Markedly elevated serum biotinidase activity may indicate glycogen storage disease type Ia.

We report two children who presented with symptoms suggestive of biotinidase deficiency. Rather than deficiency, markedly elevated serum biotinidase activities were found. Based upon literature reports of elevated biotinidase activities in children with glycogen storage disease (GSD) type Ia, we considered the latter in our differential diagnosis and subsequently confirmed GSD type Ia in both patients by enzymatic testing. GSD type Ia should be considered in children with markedly elevated serum biotinidase activity.

Supracondylar osteotomy of the femur with use of compression. Osteosynthesis with a malleable implant.

BACKGROUND: The goal of treatment of a valgus deformity of the knee that is secondary to osteoarthritis of the lateral compartment is to obtain axial correction of the malalignment of the extremity. Osteosynthesis of the osteotomized femur with use of internal fixation and a stiff implant has not been as successful as expected. We evaluated the accuracy and maintenance of correction and the stability of fixation with a malleable plate after a supracondylar osteotomy of the distal aspect of the femur that was performed to correct a valgus deformity of the knee. METHODS: We performed an incomplete oblique osteotomy of the distal aspect of the femur in nineteen patients (twenty-one knees) and stabilized the osteotomy site with a malleable semitubular plate, which was bent to form an angled plate, and lag-screws. Postoperatively, the patients were immediately encouraged to walk, with partial weight-bearing on the affected extremity. The mean age of the patients was fifty-seven years (range, thirty-nine to seventy-one years), and the mean duration of follow-up was five years (range, two to twelve years). RESULTS: In seventeen knees, the osteosynthesis withstood the mechanical loading that occurred during the postoperative functional rehabilitation program. Prolonged use of crutches or immobilization, or both, was necessary after the operation in three knees. The osteosynthesis failed in one knee. The loss of correction in eighteen knees, after bone-healing, averaged 1.7 degrees (range, 0 to 4 degrees). CONCLUSIONS: Our method of achieving osteosynthesis is based on the concept that inherent endogenous stability mechanisms can be mobilized by circumferentially compressing the two cortical tubes with the cut ends congruently apposed to each other. We believe that our technique provides an alternative to osteosynthesis with use of a stiff implant such as a fixed-angle blade-plate device.

Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: report of five new cases and review.

The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

Bilateral calcaneal fracture in childhood. Case report and review of the literature.

Calcaneal fractures in young children are rare. Bilateral calcaneal fractures in this age group are exceptional. In the literature only 4 cases of bilateral calcaneal fractures have been reported, and the youngest patient was 6 years old (range 6-17 years). Jonasch estimated that calcaneal fractures accounted for 0.005% of all fractures before the age of 15, in contrast to 1%-2% in adults. This is confirmed by other studies. It is not unlikely that the incidence is indeed higher because the joint involvement in childhood injuries is often subtle, and the fracture can easily be overlooked on initial X-ray examination. We survey the literature and report the case of a 5-year-old boy who sustained bilateral calcaneal fractures and an additional fracture of the neck of the talus on one side, a combination which to our knowledge has never been described before.

[Fracture of the odontoid process in primary myelopathy. Report of a case]. / Densfraktur mit primärer Myelopathie. Fallbericht.

Fractures of the odontoid are reported to contribute in 15% to cervical spine fractures. The clinical findings range between no symptoms at all and sudden death. Neurological deficits are seen in 6 to 25% of these patients. The overall mortality in this group is 3 to 8%. Fractures of the odontoid process combined with primary myelopathy has been reported seldom. We describe a traumatic fracture of the odontoid process with primary myelopathy, the chosen therapy and the follow-up.

The value of percutaneous transpedicular vertebral bone biopsies for histologic examination. Results of an experimental histopathologic study comparing two biopsy needles.

