early childhood.

Abstract Forty-one children <5 years of age at kidney transplantation (TX) were investigated for growth, bone age, and renal function up to 7 years (n=26) after TX. All children received triple immunosuppression, including alternate-day corticosteroid treatment. Catch-up growth was seen in 81% of 30 children without growth hormone (GH) treatment. Children <2 years of age without GH had a mean height standard deviation score (hSDS) of –1.1±0.8 at TX and –1.1±0.5 at 7 years; children between 2 and 5 years improved their hSDS from –1.9±0.9 to –0.4±0.8 (P<0.0001). The hSDS at TX correlated inversely with the ΔhSDS from TX to 7 years (r=–0.80, P=0.0002). Glomerular filtrations rate (GFR) at 5 years post TX correlated with the subsequent growth rate from 5 to 7 years TX (r=0.58, P=0.01). Catch-up growth was seen in all 11 children receiving GH. Their mean hSDS improved from –2.5±0.9 to –1.1±0.9 (P<0.0001). In the majority of children receiving a kidney graft in early life, triple immunosuppression with alternate-day steroids can ensure catch-up growth. In children <5 years of age at TX, growth is predicted better by the degree of stunting than by age.

Cervical kyphosis in diastrophic dysplasia.

STUDY DESIGN An evaluation of cervical kyphosis in diastrophic dysplasia from newborn to adult life. OBJECTIVES To discover the prevalence and natural history of cervical kyphosis in diastrophic dysplasia. SUMMARY OF BACKGROUND DATA Typical findings in this rare skeletal dysplasia are sport-limbed short stature, multiple joint contractures, early degeneration of joints, and spinal deformities such as cervical kyphosis, scoliosis, and exaggerated lumbar lordosis. In diastrophic dysplasia, spontaneous resolution of cervical kyphosis has been reported, but so have severe forms causing medullar compression leading to quadriplegia and death. The prevalence and clinical outcome of the kyphosis are not known. METHODS The radiographic natural history of the cervical spine was studied in 120 patients. They varied in age from newborns to 63-year-olds. The average follow-up time in 26 living patients with cervical kyphosis was 10.0 years. RESULTS Midcervical kyphosis was noted in 29 patients (24%) in their first radiograph. In 25 patients, the first radiographs were taken before the age of 18 months, and 24 of these patients (96%) had cervical kyphosis. The most severe case was that of a 32-year-old patient with a 165 degrees kyphosis. In the 24 patients, the kyphosis resolved spontaneously at an average age of 7.1 years. Three patients with a severe kyphosis died; one patient is alive. One patient, a 4-year-old child has mild resolving deformity. CONCLUSIONS Cervical kyphosis in diastrophic dysplasia usually is shown at the time of birth. It resolves spontaneously during growth and seldom needs treatment. Careful follow-up study and treatment, if necessary, are important tools for avoiding the neurologic problems and fatal outcome.

Cohen syndrome: evaluation of its cardiac, endocrine and radiological features

Cohen syndrome (MIM no. 216550) is an autosomal recessive disorder with a typical clinical picture. Since the first report, most publications have represented single case reports. In this study, our aim was to describe cardiac, endocrine and radiological abnormalities in 22 Cohen patients of Finnish descent. Detailed investigations of the heart revealed the anatomy of the heart to be normal with no evidence for clinically significant mitral prolapse. However, a decreased left ventricular function with advancing age was identified. No significant endocrine abnormalities were found at the examination of pituitary, adrenal and thyroid function. The height was either normal or patients were moderately short (mean height standard deviation score (SDS) −2) at all ages, associated, however, often with the marked kyphosis. Truncal obesity was seen in 4/22 patients. X‐rays of the chest, lumbar and thoracic spine, long bones, ankles and metacarpophalangeal pattern profiles revealed kyphosis, scoliosis and calcaneo planovalgus as common features. Fingers of these patients were slender but short with a characteristic metacarpophalangeal pattern profile.

Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients.

Cartilage-hair hypoplasia is a metaphyseal chondrodysplasia with short-limbed short stature. In childhood radiographs the metaphyseal regions of the tubular bones are widened, scalloped and irregularly sclerotic. We have analyzed radiological characteristics and skeletal growth in 149 radiographic surveys of 82 Finnish patients. All extremity long bones were affected and short for age. The growth failure was progressive. In the adults the median relative lengths were for the humerus −6.3 SD, radius −8.6 SD, ulna −6.7 SD, femur −9.7 SD, tibia −8.7 SD, and fibula −6.8 SD. The severity of the metaphyseal changes correlated with the degree of the growth failure. The skeletal age was markedly retarded in 14% of the patients. Caudal widening of the interpediculate distance in the lumbar spine was observed in 90% of the patients, but it tended to be less than normal. The sagittal diameter of the spinal canal was normal in the cervical region but decreased in the lumbar region. Mild scoliosis was observed in one-fourth of the patients, and its incidence increased with age. Lumbar lordosis was moderately increased. Thoracic deformity was observed in 82% of the patients. The relative interorbital distance was increased with the median of +2.2 SD in the adults.

Magnetic Resonance Imaging Findings of the Pancreas in Patients with Shwachman-Diamond Syndrome and Mutations in the SBDS Gene

Pancreatic MRI was evaluated in 14 patients with a clinical diagnosis of Shwachman-Diamond syndrome, and the findings were correlated with Shwachman-Bodian-Diamond gene (SBDS) genotype. The findings suggest that patients with mutations in the SBDS gene have a characteristic magnetic resonance imaging pattern of fat-replaced pancreas and that SBDS mutations are unlikely in patients without this pattern.

Very low rate of type I collagen synthesis and degradation in newly diagnosed children with acute lymphoblastic leukemia

In children with acute lymphoblastic leukemia (ALL), the metabolism of type I collagen, the major collagen of bones, may be changed at diagnosis and during early chemotherapy. In the present study, bone formation and degradation rates were evaluated longitudinally in 35 children with ALL, using two serum markers of bone collagen formation: the amino-terminal (PINP) and carboxyterminal (PICP) propeptides; and a marker of degradation: the carboxyterminal telopeptide of type I collagen (ICTP). These serum markers were determined at diagnosis, during induction treatment (at 1, 4, and 6 weeks), and during consolidation treatment (at 8 and 12 weeks). The changes in the serum markers suggested that, at diagnosis, type I collagen turnover (i.e., both synthesis and degradation) was remarkably low. The median serum levels of PINP, PICP, and ICTP were -2.6 SDS (standard deviation score), -1.5 SDS, and -2.5 SDS, respectively. The PICP and PINP levels declined further during the first week of therapy (p < 0.001), whereas the ICTP levels had risen by end of the induction phase (p < 0.05). By the end of the 12 week interval, the concentrations of the formation and degradation markers had returned to normal (p < 0.01). Our findings suggest that ALL is accompanied by low turnover of bone collagen. The abnormalities are at first aggravated, but then corrected, by treatment.

Late urologic sequelae after surgery for congenital sacrococcygeal teratoma

Forty-five patients treated for congenital sacrococcygeal teratoma were examined for late urologic outcome. The follow-up ranged from 4 to 42 (median 22) years. Only 8 patients experienced subjective urinary complaints. Sonography of the urinary tract revealed unilateral hydronephrosis in 2 patients, an ectopic kidney in 1, and a severely scarred kidney in 1; 1 patient had asymptomatic bacteriuria. Urodynamic screening using uroflowmetry was abnormal in 35 patients (78%). The risk of significant postoperative complications and subsequent late sequelae was greatest among patients with intrapelvic extension of the primary tumor.

Metabolic Control and Growth during Exclusive Growth Hormone Treatment in X-Linked Hypophosphatemic Rickets

Background: GH may improve phosphate balance and height in X-linked hypophosphatemic rickets (XLH). This study evaluated the impact of exclusive rhGH therapy on phosphate homeostasis and growth. Methods: Ten children (median age 12.2 years) with XLH were included in a 12-month trial with GH. Conventional treatment was discontinued 1 month prior GH (0.033 mg/kg/day); 1α-hydroxyvitamin D was added at 6 months and oral phosphate at 12 months, when GH was discontinued. Patients were followed 1–3 monthly until 18 months for clinical, biochemical and radiographic parameters. Results: Serum phosphate Z-score increased significantly from baseline at 6 months (p = 0.005) and 9 months (p = 0.009) but returned to baseline by 12 months. Serum 1,25-dihydroxyvitamin D also increased significantly. Parathyroid function normalized. The median height Z-score was –2.2 (–2.7 to +0.4) at GH onset and –1.7 (–2.3 to +0.3) at 12 months. One patient showed a significant increase in radiographic rickets activity and 3 patients aggravation of lower limb deformity; the others showed no changes or improvement in these parameters. Conclusions: GH treatment improved serum phosphate and 1,25-dihydroxyvitamin D, normalized parathyroid function and improved longitudinal growth in XLH. It may however aggravate pre-existing skeletal deformities.

The natural history of Shwachman-Diamond syndrome-associated liver disease from childhood to adulthood.

OBJECTIVES In order to characterize the natural course of Shwachman-Diamond syndrome (SDS)-associated hepatopathy we evaluated liver biochemistry and imaging findings, and their evolution with age, in patients with SDS and verified SBDS mutations. STUDY DESIGN Retrospective and cross-sectional liver imaging, biochemical and histologic data of 12 patients (age range 2.1 to 37 years) with SBDS mutations were analyzed. Hepatic volume and parenchymal structure were determined from magnetic resonance imaging data. RESULTS Hepatomegaly and aminotransaminase elevation was observed in most of the patients with SDS at an early age; values normalized by age 5 years and remained normal over extended follow-up. Mild to moderate serum bile acid elevation was noted in 7 patients (58%). On magnetic resonance imaging, no patients (n = 11) had evidence of hepatic steatosis, cirrhosis, or fibrosis. Three middle-aged patients had hepatic microcysts. CONCLUSIONS SDS-associated hepatopathy has overall good prognosis. No major hepatic abnormalities developed during extended follow-up to adulthood. Mild cholestasis in follow-up even after normalization of transaminase levels may reflect primary alterations in liver metabolism in SDS.