STUDY DESIGN: A 3.5-mm trephine was designed to overcome difficulties encountered in the histologic evaluation of vertebral bone samples obtained with a 2-mm trephine. OBJECTIVES: To compare the 3.5-mm trephine with the 2-mm trephine. SUMMARY OF BACKGROUND DATA: A review of results obtained with a 2-mm trephine showed that histologic examination of vertebral bone cores was disturbed by artifacts in 32 of 70 cases (46%). Although tissue diagnosis was possible from 61 samples, only 36 (51%) bone cores yielded a secure diagnosis. METHODS: Transpedicular bone cores were obtained from the bodies of 54 fresh cadaver vertebrae with both trephines. In each vertebra, the 2-mm trephine was used on one side, and the 3.5-mm trephine was used on the other side. Longitudinal sections were prepared and examined macroscopically for length and breakages and microscopically for trabeculae, marrow, and artifacts. Each sample was graded for its value for histologic examination. RESULTS: Significant differences were found between the two trephines for all criteria evaluated. Of 54 samples taken with the 2-mm trephine, 13 (24%) were graded "good," compared with 45 (83%) from the 3.5-mm trephine. Twelve (22%) "bad" samples were taken from the 2-mm trephine compared with three (6%) "bad" samples taken from the 3.5-mm trephine. CONCLUSIONS: The 2-mm trephine does not provide suitable bone cores for histologic examination, whereas samples obtained with the 3.5-mm trephine are suitable.

Epidermolysis bullosa acquisita induced by GM-CSF: a role for eosinophils in treatment-related toxicity.

A patient treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) developed eosinophilia and epidermolysis bullosa acquisita. The bullae were subepidermal, and filled with an inflammatory infiltrate composed predominantly of eosinophils. Immunofluorescence studies disclosed linear deposition of IgG, IgA and C3 at the basement membrane zone and immunoelectron microscopy demonstrated antibody deposition in the lamina densa and sublamina densa region; however, the patient's serum did not contain circulating antibody to basement membrane zone antigens. Staining with monoclonal antibodies revealed dense deposits of both eosinophil peroxidase and eosinophil major basic protein at the dermal-epidermal junction. The eosinophilia and skin lesions resolved upon discontinuation of GM-CSF. This case provides evidence for two hypotheses: (1) GM-CSF induced proliferation and activation of eosinophils may contribute to some of the toxicities of GM-CSF treatment, and (2) activated granulocytes, including eosinophils, may mediate blister formation in epidermolysis bullosa acquisita.

A structurally abnormal erythropoietin receptor gene in a human erythroleukemia cell line.

Restriction endonuclease mapping demonstrates a 3' end deletion of one erythropoietin receptor (EpoR) gene in TF-1 cells, a human erythroleukemia cell line that overexpresses the EpoR and proliferates in response to erythropoietin (Epo). EpoR mRNA transcripts are highly abundant and normal in size. These findings raise interesting questions about the possible role of this EpoR gene abnormality in the pathogenesis of the erythroleukemia from which this cell line was derived. This is the first report of an abnormal human erythropoietin receptor gene.

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure.

A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.

Identification of the origin of centromeres in whole-arm translocations using fluorescent in situ hybridization with alpha-satellite DNA probes.

We detected 2 patients with whole-arm translocations resulting in a derivative chromosome consisting of 18q and 21q. Because the breakpoints were near the centromere, classical cytogenetic techniques could not determine the centromeric origin of the derivative chromosomes. Using nonradioactive in situ hybridization with a chromosome 18 alpha-satellite DNA probe (D18Z1), the centromeres in the abnormal chromosomes were determined to be from chromosome 18. The abnormality in one patient resulted in monosomy 18p with a karyotype 45,XX, -18, -21, + der(18)t(18;21) (p11;q11)mat complement. The second patient with a 46,XX, -21, + der(18)t(18;21)(p11;q11) de novo karyotype had complete trisomy of 18q. In both cases the appropriate phenotype was observed.

Posterior stabilization of the cervical spine with hook plates.

Hook-plate fixation is designed for posterior cervical stabilization from C2 to C7. Indications remain the same as for standard posterior fixations. The prime indications are discoligamentous injuries. The plates are hooked under the lower laminas and attached to the articular masses of the upper vertebra by oblique screws. An H-graft is placed between the spinous processes. The vertebrae are compressed together by the plates at three points, the facet joints, and graft. The resulting pre-stressed system is stable in all directions. A protocol for safe reduction of cervical dislocations is observed. Of 70 patients treated from 1979 to 1986, 51 were examined 12-54 months after surgery. All fusions consolidated. Two neurologic complications not attributable to the fixation occurred. Other major complications were not seen.

Overdistraction: a hazard of skull traction in the management of acute injuries of the cervical spine.

In acute cervical spine trauma, skull traction is used to reduce a dislocation or fracture dislocation, to immobilize an unstable lesion until definitive treatment (operative or conservative) is possible or, more rarely, as a definitive treatment until healing occurs. This method may be dangerous when an unstable lesion is accidentally overdistracted. A few cases have been reported in the literature, some with neurological complications. We report five cases in which overdistraction was seen. Two hangman's fractures were overdistracted. One of the two patients developed a Cheyne-Stokes breathing pattern during traction which resolved after the weight was reduced. Furthermore, two hyperextension/distraction injuries (C4/5 and C6/7) and one bilateral C5/6 fracture dislocation were overdistracted without neurological deterioration. Occipitocervical dislocations, fractures of the odontoid process, hangman's fractures, hyperextension/distraction injuries and bilateral dislocations or fracture dislocations may present disruption of both the anterior and posterior elements. Therefore, these injuries are specially vulnerable to overdistraction when skull traction is used. To prevent accidental overdistraction during skull traction, we recommend the use of less weight than is generally proposed in the literature. To reduce a dislocation, we start traction weight at 2 kg and slowly increase it under continuous neurological and radiological monitoring until reduction is completed. Traction of 5-7 kg is usually sufficient; however, heavier traction may occasionally be necessary. After reduction is completed, traction is reduced to 2 kg. This weight is sufficient to immobilize a lesion until definitive treatment is possible. Inadvertent rotation may be prevented by placing sandbags on both sides of the head.

Reliability of an observational system used to monitor behavior in a mental health residential treatment unit.

This article discusses the importance of carefully monitoring and documenting patient behavior in mental health inpatient programs. A structured behavioral observation system is presented along with data evaluating its reliability. This Unit Coverage system is shown to have acceptable reliability, as reflected in an obtained interobserver agreement of 86.2%, corrected for chance.

Infantile hypophosphatasia: autosomal recessive transmission to two related sibships.

Hypophosphatasia, a rare heritable form of rickets/osteomalacia, is characterized by deficient activity of the tissue nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP). Signs may be present prenatally or not until late adult life. Although the infantile form of hypophosphatasia has usually been categorized as an autosomal recessive (AR) disorder, several studies suggest that childhood cases are the consequence of either AR or autosomal dominant (AD) inheritance and adult cases are primarily AD. Eastman and Bixler (J Craniofac Genet Dev Biol 3:213-234, 1983) propose that all cases of hypophosphatasia may reflect AD inheritance with 85% penetrance and homozygous lethality. We report on 3 patients with hypophosphatasia in a black family, first manifested clinically during infancy, where the pattern of inheritance for each is consistent with AR transmission. Two were brothers who died from the disorder. The other patient, a cousin, presented with classic stigmata of hypophosphatasia during infancy, but is now age 5 1/2 years and has had a much milder clinical course. Although consanguinity is absent, the maternal grandmothers are sibs as are the maternal grandfathers and the paternal grandmothers. The family history is otherwise negative for skeletal or dental disease. Laboratory and radiographic results are consistent with heterozygosity in each parent. Fibroblast ALP activity is less than 1% normal in all 3 patients with no complementation observed in heterokaryon analysis. Accordingly, the genetic defects appear to be identical in all 3 patients. Our findings show that infantile hypophosphatasia may be inherited as an AR condition where there is variable expressivity and that homozygosity or compound heterozygosity, as may be the case in this family, is not necessarily lethal.

Inborn errors of metabolism of acute onset in infancy.

The detection of more than 70 inborn errors that are brought to medical attention acutely in the neonate and infant relies on the primary clinician's familiarity with the symptoms with which they present. After consideration, appropriate initial screening laboratory tests can be obtained. Certain conditions, such as metabolic acidosis and/or hyperammonemia, with or without hypoglycemia, will signal the need for further consultation with metabolic specialists, as well as for more specific tests. With the information described in this paper, the primary clinician should be able to be the first effective evaluator among many in a process resulting in a precise diagnosis of these inherited conditions. Treatment is available, in both the acute and chronic phases, for many of these disorders. In virtually all of these conditions, for patients in whom the treatment is incomplete or in whom the disorder is lethal, adequate study should make prenatal diagnosis possible. The recurrence risk of at least 1 in 4 makes the recognition of these conditions important. Thoughtful genetic counseling is essential.